Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 4112
© 2008 American Society of Clinical Oncology

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Abstract

Axitinib (AG-013736) in combination with FOLFOX and bevacizumab (Bev) in patients (pts) with metastatic solid tumors: A phase I study

Eastern Carolina Internal Medicine, Pollocksville, NC; Nevada Cancer Institute, Las Vegas, NV; St. Francis Cancer Care Center, Indianapolis, IN; Bay Area Cancer Research Group, Concord, CA; Pfizer Global Research and Development, San Diego, CA

4112

Background: Axitinib is an oral, potent and selective inhibitor of VEGF receptors 1, 2, and 3 that is being assessed in a broad range of tumors. This phase I portion of the study evaluated the safety and pharmacokinetics (PK) of axitinib in combination with BV and FOLFOX (oxaliplatin/5-fluorouracil [5-FU]/leucovorin) in pts with previously treated gastrointestinal and solid tumors. Methods: Pts in cohort 1 received BV 1 mg/kg, oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU 400 mg/m² bolus then 2,400 mg/m² by 46–48 h infusion, and axitinib at a starting dose of 5 mg PO BID. BV and FOLFOX were administered once every 2 weeks. Following demonstration of tolerability to BV 1 mg/kg in cohort 1, BV was escalated to doses of 2 mg/kg and 5 mg/kg in cohorts 2 and 3 respectively. Patients were evaluated for potential PK interactions between BV, FOLFOX, and axitinib. Safety and tumor response were also assessed. Results: Among pts enrolled in cohorts 1, 2, and 3 (n=15), 2 patients (13%) showed a partial response and 9 patients (60%) exhibited stable disease. The most frequently reported, treatment-emergent grade 3–5 adverse events were neutropenia (n=3), hypertension (n=3), and dyspnea (n=2). PK parameters and plasma profiles of BV, oxaliplatin, and 5-FU were similar in the presence or absence of axitinib, with mean (%CV) AUC_inf for platinum clearance from ultrafiltrate of 7,155 ng.h/mL (74%) and 7,702 ng.h/mL (72%), respectively (n=14). Axitinib PK profiles were similar in the presence or absence of BV/FOLFOX. Conclusions: PK data indicate no evidence of an interaction between axitinib and BV/FOLFOX. Axitinib 5 mg BID in combination with BV 1 mg/kg or 2 mg/kg and FOLFOX was well tolerated. Tolerability data for combination treatment with the 5 mg BV dose await completion of patient enrollment into cohort 3. A 3-arm, randomized phase II study of axitinib/FOLFOX vs BV/FOLFOX vs axitinib/BV/FOLFOX in pts with metastatic colorectal cancer has been initiated.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer

Abstract presentation from the 2008 ASCO Annual Meeting