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Panitumumab

Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: Disulfide with human monoclonal ABX-EGF light chain anti-(human epidermal growth factor receptor) (human monoclonal ABX-EGF heavy chain) immunoglobulin dimer
Molecular Formula: C6306H9732N1672O1994S46
CAS Number: 339177-26-3
Brands: Vectibix

Warning(s)

  • Dermatologic Toxicity
  • Dermatologic toxicities were reported in 89% of patients and were severe in 12% of patients receiving panitumumab monotherapy in controlled trials.1 13 24 (See Dermatologic Toxicity under Dosage and Administration and Dermatologic, Mucosal, and Ocular Toxicity under Cautions.)

  • Infusion-related Reactions
  • Severe infusion-related reactions reported in about 1% of patients.1 14

  • Fatal infusion reactions not reported with panitumumab, but have occurred with other monoclonal antibody preparations.1 (See Infusion-related Reactions under Dosage and Administration and under Cautions.)

Introduction

Antineoplastic agent; a recombinant human IgG2 kappa monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR; also called an epidermal growth factor receptor [EGFR] inhibitor).1 2 3 4 5 6 7 8 9 13 14 22 31 35 37 42

Uses for Panitumumab

Colorectal Cancer

Used as a single agent for the treatment of metastatic colorectal cancer that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens in adult patients with tumors that express EGFR.1 2 3 4 5 7 8 9 11 13 14 21 22 31 32 37

Slideshow: 2014 Update: First Time Brand-to-Generic Switches

Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for panitumumab in patients whose tumors had KRAS (also called K-ras) mutations in codon 12 or 13;1 33 44 ASCO44 and some clinicians26 29 30 31 32 33 recommend that all patients with metastatic colorectal cancer who are potential candidates for EGFR inhibitor therapy (e.g., panitumumab, cetuximab) have their tumor tested for KRAS mutations26 29 30 31 32 33 44 in a Clinical Laboratory Improvement Amendments (CLIA)-accredited laboratory.44 If KRAS mutation in codon 12 or 13 is detected, use of panitumumab is not recommended.1 44

Efficacy of panitumumab monotherapy determined based on progression-free survival; actual clinical benefits (e.g., improvement in disease-related symptoms, increased survival) not adequately studied.1 13 37

Available data do not support the use of panitumumab after clinical failure of cetuximab in metastatic colorectal cancer and some authorities do not recommend the use of either of these agents after clinical failure of the other.11 However, panitumumab potentially may be used as an alternative to cetuximab therapy (e.g., if cetuximab is contraindicated or not tolerated).11 19 20

Panitumumab is not approved for use in combination with chemotherapy for the treatment of metastatic colorectal cancer.1 (See Use in Combination with other Chemotherapeutic Regimens under Cautions and Specific Drugs or Therapies under Interactions.)

Panitumumab Dosage and Administration

General

  • Premedication to minimize the risk of infusion-related reactions does not appear to be necessary; however, appropriate medical resources for the treatment of severe reactions should be available during panitumumab infusions.1 7 8 9 15 19 22

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 Do not administer by rapid IV injection (e.g., IV push or “bolus”).1

Solution should be colorless and may contain a small amount of visible, translucent-to-white, amorphous, proteinaceous particulates of panitumumab; do not administer if discoloration observed.1

Do not shake vials.1

Use infusion pump to administer.1 Prior to and following administration, flush line with 0.9% sodium chloride injection.1 Administer drug through a low-protein-binding 0.2- or 0.22-mcm inline filter.1

Dilution

Withdraw appropriate dose of panitumumab injection solution (containing 20 mg/mL) and dilute in 0.9% sodium chloride injection to a total volume of 100 mL; doses >1 g should be diluted in 0.9% sodium chloride injection to a total volume of 150 mL.1 Final concentration should not exceed 10 mg of panitumumab per mL.1

Mix diluted solution by gentle inversion; do not shake.1

Do not mix or dilute panitumumab with other drugs or infusion solutions.1

Rate of Administration

Administer over 60 minutes if dose is ≤1 g; administer over 90 minutes if dose is >1 g.1

