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PANITUMUMAB

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody and binds to human epidermal growth factor receptors (EGFR) specifically, on both normal and tumor cells. Panitumumab competitively inhibits the binding of ligands for EGFR.

Specific Substances

    1) ABX-EGF
    2) E7.6.3
    3) Panitumumabum
    4) CAS 339177-26-3

Available Forms Sources

    A) FORMS
    1) Panitumumab is available in the US in single-use vials (20 mg/mL): 100 mg/5 mL, 200 mg/10 mL, and 400 mg/20 mL (Prod Info VECTIBIX(R) IV solution, 2008).
    B) USES
    1) Panitumumab is indicated as a single-agent for the treatment of epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens (Prod Info VECTIBIX(R) IV solution, 2008).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Used for the treatment of epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
    B) PHARMACOLOGY: Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody and binds to human EGFR specifically, on both normal and tumor cells. Panitumumab competitively inhibits the binding of ligands for EGFR.
    C) EPIDEMIOLOGY: Overdoses are rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: COMMON: Dermatologic effects develop in most (90%) patients, and include: erythema (65%), acneiform dermatitis (57%), pruritus (57%), nail changes (29%), paronychia (25%), exfoliation (25%), skin fissures (20%), and dry skin (10%). Other adverse effects include: hypomagnesemia (38%), fatigue (26%), abdominal pain (25%), nausea/vomiting (23% and 19%), diarrhea (21%), constipation (21%), and cough (14%). Less common adverse effects include: hyperglycemia, hypokalemia, hypocalcemia, cheilitis, ocular toxicities (e.g. conjunctivitis, ocular hyperemia, increased lacrimation, eye/eyelid irritation, and eyelash growth), thrombophlebitis, bone pain, back pain, asthenia, dyspnea, and infectious complications. Rare, but serious complications include pulmonary fibrosis and infusion-related toxicity (e.g. anaphylactoid reactions, bronchospasm, hypotension).
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Skin toxicity, diarrhea, dehydration and fatigue have been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg).
    2) SEVERE TOXICITY: No severe toxicity were reported following doses of approximately twice the recommended therapeutic dose (12 mg/kg).
    0.2.20) REPRODUCTIVE
    A) Panitumumab is classified as FDA pregnancy category C. Adequate and well-controlled studies with panitumumab in pregnant women are not available. Significant increases in embryolethality and abortions were observed in animals treated with panitumumab during organogenesis. It is no known if panitumumab is excreted into human breast milk. As human IgG is secreted into human milk and panitumumab is a recombinant, human IgG2 kappa monoclonal antibody, it may also be secreted into human milk.

Laboratory Monitoring

    A) Monitor vital signs.
    B) Monitor fluid status and electrolytes in patients with signs and symptoms of dehydration, or severe vomiting or diarrhea. Replace volume and electrolytes as indicated.
    C) Monitor for clinical evidence of an infusion reaction.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. In patients with infusion reactions, permanent discontinuation of panitumumab may be required depending on the severity and/or persistence of the reaction. Oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required depending on the severity of the infusion reaction.
    C) DECONTAMINATION
    1) Decontamination is not indicated because an ingestion is unlikely; panitumumab is administered parenterally.
    D) AIRWAY MANAGEMENT
    1) Endotracheal intubation and mechanical ventilation may be required in patients with severe infusion reactions, but this is rare.
    E) ANTIDOTE
    1) None
    F) COMPLICATION OF INFUSION
    1) Discontinue infusion. Permanent discontinuation of panitumumab may be required depending on the severity and/or persistence of the reaction. Oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required depending on the severity of the infusion reaction.
    G) PATIENT DISPOSITION
    1) OBSERVATION CRITERIA: Mild to moderately symptomatic patients should be sent to a health care facility for evaluation and treated until symptoms resolve.
    2) ADMISSION CRITERIA: Patients who remain symptomatic despite adequate treatment should be admitted.
    3) CONSULT CRITERIA: Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    H) PITFALLS
    1) When managing a suspected panitumumab overdose, the treating physician should be cognizant of the possibility of multi-drug involvement.
    I) PHARMACOKINETICS
    1) At steady state, after at least 3 doses (6 mg/kg as 1-hour infusion every 2 weeks), the peak and trough concentrations were 213 mcg/mL +/- 59 and 39 +/- 14 mcg/mL, respectively; the mean total body clearance was 4.9 +/- 1.4 mL/kg/day, and the elimination half-life was approximately 7.5 days (range: 3.6 to 10.9 days).
    J) DIFFERENTIAL DIAGNOSIS
    1) Panitumumab may be administered to cancer patients in combination with other antineoplastic agents. Other drugs causing similar infusion-related reactions may include: oxaliplatin, cetuximab, and bevacizumab. Pulmonary fibrosis may occur with nitrosoureas or bleomycin.

