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Adding Bevacizumab to IFL Combination Does Not Significantly Alter IFL Toxicity

Adding Bevacizumab to IFL Combination Does Not Significantly Alter IFL Toxicity

PHILADELPHIA—Bevacizumab (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 (CPT-11, Camptosar), 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 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.

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