Dosage

Adults

Colorectal Cancer
IV

For the management of previously treated, EGFR-expressing metastatic colorectal cancer as monotherapy, 6 mg/kg over 60 minutes every 14 days.1 2 4 9 13 Doses >1 g should be infused over 90 minutes.1 2 9 In the randomized controlled trial evaluating panitumumab monotherapy for metastatic colorectal cancer, a median of 5 doses was administered.1

Dosage Modification for Toxicity

Infusion-related Reactions

If mild or moderate (grade 1 or 2) infusion-related reactions occur, reduce infusion rate by 50% for the duration of that infusion.1 9

If severe (grade 3 or 4) infusion-related reactions occur, discontinue therapy immediately and permanently.1 9 15

Dermatologic Toxicity

If severe (grade 3 or 4) or intolerable dermatologic toxicity occurs, withhold therapy.1 If toxicity does not improve to ≤ grade 2 within 1 month, permanently discontinue therapy.1

If dermatologic toxicity improves to ≤ grade 2 and patient is symptomatically improved after withholding no more than 2 doses, resume treatment at 50% of the original dosage.1 Dosage may then be increased in increments of 25% of the original dosage up to the recommended dosage of 6 mg/kg if toxicity does not recur.1 If toxicity recurs, permanently discontinue therapy.1

Special Populations

No special population dosage recommendations at this time.1

Cautions for Panitumumab

Contraindications

  • None known.1

Warnings/Precautions

Warnings

Dermatologic, Mucosal, and Ocular Toxicity

Dermatologic toxicity, which may affect the skin, mucosa, eyes, and/or nails, was reported in approximately 90% of patients and was severe (grade 3 or 4) in 16% of patients in a large, controlled trial.1 3 9 12 13 14 16 43 Manifested as dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and/or skin fissures.1 12 13 14 43 Severe dermatologic toxicity may result in infectious complications, including sepsis, septic death, and abscesses requiring incision and drainage.1 12

Mucosal toxicity, including oral mucositis and stomatitis, reported in 6–7% of patients receiving panitumumab therapy; one case of grade 3 mucosal inflammation reported.1

Ocular toxicity, including conjunctivitis, ocular hyperemia, increased lacrimation, and eye/eyelid irritation, reported in 15% of patients.1 9 14

Paronychia reported in 25% of patients receiving panitumumab, with severe cases (grade 3 or 4) reported in 2%; other nail disorders reported in 9% of patients.1 12 13

Median time to development of dermatologic and ocular toxicity was 14 days and median time to most severe toxicity was 15 days after the first dose of panitumumab; median time to resolution after the last dose of panitumumab was 84 days.1

Withhold panitumumab for severe or life-threatening dermatologic toxicity.1 If severe adverse dermatologic effects occur, monitor patients for possible inflammatory or infectious complications and initiate appropriate therapy.1 12 14 Prevention and treatment should be carefully individualized and may require specialized care; topical and/or systemic antibiotics, topical emollients, topical corticosteroids, and/or systemic antihistamines may be helpful in some cases.7 12 14 41 43 Dosage modifications, including possible discontinuance of therapy, may be required.1 12 14 (See Dermatologic Toxicity in Boxed Warning and under Dosage and Administration.)

Infusion-related Reactions

Infusion-related reactions occurred in 4% and severe reactions (grade 3 or 4) occurred in 1% of patients receiving panitumumab in the monotherapy clinical trial (designated Study 1 by the manufacturer).1 14 In all clinical studies, severe infusion reactions occurred in approximately 1% of the panitumumab-treated patients.1 Serious infusion reactions included anaphylactic reactions, bronchospasm, and hypotension.1 No fatalities were reported; however, fatalities have occurred with other monoclonal antibody products.1 A reduction in infusion rate or discontinuance of therapy may be necessary depending on severity of the reaction.1 (See Infusion-related Reactions in Boxed Warning and under Dosage and Administration.)

