Panitumumab with irinotecan/leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer.

Abstract

PURPOSE:

Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor and is indicated for patients with metastatic colorectal cancer (mCRC) who have experienced disease progression after standard chemotherapy. We conducted this phase II study to assess the ability of panitumumab to be administered with first-line irinotecan-containing regimens in patients with mCRC.

PATIENTS AND METHODS:

This was a 2-part multicenter study of panitumumab 2.5 mg/kg weekly with irinotecan, 5-fluorouracil (5-FU), and leucovorin. Part 1 used bolus 5-FU (IFL), and part 2 used infusional 5-FU (FOLFIRI). Tolerability (measured by grade 3/4 diarrhea) was the primary endpoint. Objective response, progression-free survival, overall survival, and safety were also examined.

RESULTS:

Nineteen patients in part 1 and 24 patients in part 2 received panitumumab plus chemotherapy. Grade 3/4 diarrhea occurred in 11 patients (58%) in part 1 and 6 patients (25%) in part 2. All patients had a skin-related toxicity (no grade 4 events). Objective response rates were 46% in part 1 and 42% in part 2. Disease control rates were 74% in part 1 and 79% in part 2. Median progression-free survival (95% confidence interval) was 5.6 months (4.4-8.3 months) for part 1 and 10.9 months (7.7-22.5 months) for part 2. Median overall survival (95% confidence interval) was 17 months (13.7 months to not estimable) for part 1 and 22.5 months (14.4 months to not estimable) for part 2.

CONCLUSION:

In patients with mCRC, panitumumab/IFL was not well tolerated. Panitumumab/FOLFIRI was well tolerated, showed promising activity, and is undergoing further investigation.

• Authors: Jordan Berlin, James Posey, Simon Tchekmedyian, Eddie Hu, David Chan, Imtiaz Malik, Liqiang Yang, Rafael G Amado, J Randolph Hecht
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 6 Issue 6 Pg. 427-32 (Mar 2007) ISSN: 1533-0028 [Print] United States
• PMID: 17531105 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Vitamin B Complex
• Panitumumab
• Irinotecan
• ErbB Receptors
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adenocarcinoma (drug therapy, enzymology, pathology)
• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Colorectal Neoplasms (drug therapy, enzymology, pathology)
• ErbB Receptors (antagonists & inhibitors)
• Female
• Fluorouracil (administration & dosage, adverse effects, therapeutic use)
• Humans
• Irinotecan
• Leucovorin (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Neoplasm Metastasis
• Panitumumab
• Vitamin B Complex (administration & dosage, adverse effects)