Range Of Toxicity

    A) TOXICITY: Skin toxicity, diarrhea, dehydration and fatigue have been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg).
    B) THERAPEUTIC DOSE: ADULTS: The recommended dose of panitumumab is 6 mg/kg by an intravenous infusion over 60 minute every 14 days. Infuse doses higher than 1000 mg over 90 minutes. CHILDREN: The safety and effectiveness of panitumumab in pediatric patients have not been established.

Clinical Effects

Summary Of Exposure

    A) USES: Used for the treatment of epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
    B) PHARMACOLOGY: Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody and binds to human EGFR specifically, on both normal and tumor cells. Panitumumab competitively inhibits the binding of ligands for EGFR.
    C) EPIDEMIOLOGY: Overdoses are rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: COMMON: Dermatologic effects develop in most (90%) patients, and include: erythema (65%), acneiform dermatitis (57%), pruritus (57%), nail changes (29%), paronychia (25%), exfoliation (25%), skin fissures (20%), and dry skin (10%). Other adverse effects include: hypomagnesemia (38%), fatigue (26%), abdominal pain (25%), nausea/vomiting (23% and 19%), diarrhea (21%), constipation (21%), and cough (14%). Less common adverse effects include: hyperglycemia, hypokalemia, hypocalcemia, cheilitis, ocular toxicities (e.g. conjunctivitis, ocular hyperemia, increased lacrimation, eye/eyelid irritation, and eyelash growth), thrombophlebitis, bone pain, back pain, asthenia, dyspnea, and infectious complications. Rare, but serious complications include pulmonary fibrosis and infusion-related toxicity (e.g. anaphylactoid reactions, bronchospasm, hypotension).
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Skin toxicity, diarrhea, dehydration and fatigue have been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg).
    2) SEVERE TOXICITY: No severe toxicity were reported following doses of approximately twice the recommended therapeutic dose (12 mg/kg).