Pulmonary Effects

Pulmonary fibrosis (including 2 fatalities; 1 case occurred in a patient with preexisting idiopathic pulmonary fibrosis) reported in <1% of patients receiving panitumumab.1 Use with caution in patients with preexisting lung disease; such patients were excluded from clinical trials.1 24 Permanently discontinue panitumumab in patients who develop interstitial lung disease, pneumonitis, or lung infiltrates during therapy.1

Other Warnings and Precautions

Use in Combination with other Chemotherapeutic Regimens

Panitumumab is not indicated for use in combination with chemotherapy.1

In a large, randomized, open-label, multicenter trial, addition of panitumumab to a bevacizumab plus chemotherapy regimen (containing either oxaliplatin or irinotecan and fluorouracil) in the first-line treatment of metastatic colorectal cancer resulted in poorer outcomes (i.e., decreased overall survival) and increased toxicity (e.g., higher incidence of grade 3–5 adverse reactions).1 18 27 39 Grade 3/4 adverse reactions occurred more frequently in panitumumab-treated patients compared with those in non-panitumumab-containing treatment arms and included dermatologic toxicity (e.g., rash, acneiform dermatitis), diarrhea, dehydration (mainly in patients with diarrhea), hypokalemia, stomatitis or mucositis, and hypomagnesemia.1 18 27 39 Grade 3–5 pulmonary embolism also occurred more frequently in panitumumab-treated patients compared with non-panitumumab-containing treatment arms (7% and 4%, respectively).1 18 27 39 Because of the toxicities experienced, patients randomized to panitumumab, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each agent (oxaliplatin, irinotecan, bolus fluorouracil, and/or infusional fluorouracil) over the first 24 weeks compared with those receiving bevacizumab plus chemotherapy.1

In another clinical study, addition of panitumumab to the irinotecan, direct IV injection (“bolus”) fluorouracil, and leucovorin (IFL) regimen resulted in an increased incidence and severity of chemotherapy-induced diarrhea (58% incidence of grade 3/4 diarrhea; one fatal case of grade 5 diarrhea).1 17 Grade 3 diarrhea reported in 25% of patients receiving panitumumab plus irinotecan, continuous fluorouracil infusion, and leucovorin (FOLFIRI).1 17

Severe diarrhea and dehydration, which may lead to acute renal failure and other complications, observed in patients receiving panitumumab in combination with chemotherapy.1 16 17 (See Specific Drugs or Therapies under Interactions.)

Pulmonary Effects

Pulmonary fibrosis (including 2 fatalities; 1 case occurred in a patient with preexisting idiopathic pulmonary fibrosis) reported in <1% of patients receiving panitumumab.1 Use with caution in patients with preexisting lung disease; such patients were excluded from clinical trials.1 24 Permanently discontinue panitumumab in patients who develop interstitial lung disease, pneumonitis, or lung infiltrates during therapy.1

Electrolyte Effects

Electrolyte abnormalities, including decreased serum magnesium concentrations, reported.1 9 13 14 22 Grade 3 or 4 hypomagnesemia requiring oral or IV electrolyte repletion occurred in 2% of patients in one study.1 13 In some patients, both hypomagnesemia and hypocalcemia occurred.1 Hypomagnesemia usually occurred ≥6 weeks following initiation of panitumumab therapy.1

Monitor serum electrolytes (including magnesium and calcium) periodically during and for 8 weeks following completion of panitumumab therapy.1 22

Institute appropriate treatment (e.g., oral or IV electrolyte repletion) if necessary.1 13

Photosensitivity

Exposure to sunlight can exacerbate dermatologic toxicity; the manufacturer recommends that patients apply sunscreen, wear hats, and limit sun exposure during therapy and for 2 months following the last dose of the drug.1 7 12 16

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryolethality and abortifacient effects demonstrated in animals.1 16 No studies to date in pregnant women.1 Avoid pregnancy during panitumumab therapy and for 6 months after the last dose.1 16 If used during pregnancy or patient becomes pregnant while receiving the drug, apprise of potential fetal hazard and/or risk for loss of the pregnancy.1 (See Advice to Patients.)

