NEW YORK-Panitumumab, a 100% human high-affinity IgG2 monoclonal antibody (MoAb) against the epidermal growth factor receptor (EGFR), appears effective in the treatment of colorectal cancer and is well tolerated, according to Joel Randolph Hecht, MD, director of the Gastrointestinal Oncology Program, UCLA School of Medicine. Dr. Hecht presented recent clinical data on panitumumab in colorectal cancer at the Chemotherapy Foundation Symposium XXII. Panitumumab (formerly known as ABX-EGF, codeveloped by Amgen, Inc., and Abgenix) was created using Abgenix's Xeno- Mouse technology, which, according to the company, "enables the rapid generation and selection of high affinity, fully human antibody product candidates to a variety of disease targets." Phase II Monotherapy Dr. Hecht reviewed his group's ongoing multicenter phase II trial of panitumumab monotherapy, which he had presented at the 2004 ASCO annual meeting (abstract 3511). In that study, the monoclonal antibody was found to have antitumor activity when administered as a single-agent to 148 patients with metastatic colorectal cancer who had failed to respond to chemotherapy with a fluoropyrimidine with or without leucovorin, and irinotecan(Drug information on irinotecan) (Camptosar) or oxaliplatin(Drug information on oxaliplatin) (Eloxatin) or both. EGFR expression was determined by immunohistochemistry. "I personally do not think EGFR staining means anything, but at the time the study was done, we thought it might be significant," he added. Panitumumab was given at 2.5 mg/ kg intravenously over 1 hour, once a week for 8 weeks. "We've now gone beyond this dosage, but that is how this trial was done," Dr. Hecht commented. At least 95% of patients experienced some form of skin rash, but only 3% had grade 3 rash, and no patients had grade 4 rash. Grade 3 fatigue and vomiting were seen in 2% and 1% of patients, respectively. Panitumumab was administered without premedication, with the ex-ception of one patient who experienced a grade 3 infusion-related event. "Response rates were very similar to what has been seen with cetuximab(Drug information on cetuximab) [Erbitux]," Dr. Hecht told ONI. "The overall response rate was 10%," with 13 patients having responded at the time of the first 8-week evaluation, and two patients responding after the second 8-week evaluation (both at week 18). "There was also a reasonable amount of stable disease," he added, "but since 48% of patients were either responders or had stable disease at the first look, median time to progression was only about 2 months." Median overall survival was 7.9 months, and median time to progression was 2.0 months. Noting that some striking clinical responses were seen early in the course of therapy, he added that "some of these patients responded clinically within 1 week." As with trials of cetuximab, there was no correlation between the degree of EGFR staining and response to panitumumab, he said. Phase II With IFL Dr. Hecht also discussed a phase II trial of panitumumab with irinotecan, fluorouracil(Drug information on fluorouracil) (5-FU), and leucovorin (IFL, Saltz regimen) in patients with metastatic colorectal cancer, some results of which were presented at the 29th ESMO (European Society for Medical Oncology) Congress by Jordan Berlin, MD, of Vanderbilt University Medical Center (abstract 265). The first part of this multicenter, open-label, single-arm study included 19 patients who received first-line therapy with panitumumab and standard IFL. Panitumumab 2.5 mg/kg was administered over a 1-hour period weekly in 6-week courses (on days 1, 8, 15, 22, 29, and 36) immediately followed by irinotecan 125 mg/m2, leucovorin 20 mg/m2, and 5-FU 500 mg/m2 on days 1, 8, 15, and 22. The second part is a trial of first-line therapy with panitumumab/FOLFIRI (folinic acid [leucovorin], infusional 5-FU, and irinotecan) in 24 patients. Data for the first part of the study showed an unacceptably high incidence of diarrhea at 84% (grade 3 in 42%) and a 16% incidence of nausea, abdominal pain, dehydration, and hypokalemia. Responses, assessed using RECIST criteria, were comparable to what has been seen in phase II studies of IFL alone and of IFL with cetuximab, "with some stable disease and a very low incidence of progressive disease," Dr. Hecht said. The overall response rate after 6 weeks of therapy was 47% (42% partial response, 5% complete response), with stable disease in 32% of patients at week 6 or later. Median progression-free survival time was 8.2 months.