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), eye-related toxicities (all grades) occurred in 15% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 2% of patients who received BSC alone (n=234); additionally, severe eye-related toxicities (grade 3 and 4) were reported in less than 1% and 0%, respectively . In this study, the following ocular effects were also reported: eye/eyelid irritation (1%); increased lacrimation (2%); ocular hyperemia (3%); conjunctivitis (4%); growth of eyelashes (6%). The median time to development of ocular toxicities in this study was 14 days (15 days for severe toxicity) and the median time to resolution following the last panitumumab dose was 84 days (Prod Info VECTIBIX(R) IV solution, 2008).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) PERIPHERAL EDEMA
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), peripheral edema (all grades) occurred in 12% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 6% of patients who received BSC alone (n=234); additionally, severe peripheral edema (grade 3 and 4) was reported in 1% and less than 1%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Grades 2 to 4 peripheral edema occurred in 5% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), diarrhea (all grades) occurred in 21% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 11% of patients who received BSC alone (n=234); additionally, severe diarrhea (grade 3 and 4) was reported in 2% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) COMBINATION THERAPY - In a multicenter, randomized, controlled trial in patients with previously untreated metastatic colorectal cancer (n=1053), diarrhea (grade 3 and 4) occurred in 23% of patients who received panitumumab plus bevacizumab (BEV) and oxaliplatin- or irinotecan-based, 5-fluorouracil-containing chemotherapy compared to 12% of patients who received BEV and chemotherapy alone (Prod Info VECTIBIX(R) IV solution, 2008).
    c) COMBINATION THERAPY - In a single-arm study (n=19), grade 3 and 4 diarrhea occurred in 58% of patients who received panitumumab plus irinotecan, 5-fluorouracil, and leucovorin (IFL); additionally one patient experienced grade 5 diarrhea. In another single-arm study (n=24), grade 3 diarrhea occurred in 25% of patients who received panitumumab plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) therapy (Prod Info VECTIBIX(R) IV solution, 2008)
    2) WITH POISONING/EXPOSURE
    a) Diarrhea and dehydration have been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg) (Prod Info VECTIBIX(R) IV solution, 2008).
    B) NAUSEA
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), nausea (all grades) occurred in 23% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 16% of patients who received BSC alone (n=234); additionally, severe nausea (grade 3 and 4) was reported in 1% and less than 1%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) COMBINATION THERAPY - Grade 3 nausea occurred in 5% of patients (n=19) treated with panitumumab in combination with irinotecan and bolus 5-fluorouracil/leucovorin (IFL) for the first-line treatment of metastatic colorectal cancer in a phase 2 clinical trial (Hecht et al, 2006).
    C) VOMITING
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), vomiting (all grades) occurred in 19% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 12% of patients who received BSC alone (n=234); additionally, severe vomiting (grade 3 and 4) was reported in 2% and 1%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Grades 3 or 4 vomiting occurred in 2 of 148 patients who received panitumumab monotherapy for the treatment of metastatic colorectal cancer (Malik et al, 2005).
    D) CHEILITIS
    1) WITH THERAPEUTIC USE
    a) Cheilitis occurred in 7% of patients (n=91) who received panitumumab monotherapy for the treatment of metastatic colorectal cancer in one phase 2 clinical trial (Berlin et al, 2006) and in 2% of patients (n=88) in another phase 2 clinical trial (Hecht et al, 2006a).
    E) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), abdominal pain (all grades) occurred in 25% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 17% of patients who received BSC alone (n=234); additionally, severe abdominal pain (grade 3 and 4) was reported in 7% and 5%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Grades 2 to 4 abdominal pain occurred in 6% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).
    F) LOSS OF APPETITE
    1) WITH THERAPEUTIC USE
    a) Anorexia occurred in 2 (grade 1, n=1; grade 2, n=1) of 23 patients treated with panitumumab as monotherapy for metastatic colorectal cancer in a phase 2 clinical trial (Meropol et al, 2003).
    b) Grades 2 to 4 anorexia occurred in 5% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial. Anorexia was not dose-related (Rowinsky et al, 2004).
    G) STOMATITIS
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), stomatitis (all grades) occurred in 7% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 1% of patients who received BSC alone (n=234) (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Stomatitis occurred in 6 (grade 1, n=5; grade 2, n=1) of 23 patients treated with panitumumab as monotherapy for metastatic colorectal cancer in a phase 2 clinical trial (Meropol et al, 2003).
    H) CONSTIPATION
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), constipation (all grades) occurred in 21% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 9% of patients who received BSC alone (n=234); additionally, severe constipation (grade 3 and 4) was reported in 3% and 1%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Grades 2 to 4 constipation occurred in 6% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).
    I) INFLAMMATORY DISEASE OF MUCOUS MEMBRANE
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), mucosal inflammation (all grades) occurred in 6% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 1% of patients who received BSC alone (n=234); additionally, severe mucosal inflammation (grade 3 and 4) was reported in less than 1% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) THROMBOPHLEBITIS
    1) WITH THERAPEUTIC USE
    a) Grades 2 to 4 thrombophlebitis occurred in 5% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATOLOGIC TOXICITY
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), all skin/integument toxicity (all grades) occurred in 90% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 6% of patients who received BSC alone (n=234); grade 3 and 4 all skin/integument toxicity occurred in 16% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) COMBINATION THERAPY - In a multicenter, randomized, controlled trial in patients with previously untreated metastatic colorectal cancer (n=1053), rash/dermatitis/acneiform (grade 3 and 4) occurred in 26% of patients who received panitumumab plus bevacizumab (BEV) and oxaliplatin- or irinotecan-based, 5-fluorouracil-containing chemotherapy compared to 1% of patients who received BEV and chemotherapy alone(Prod Info VECTIBIX(R) IV solution, 2008).