EGFR Testing

The manufacturer states that pretreatment assessment for EGFR expression is necessary for selecting appropriate patients for panitumumab therapy.1 23 24 However, panitumumab has demonstrated antitumor activity in patients with low or negative EGFR levels.4 24 25 Some authorities state that routine EGFR expression testing is not recommended and that patients should not be included or excluded from panitumumab therapy based solely on EGFR test results.11

If testing is conducted, EGFR expression should be assessed by laboratories with demonstrated proficiency in the specific technology being utilized.1 Improper assay performance may lead to unreliable results.1

Immunologic Effects

Appears to have relatively low immunogenic potential.1 13 Anti-panitumumab antibodies detected in ≤4.6% of panitumumab-treated patients using the acid dissociation ELISA and Biacore screening immunoassays.1 In patients whose sera tested positive in screening bioassays, neutralizing antibodies detected in ≤1.6% of samples using an in vitro biological assay.1 No known relationship between appearance of antibodies and the pharmacokinetic or tolerability profile of panitumumab.1

Specific Populations

Pregnancy

Category C.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Amgen's Pregnancy Surveillance Program: 800-772-6436.1

Lactation

IgG distributed into human milk; published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts.1 Discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.1 If nursing is interrupted, based on the mean half-life of panitumumab, nursing should not be resumed earlier than 2 months following the last dose of panitumumab.1 16

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1 16 24

Geriatric Use

In the randomized, controlled study, 42% of the patients with metastatic colorectal cancer who received panitumumab were ≥65 years of age.1 Although the clinical study of panitumumab did not include a sufficient number of geriatric patients to determine whether they respond differently than younger patients, no apparent differences in safety and efficacy relative to younger adults were reported.1 13

Common Adverse Effects

Monotherapy or combination therapy in patients with colorectal cancer: Dermatological effects (e.g., erythema, acne or acneiform dermatitis, pruritus, skin exfoliation, rash, skin fissures, dry skin),1 3 9 12 13 14 16 43 hypomagnesemia,1 9 13 14 22 paronychia and other nail disorders,1 9 12 13 14 fatigue,1 9 13 14 16 GI effects (e.g., abdominal pain, nausea, constipation, diarrhea),1 9 13 14 16 stomatitis or oral mucositis,1 dehydration,1 9 peripheral edema,1 13 14 cough,1 13 14 and ocular toxicity (e.g., conjunctivitis, increased lacrimation, ocular hyperemia, eye/eyelid irritation).1 9 14

Interactions for Panitumumab

No formal drug interaction studies have been performed.1 16

Specific Drugs or Therapies

Drug or Therapy

Interaction

Comments

Bevacizumab

Potential increased toxicity (pulmonary embolism, dermatologic toxicity, diarrhea, dehydration, hypomagnesemia) during concurrent therapy1

Manufacturer states that use of panitumumab in combination chemotherapy regimens is not approved1

Fluoropyrimidines (e.g., fluorouracil)

Pharmacokinetic interaction unlikely8

Manufacturer states that use of panitumumab in combination chemotherapy regimens is not approved1

Irinotecan

Pharmacokinetic interaction unlikely8

Potential increased incidence and severity of diarrhea1 16 17

Manufacturer states that use of panitumumab in combination chemotherapy regimens is not approved1

Paclitaxel

Pharmacokinetic interaction unlikely8

Manufacturer states that use of panitumumab in combination chemotherapy regimens is not approved1

Radiation therapy

Possible increased risk of adverse dermatologic effects; high-grade radiation dermatitis, rash, and mucositis reported in some patients receiving combined cetuximab (another EGFR inhibitor) and radiation therapy42

Panitumumab Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics are nonlinear following single-dose administration, with AUC increasing in a greater than dose-proportional manner and clearance decreasing with increasing doses; however, at doses >2 mg/kg, AUC increases in an approximately dose-proportional manner.8 1

Plasma Concentrations

Peak and trough plasma concentrations at steady-state (reached by 3rd infusion after 4 weeks) approximately 213 and 39 mcg/mL, respectively.1

