PHILADELPHIABevacizumab (Avastin), a monoclonal antibody against vascular endothelial growth factor (VEGF), was well tolerated in preliminary analyses of two Eastern Cooperative Oncology Group (ECOG) studies, according to Bruce J. Giantonio, MD, assistant professor of medicine, University of Pennsylvania Medical Center, Philadelphia.
Combination therapy with irinotecan(Drug information on irinotecan) (CPT-11, Camptosar), fluorouracil(Drug information on fluorouracil) (5-FU), leucovorin (IFL) required reduction of irinotecan doses from 125 mg/m2 to 100 mg/m2 and of 5-FU from 500 mg/m2 to 400 mg/m2 in combination therapy, but bevacizumab(Drug information on bevacizumab) did not increase the risk of thrombosis. The reductions of the starting doses of irinotecan and 5-FU were enacted as a result of the toxicity analyses conducted on other trials using IFL and not as a result of toxicities seen in this trial (E2200).
The phase II study enrolled patients with histologically confirmed advanced or metastatic adenocarcinoma of the colon or rectum. Patients had no prior therapy for advanced disease, but prior 5-FU adjuvant therapy was allowed if it had occurred more than 1 year before study entry. Patients were treated with IFL every week for 4 weeks and with bevacizumab (10 mg/kg IV) every 14 days. Accrual was suspended at 92 patients in February 2002. Dr. Giantonio reported toxicity data on 60 patients, including 19 accrued prior to the dosage reduction.
Toxicity Profile Unaltered
"Gastrointestinal toxicities were common and not unexpected," Dr. Giantonio said. "Diarrhea was mostly grade 1 or 2 (67%); 15% of patients had grade 3 diarrhea; and there was no grade 4 diarrhea. Grade 1 or 2 vomiting occurred in 18% of patients, grade 3 in 12%, and grade 4 in 2%. Grade 1 or 2 nausea occurred in 59%, and grade 3 in 12%. Dehydration was grade 1 in 2% of patients, grade 3 in 5%, and grade 4 in 2%."
Neutropenia was the worst hematologic toxicity. Grade 1 or 2 neutropenia occurred in 43% of patients, grade 3 in 15%, and grade 4 in 18%. Grade 3 febrile neutropenia occurred in 5% of patients and infection with grade 3 or grade 4 neutropenia in 2%.
Thrombocytopenia was relatively rare, with grade 1 or 2 occurring in 20% of patients. "There were 21 bleeding events reported, 19 of which were grade 1 and predominantly epistaxis. Only one event required transfusions," Dr. Giantonio said. There were no treatment-related deaths in trial E2200.