    2) WITH POISONING/EXPOSURE
    a) Skin toxicity has been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg) (Prod Info VECTIBIX(R) IV solution, 2008).
    B) ACNE
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), acne (all grades) occurred in 13% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 0% of patients who received BSC alone (n=234); additionally, severe acne (grade 3 and 4) was reported in 1% of panitumumab-treated patients (Prod Info VECTIBIX(R) IV solution, 2008).
    C) ERUPTION
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), rash (all grades) occurred in 22% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 1% of patients who received BSC alone (n=234); additionally, severe rash (grade 3 and 4) was reported in 1% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) All patients (n=23) treated with panitumumab as monotherapy for metastatic colorectal cancer in a phase 2 clinical trial had skin rash, with 14 grade 1, 7 grade 2, and 2 grade 3 rashes (Meropol et al, 2003).
    c) Grade 3 or 4 rash occurred in 5 of 148 patients who received panitumumab monotherapy for the treatment of metastatic colorectal cancer (Malik et al, 2005).
    d) Skin rash was the most common toxicity in a phase 2 clinical trial of patients treated with panitumumab for metastatic renal cell carcinoma. Skin rash typically occurred in a periorificial distribution in the face and also in the upper trunk. It typically resembled an acneiform-type drug reaction but also had maculopapular characteristics in some patients. The skin rash typically occurred by the second or third week of treatment, reached its peak by 3 to 5 weeks, and gradually decreased despite continued treatment with panitumumab. Minimal or no accompanying symptoms occurred. The incidence of cutaneous toxicity was 68%, 95%, 87%, and 100% at doses of 1 milligram/kilogram (mg/kg; n=22), 1.5 mg/kg (n=22), 2 mg/kg (n=23), and 2.5 mg/kg (n=21), respectively (Rowinsky et al, 2004).
    e) In a phase 1 study, all patients (n=43) experienced transient acneiform rashes in a dose-dependent manner (Figlin et al, 2002).
    f) COMBINATION THERAPY - In a multicenter, randomized, controlled trial in patients with previously untreated metastatic colorectal cancer (n=1053), rash/dermatitis/acneiform (grade 3 and 4) occurred in 26% of patients who received panitumumab plus bevacizumab (BEV) and oxaliplatin- or irinotecan-based, 5-fluorouracil-containing chemotherapy compared to 1% of patients who received BEV and chemotherapy alone (Prod Info VECTIBIX(R) IV solution, 2008).
    D) ITCHING OF SKIN
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), pruritus (all grades) occurred in 57% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 2% of patients who received BSC alone (n=234); additionally, severe pruritus (grade 3 and 4) was reported in 2% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Grades 3 or 4 pruritus occurred in 1 of 148 patients who received panitumumab monotherapy for the treatment of metastatic colorectal cancer (Malik et al, 2005).
    E) GENERALIZED EXFOLIATIVE DERMATITIS
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), skin exfoliation (all grades) occurred in 25% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 0% of patients who received BSC alone (n=234); additionally, severe skin exfoliation (grade 3 and 4) was reported in 2% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    F) PARONYCHIA
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), paronychia (all grades) occurred in 25% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 0% of patients who received BSC alone (n=234); additionally, severe paronychia (grade 3 and 4) was reported in 2% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    G) FISSURE IN SKIN
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), skin fissures (all grades) occurred in 20% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to less than 1% of patients who received BSC alone (n=234); additionally, severe skin fissures (grade 3 and 4) were reported in 1% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    H) DRY SKIN
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), dry skin (all grades) occurred in 10% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 0% of patients who received BSC alone (n=234) (Prod Info VECTIBIX(R) IV solution, 2008).
    I) ACNEIFORM ERUPTION
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), acneiform dermatitis (all grades) occurred in 57% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 1% of patients who received BSC alone (n=234); additionally, severe acneiform dermatitis (grade 3 and 4) was reported in 7% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) COMBINATION THERAPY - In a multicenter, randomized, controlled trial in patients with previously untreated metastatic colorectal cancer (n=1053), rash/dermatitis/acneiform (grade 3 and 4) occurred in 26% of patients who received panitumumab plus bevacizumab (BEV) and oxaliplatin- or irinotecan-based, 5-fluorouracil-containing chemotherapy compared to 1% of patients who received BEV and chemotherapy alone (Prod Info VECTIBIX(R) IV solution, 2008).
    J) ERYTHEMA
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), erythema (all grades) occurred in 65% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 1% of patients who received BSC alone (n=234); additionally, severe erythema (grade 3 and 4) was reported in 5% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    K) NAIL CHANGES
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), nail toxicity (all grades) occurred in 29% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 0% of patients who received BSC alone (n=234); additionally, severe nail toxicity (grade 3 and 4) was reported in 2% and 0%, respectively. Other nail disorders (all grades) occurred in 9% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 0% of patients who received BSC alone (n=234) (Prod Info VECTIBIX(R) IV solution, 2008).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) BACKACHE
    1) WITH THERAPEUTIC USE
    a) Grades 2 to 4 back pain occurred in 13% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).
    B) BONE PAIN
    1) WITH THERAPEUTIC USE
    a) Grades 2 to 4 bone pain occurred in 5% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPERGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) Grades 2 to 4 hyperglycemia occurred in 5% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) A grade 3 hypersensitivity reaction occurred in 1 of 91 patients who received panitumumab monotherapy for the treatment of metastatic colorectal cancer. The event resolved with appropriate treatment and the patient went on to receive further doses of panitumumab with premedication for hypersensitivity (Berlin et al, 2006). .