Distribution

Extent

Human IgG crosses the placenta and is distributed into milk.1 Potential exists for panitumumab to cross the placenta.1 Although not known, panitumumab possibly distributed into milk.1

Elimination

Metabolism

Metabolism not fully understood.24

Elimination Route

Systemic clearance believed to be through internalization of panitumumab-EGFR complex and via the reticuloendothelial system.2 8 9 24

Half-life

Approximately 7.5 days (range: 3.6–10.9 days) following multiple dosing.1 8

Stability

Storage

Parenteral

Injection

2–8°C.1 Protect from direct sunlight; do not freeze.1 Discard any unused portion.1

Diluted infusion solutions are stable for up to 6 hours if stored at room temperature or for up to 24 hours if stored at 2–8°C.1 Do not freeze.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium chloride 0.9%1

Actions

  • Antineoplastic agent; a recombinant human IgG2 kappa monoclonal antibody that binds to human EGFR.1 2 3 4 5 6 7 8 9 13 14 22 An immunoglobulin containing a fully human framework.1 2 3 5 6 7 8

  • Panitumumab binds specifically to EGFR (HER1, c-erbB-1) on both normal and tumor cells and competitively blocks cellular action of EGF and other ligands (e.g., transforming growth factor [TGF]-α).1 2 3 5 6 7 8

  • Interaction of EGFR with its normal ligands (e.g., EGF, TGF-α) results in phosphorylation and activation of a series of intracellular proteins that, in turn, regulate transcription of genes involved with cellular growth and survival, motility, and proliferation.1 Signal transduction through EGFR leads to activation of the wild-type (nonmutated) KRAS gene.1 However, the presence of an activating somatic mutation of the KRAS gene (mutated KRAS) in a cancer cell can lead to dysregulation of signaling pathways and resistance to EGFR inhibitor therapy (e.g., cetuximab, panitumumab).1 33

  • Binding of panitumumab to EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis (programmed cell death), decreased proinflammatory cytokine and vascular endothelial growth factor production, and internalization of the EGFR.1 2 5 6

  • In vitro tests and in vivo animal studies suggest that panitumumab may inhibit growth and survival of tumor cells that overexpress EGFR.1 2 5 6 31

Advice to Patients

  • Risk of adverse dermatologic effects, infusion-related reactions (e.g., fever, chills, or breathing problems), pulmonary fibrosis, and potential embryofetal lethality.1 12 13 16 17

  • Importance of informing patients to report persistent or recurrent coughing, wheezing, dyspnea, or new onset facial swelling.1

  • Importance of informing patients to report diarrhea and dehydration to a healthcare professional.1

  • Importance of informing patients to report skin, ocular or visual changes to a healthcare professional.1 16

  • Importance of informing patients to use sunscreen and hats and limit sun exposure during therapy and for 2 months following the last dose of the drug to avoid exacerbation of adverse dermatologic effects.1 7 12 17

  • Importance of advising patients that periodic monitoring of serum electrolytes (including magnesium and calcium) is required.1 16 22

  • Necessity of advising men and women to use an effective method of contraception during panitumumab therapy and for 6 months following the last dose of the drug; women should avoid breast-feeding during therapy and for 2 months following discontinuance of the drug.1 16 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; panitumumab may affect ability of women to become pregnant.1 16 If pregnancy occurs, advise patient of risk to the fetus and/or the potential risk for loss of the pregnancy.1 16

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses, particularly pulmonary disease.1 16

  • Importance of informing patients of other important precautionary information.1 16 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Panitumumab (Recombinant)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

20 mg/mL (100, 200, and 400 mg)

Vectibix

Amgen

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Vectibix 100MG/5ML Solution (AMGEN): 5/$951.99 or 15/$2,706.87

Vectibix 400MG/20ML Solution (AMGEN): 20/$4,349.40 or 60/$12,943.10

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Amgen Inc. Vectibix (panitumumab) injection for intravenous use prescribing information. Thousand Oaks, CA; 2009 Jul.