Reproductive

    3.20.1) SUMMARY
    A) Panitumumab is classified as FDA pregnancy category C. Adequate and well-controlled studies with panitumumab in pregnant women are not available. Significant increases in embryolethality and abortions were observed in animals treated with panitumumab during organogenesis. It is no known if panitumumab is excreted into human breast milk. As human IgG is secreted into human milk and panitumumab is a recombinant, human IgG2 kappa monoclonal antibody, it may also be secreted into human milk.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Pregnant cynomolgus monkeys administered panitumumab during organogenesis (gestation days 20 to 50) at doses approximately 1.25 to 5-fold greater than the recommended human dose resulted in significant embryolethal and abortifacient effects. No teratogenic effects or fetal malformations were noted in the offspring, but anti-panitumumab titers were present in some of the offspring (n=14/27) (Prod Info Vectibix(R) intravenous injection, 2014).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The manufacturer has classified panitumumab as FDA pregnancy category C (Prod Info Vectibix(R) intravenous injection, 2014).
    2) There are no adequate and well-controlled studies with panitumumab in pregnant women. The effects, if any, on the developing fetus are unknown. Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody. As human IgG is known to cross the placental barrier, panitumumab may also be passed on from mother to the fetus. Panitumumab also binds to human epidermal growth factor receptors (EGFR), and in animal studies EGFR has been implicated in the control of prenatal development, as well as normal organogenesis, proliferation, and differentiation of the developing embryo. Due to the lack of human safety information, panitumumab should be used in pregnant women only if the potential benefit outweighs the potential risk to the fetus (Prod Info Vectibix(R) intravenous injection, 2014).
    3) Women of childbearing potential must use appropriate contraceptive measures during panitumumab treatment and for 6 months after the last panitumumab dose. If panitumumab is used during pregnancy or if a woman becomes pregnant while on panitumumab, she should be informed of the potential risk for loss of pregnancy or potential hazard to the fetus. Women exposed to panitumumab during pregnancy are encouraged to participate in Amgen's Pregnancy Surveillance Program, which can be accessed by calling 1-800-772-6436 (Prod Info Vectibix(R) intravenous injection, 2014).
    B) ANIMAL STUDIES
    1) Embryolethal and abortifacient effects were evident in pregnant cynomolgus monkeys who were treated with panitumumab during organogenesis (gestation days 20 to 50) at doses approximately 1.25 to 5-fold greater than the recommended human dose (Prod Info Vectibix(R) intravenous injection, 2014).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is no known if panitumumab is excreted into human breast milk. As human IgG is secreted into human milk and panitumumab is a recombinant, human IgG2 kappa monoclonal antibody, it may also be secreted into human milk. Since the potential for absorption and harm to the infant is unknown, it is recommended that women discontinue nursing during treatment with panitumumab and for 2 months after the last dose of panitumumab. Women exposed to panitumumab during nursing are encouraged to participate in Amgen's Lactation Surveillance Program, which can be accessed by calling 1-800-772-6436 (Prod Info Vectibix(R) intravenous injection, 2014).
    3.20.5) FERTILITY
    A) LACK OF INFORMATION
    1) It is unknown whether panitumumab can impair fertility in humans (Prod Info Vectibix(R) intravenous injection, 2014).
    B) ANIMAL STUDIES
    1) Normally cycling, female cynomolgus monkeys treated weekly with 1.25 to 5 times the recommended human dose of panitumumab (based on body weight) experienced prolonged menstrual cycles and/or amenorrhea. Menstrual cycle irregularities were accompanied by both a decrease and delay in peak progesterone and 17 beta-estradiol levels. Following the discontinuation of panitumumab, normal menstrual cycling returned in most animals (Prod Info Vectibix(R) intravenous injection, 2014).
    2) There were no adverse effects in reproductive organs of male cynomolgus monkeys treated for 26 weeks with panitumumab at doses of up to approximately 5-fold the recommended human dose (based on body weight) (Prod Info Vectibix(R) intravenous injection, 2014).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS339177-26-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PULMONARY EMBOLISM