2. Hoy SM, Wagstaff AJ. Panitumumab in the treatment of metastatic colorectal cancer. Drugs. 2006; 66:2005-14; discussion 2015-6. [PubMed 17100412]

3. Gibson TB, Ranganathan A, Grothey A. Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clin Colorectal Cancer. 2006; 6:29-31. [PubMed 16796788]

4. Peeters M, Van Cutsem E, Siena S et al. A phase 3, multicenter, randomized controlled trial (RCT) of panitumumab plus best supportive care (BSC) vs BSC alone in patients (pts) with metastatic colorectal cancer (mCRC). Oral presentation at 97th Annual Meeting of the American Association for Cancer Research. Washington, DC: 2006 Apr 1-5.

5. Cohenuram M, Saif MW. Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anti-cancer Drugs. 2007; 18:7-15. [PubMed 17159497]

6. Yang XD, Jia XC, Corvalan JR et al. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001; 38:17-23. [PubMed 11255078]

7. Saif MW, Cohenuram M. Role of panitumumab in the management of metastatic colorectal cancer. Clin Colorectal Cancer. 2006; 6:118-24. [PubMed 16945167]

8. Wainberg Z, Hecht JR. Panitumumab in colon cancer: a review and summary of ongoing trials. Expert Opin Biol Ther. 2006; 6:1229-35. [PubMed 17049019]

9. Anon. Panitumumab (Vectibix) for metastatic colorectal cancer. Medical Letter. 2007; 49:35-6. [PubMed 17450113]

10. National Comprehensive Cancer Network (NCCN). Colon and rectal cancer: treatment guidelines for patients. Accessed from the NCCN website.

11. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: colon cancer. Version 2.2007. Accessed from the NCCN website.

12. Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncology. 2005; 16:1425-33.

13. Van Cutsem E, Peeters M, Siena S et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007; 25:1658-64. [PubMed 17470858]

14. Hecht JR, Patnaik A, Berlin J et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer. 2007; 110:980-8. [PubMed 17671985]

15. Lenz H-J. Management and preparedness for infusion and hypersensitivity reactions. The Oncologist. 2007; 12:601-9. [PubMed 17522249]

16. US Food and Drug Administration. Panitumumab (marketed as Vectibix) patient information sheet. 2006 Sep 27.

17. Berlin J, Posey J, Tchekmedyian S et al. Panitumumab with irinotecan/leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer. Clin Colorectal Cancer. 2007; 6:427-32. [PubMed 17531105]

18. Amgen. Amgen discontinues Vectibix treatment in PACCE trial evaluating Vectibix as part of triple combination regimen: preliminary pre-planned interim analysis shows negative effect on progression-free survival. Thousand Oaks, CA; 2007 Mar 22. Press release.

19. Heun J, Holen K . Treatment with panitumumab after a severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer: a case report. Clin Colorectal Cancer. 2007; 6:529-31. [PubMed 17553202]

20. Helbling D, Borner M . Successful challenge with the human EGFR antibody panitumumab following an infusion reaction with the chimeric EGFR antibody cetuximab. Ann Oncology. 2007; 18:963-4.

21. Sartore-Bianchi A, Moroni M, Veronese S et al. Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J Clin Oncol. 2007; 25:3238-45. [PubMed 17664472]

22. Messersmith WA, Hidalgo M . Panitumumab, a monoclonal anti-epidermal growth factor receptor antibody in colorectal cancer: another one or the one?. Clin Cancer Res. 2007; 13:4664-6. [PubMed 17699842]

23. Carrato-Mena A; Study Chair, Spanish Cooperative group for Gastrointestinal Tumor Therapy. Panitumumab in combination with irinotecan chemotherapy as 2nd-line therapy in subjects with mCRC. Protocol ID: TTD-06-04, NCT00475293. Last modified 22 Aug 2007. National Cancer Institute: Clinical Trials (database).

24. Amgen Inc., Thousand Oaks, CA: Personal communication.

25. Mitchell EP, Hecht JR, Baranda J et al. Panitumumab activity in metastatic colorectal cancer (mCRC) patients (pts) with low or negative tumor epidermal growth factor receptor (EGFr) levels: an updated analysis. Paper presented at 2007 ASCO annual meeting. Chicago, IL: 2007 Jun 1-5.

26. Freeman DJ, Juan T, Reiner M et al. Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer. 2008; 7:184-90. [PubMed 18621636]

27. Hecht JR, Mitchell E, Chidiac T, et al. An updated analysis of safety and efficacy of oxaliplatin (ox)/bevacizumab (bev) +/- panitumumab (pmab) for 1st-line treatment (tx) of metastatic colorectal cancer (mCRC) from a randomized, controlled trial (PACCE). Poster presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 25-27, 2008, Orlando, FL.

28. Hecht JR, Mitchell E, Chidiac T, et al. Interim results from PACCE: Irinotecan (iri)/bevacizumab (bev) +/- panitumumab (pmab) as first-line treatment (tx) for metastatic colorectal cancer (mCRC). Poster preseted at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 25-27, 2008, Orlando, FL.

29. Santini D, Loupakis F, Vincenzi B et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist. 2008; 13:1270-5. [PubMed 19056857]

30. Di Nicolantonio F, Martini M, Molinari F et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26:5705-12. [PubMed 19001320]

31. Peeters M, Balfour J, Arnold D. Review article: panitumumab--a fully human anti-EGFR monoclonal antibody for treatment of metastatic colorectal cancer. Aliment Pharmacol Ther. 2008; 28:269-81. [PubMed 19086328]

32. Weber J, McCormack PL. Panitumumab: in metastatic colorectal cancer with wild-type KRAS. BioDrugs. 2008; 22:403-11. [PubMed 18998757]

33. Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26:1626-34. [PubMed 18316791]

34. Chu E. Dual biologic therapy in the first-line mCRC setting: implications of the CAIRO2 study. Clin Colorectal Cancer. 2008; 7:226. [PubMed 18650190]

35. Goodin S. Development of monoclonal antibodies for the treatment of colorectal cancer. Am J Health Syst Pharm. 2008; 65:S3-7; quiz S22-4.

36. Hecht JR. Current and emerging therapies for metastatic colorectal cancer: applying research findings to clinical practice. Am J Health Syst Pharm. 2008; 65:S15-21; quiz S22-4. [PubMed 18499885]

37. Giusti RM, Shastri K, Pilaro AM et al. U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Clin Cancer Res. 2008; 14:1296-302. [PubMed 18316547]

38. Rivera F, Vega-Villegas ME, Lopez-Brea MF et al. Current situation of Panitumumab, Matuzumab, Nimotuzumab and Zalutumumab. Acta Oncol. 2008; 47:9-19. [PubMed 18097777]

39. Hecht JR, Mitchell E, Chidiac T et al. A Randomized Phase IIIB Trial of Chemotherapy, Bevacizumab, and Panitumumab Compared With Chemotherapy and Bevacizumab Alone for Metastatic Colorectal Cancer. J Clin Oncol. 2008; 27:672-80. [PubMed 19114685]

40. Freeman DJ, Juan T, Reiner M et al. Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer. 2008; 7:184-90. [PubMed 18621636]

41. Lacouture ME, Mitchell EP, Shearer H et al. Impact of pre-emptive skin toxicity (ST) treatment (tx) on panitumumab (pmab)-related skin toxicities and quality of life (QOL) in patients (pts) with metastatic colorectal cancer (mCRC): results from STEPP. Paper presented at the 2009 Gastrointestinal Cancers Symposium. Abstr. No. 291.

42. Tejwani A, Shenhong W, Jia Y et al. Increased risk of high-grade dermatologic toxicities with radiation plus epidermal growth factor receptor inhibitor therapy. Cancer. 2009; 115:1286-99. [PubMed 19170238]

43. Hu JC, Sadeghi P, Pinter-Brown LC et al. Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis, and management. J Am Acad Dermatol. 2007; 56:317-26. [PubMed 17141360]

44. Allegra CJ, Jessup JM, Somerfield MR et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009; 27:2091-6. [PubMed 19188670]

45. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology; colon cancer. Version 2.2009. Accessed from the NCCN website.

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