    1) WITH THERAPEUTIC USE
    a) COMBINATION THERAPY - In a multicenter, randomized, controlled trial in patients with previously untreated metastatic colorectal cancer (n=1053), pulmonary embolism (grade 3 to 5) occurred in 7% of patients who received panitumumab plus bevacizumab (BEV) and oxaliplatin- or irinotecan-based, 5-fluorouracil-containing chemotherapy compared to 4% of patients who received BEV and chemotherapy alone. Additionally, fatal events were reported in three (less than 1%) panitumumab-treated patients (Prod Info VECTIBIX(R) IV solution, 2008).
    B) FIBROSIS OF LUNG
    1) WITH THERAPEUTIC USE
    a) In clinical trials, pulmonary fibrosis occurred in less than 1% of patients (n=2 of 1467) treated with panitumumab (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Case reports of pulmonary fibrosis have been described with panitumumab use. Two deaths occurred in patients receiving panitumumab in combination with chemotherapy; one patient with underlying idiopathic pulmonary fibrosis died following 4 panitumumab doses and a second patient with bilateral pulmonary infiltrates and hypoxia died after 23 panitumumab doses. Another patient developed cough and wheezing 8 days after the first dose of single-agent panitumumab, exertional dyspnea after 7 doses, and persistent symptoms and CT evidence of pulmonary fibrosis after 11 doses (Prod Info VECTIBIX(R) IV solution, 2008).
    C) COUGH
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), cough (all grades) occurred in 14% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 7% of patients who received BSC alone (n=234); additionally, severe cough (grade 3 and 4) was reported in less than 1% and 0%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Grades 2 to 4 cough occurred in 9% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial (Rowinsky et al, 2004).
    D) DYSPNEA
    1) WITH THERAPEUTIC USE
    a) Grades 2 to 4 dyspnea occurred in 10% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial. One patient experienced severe dyspnea (Rowinsky et al, 2004).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) FATIGUE
    1) WITH THERAPEUTIC USE
    a) In a multinational, randomized, controlled trial in patients with metastatic colorectal cancer who had progressed on or following a regimen with a fluoropyrimidine, oxaliplatin, and irinotecan (n=463), fatigue (all grades) occurred in 26% of patients who received panitumumab plus best supportive care (BSC) (n=229) compared to 15% of patients who received BSC alone (n=234); additionally, severe fatigue (grade 3 and 4) was reported in 4% and 3%, respectively (Prod Info VECTIBIX(R) IV solution, 2008).
    b) Grades 3 or 4 fatigue occurred in 4 of 148 patients who received panitumumab monotherapy for the treatment of metastatic colorectal cancer (Malik et al, 2005).
    c) COMBINATION THERAPY - Grade 3 fatigue occurred in 11% of patients (n=19) treated with panitumumab in combination with irinotecan and bolus 5-fluorouracil/leucovorin (IFL) for the first-line treatment of metastatic colorectal cancer in a phase 2 clinical trial (Hecht et al, 2006).
    2) WITH POISONING/EXPOSURE
    a) Fatigue has been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg) (Prod Info VECTIBIX(R) IV solution, 2008).
    B) ASTHENIA
    1) WITH THERAPEUTIC USE
    a) Asthenia occurred in 8 (grade 1, n=5; grade 2, n=2; grade 3, n=1) of 23 patients treated with panitumumab as monotherapy for metastatic colorectal cancer in a phase 2 clinical trial (Meropol et al, 2003).
    b) Grades 2 to 4 asthenia occurred in 15% of patients (n=88) who received panitumumab monotherapy for metastatic renal cell carcinoma in a phase 2 clinical trial. Asthenia was not dose-related (Rowinsky et al, 2004).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs.
    B) Monitor fluid status and electrolytes in patients with signs and symptoms of dehydration, or severe vomiting or diarrhea. Replace volume and electrolytes as indicated.
    C) Monitor for clinical evidence of an infusion reaction.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients who remain symptomatic despite adequate treatment should be admitted.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Mild to moderately symptomatic patients should be sent to health care facility for evaluation and treated until symptoms resolve.

Monitoring

    A) Monitor vital signs.
    B) Monitor fluid status and electrolytes in patients with signs and symptoms of dehydration, or severe vomiting or diarrhea. Replace volume and electrolytes as indicated.
    C) Monitor for clinical evidence of an infusion reaction.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not indicated because an ingestion is unlikely; panitumumab is administered parenterally.

Range Of Toxicity

Summary

    A) TOXICITY: Skin toxicity, diarrhea, dehydration and fatigue have been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg).
    B) THERAPEUTIC DOSE: ADULTS: The recommended dose of panitumumab is 6 mg/kg by an intravenous infusion over 60 minute every 14 days. Infuse doses higher than 1000 mg over 90 minutes. CHILDREN: The safety and effectiveness of panitumumab in pediatric patients have not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) The recommended dose of panitumumab is 6 mg/kg IV infused over 60 minutes every 14 days. Infuse doses higher than 1000 mg over 90 minutes; if the first dose is tolerated, administer subsequent infusions over 30 to 60 minutes (Prod Info Vectibix(R) intravenous injection, 2014).
    7.2.2) PEDIATRIC
    A) The safety and effectiveness of panitumumab in pediatric patients have not been established (Prod Info Vectibix(R) intravenous injection, 2014).

Maximum Tolerated Exposure

    A) Skin toxicity, diarrhea, dehydration and fatigue have been reported in patients receiving doses up to approximately twice the recommended therapeutic dose (12 mg/kg) (Prod Info VECTIBIX(R) IV solution, 2008).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) The mean area under the curve, following multiple doses given at 6 mg/kg as a 1-hour infusion every 2 weeks, was 1306 +/- 374 mcg x day/mL (Prod Info VECTIBIX(R) IV solution, 2008).

Workplace Standards

    A) ACGIH TLV Values for CAS339177-26-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS339177-26-3 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS339177-26-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS339177-26-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody and binds to human epidermal growth factor receptors (EGFR) specifically, on both normal and tumor cells. Panitumumab competitively inhibits the binding of ligands for EGFR. This activity prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, which then results in inhibition of cell growth, apoptosis induction, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR (Prod Info VECTIBIX(R) IV solution, 2008).

Physicochemical

Physical Characteristics

    A) Sterile and colorless liquid that may contain a small amount of translucent-to-white, proteinaceous, amorphous particulates of panitumumab (Prod Info VECTIBIX(R) injection for intravenous infusion, 2010).

Ph

    A) 5.6 to 6 (Prod Info VECTIBIX(R) injection for intravenous infusion, 2010)

Molecular Weight

    A) Approximately 147 kiloDaltons (Prod Info VECTIBIX(R) injection for intravenous infusion, 2010)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    5) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    6) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    11) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    12) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    13) American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.
    14) Berlin J, Neubauer M, Swanson P, et al: Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing at least 10% epidermal growth factor receptor (EGFr).. Proc Am Soc Clin Oncol 2006; 24(18S):[3548]-.
    15) DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.
    16) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    17) Figlin RA, Belldegrun AS, Crawford J, et al: ABX-EGF, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with advanced cancer: phase 1 clinical results. Proc Am Soc Clin Oncol 2002; 21:[35]-.
    18) Hecht J, Mitchell E, Baranda J, et al: Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing low (1-9%) or negative (less than 1%) levels of epidermal growth factor receptor (EGFr). Proc Am Soc Clin Oncol 2006a; 24(18S):[3547]-.
    19) Hecht J, Posey J, Tchekmedyian S, et al: Panitumumab in combination with 5-fluorouracil, leucovorin, and irinotecan (IFL) or FOLFIRI for first-line treatment of metastatic colorectal cancer (mCRC).. Proc Am Soc Clin Oncol 2006; 2006:[237]-.
    20) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.
    21) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.
    22) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.
    23) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.
    24) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.
    25) IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.
    26) International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.
    27) International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.
    28) Lieberman P, Nicklas R, Randolph C, et al: Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol 2015; 115(5):341-384.
    29) Lieberman P, Nicklas RA, Oppenheimer J, et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126(3):477-480.
    30) Malik I, Hecht JR, Patnaik A, et al: Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Proc Am Soc Clin Oncol 2005; 23(16S):[3520]-.
    31) Meropol NJ, Berlin J, Hecht JR, et al: Multicenter study of ABX-EGF monotherapy in patients with metastatic colorectal cancer.. Proc Am Soc Clin Oncol 2003; 22:[1026]-.
    32) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    33) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.
    34) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.
    35) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.
    36) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.
    37) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    38) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    39) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    40) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    41) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    42) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    43) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    44) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    45) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    46) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    47) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    48) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    49) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    50) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    51) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    52) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    53) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    54) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    55) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    56) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    57) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    58) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    59) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    60) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    61) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    62) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    63) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    64) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    65) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    66) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    67) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    68) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    69) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    70) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    71) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    72) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    73) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    74) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    75) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    76) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    77) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    78) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    79) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    80) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    81) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    82) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    83) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    84) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    85) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    86) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    87) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    88) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    89) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    90) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    91) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    92) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    93) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    94) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    95) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    96) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    97) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    98) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    99) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    100) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    101) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    102) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    103) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    104) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    105) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.
    106) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    107) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    108) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    109) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    110) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    111) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    112) National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.
    113) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    114) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    115) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    116) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    117) Nowak RM & Macias CG : Anaphylaxis on the other front line: perspectives from the emergency department. Am J Med 2014; 127(1 Suppl):S34-S44.
    118) Product Information: VECTIBIX(R) IV solution, panitumumab IV solution. Amgen Inc, Thousand Oaks, CA, 2008.
    119) Product Information: VECTIBIX(R) injection for intravenous infusion, panitumumab injection for intravenous infusion. Amgen, Thousand Oaks, CA, 2010.
    120) Product Information: Vectibix(R) intravenous injection, panitumumab intravenous injection. Amgen, Inc. (per manufacturer), Thousand Oaks, CA, 2014.
    121) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    122) Rowinsky EK, Schwartz GH, Gollob JA, et al: Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol 2004; 22(15):3003-3015.
    123) U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.
    124) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.
    125) U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.
    126) U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.
    127) U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    128) U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    129) U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.
    130) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    131) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    132) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    133) Vanden Hoek,TL; Morrison LJ; Shuster M et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.