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Phase 2 Study of ABT-510 in Patients with Previously Untreated Advanced Renal Cell Carcinoma

Authors' Affiliations: ¹ Arizona Cancer Center, Tucson, Arizona; ² University of Michigan Medical Center, Ann Arbor, Michigan; ³ M. D. Anderson Cancer Center, Houston, Texas; ⁴ Premiere Oncology of Arizona, Scottsdale, Arizona; ⁵ University of Chicago Medical Center, Chicago, Illinois; ⁶ Abbott Laboratories, Abbott Park, Illinois; and ⁷ City of Hope Comprehensive Cancer Center, Duarte, California

Requests for reprints: Scot Ebbinghaus, Merck Research Laboratories, UG4D-72, P.O. Box 1000, North Wales, PA 19454-1099. Phone: 267-305-1279; Fax: 267-305-6537; E-mail: Scot_Ebbinghaus{at}merck.com.

Purpose: Angiogenesis is a characteristic of renal cell carcinoma. ABT-510 is an angiogenesis inhibitor that mimics the antiangiogenic properties of thrombospondin-1. This study was designed to assess the safety and efficacy of ABT-510 in patients with advanced renal cell carcinoma.

Experimental Design: Patients with previously untreated metastatic or unresectable renal cell carcinoma were randomized to treatment with one of two doses of ABT-510, self-administered s.c. twice daily in 28-day treatment periods without intervening rest periods. End points were progression-free survival (PFS), objective response rate, overall survival, and toxicity.

Results: The objective response rate was 4% in the 10 mg twice daily group, and there were two unconfirmed PRs in the 100 mg twice daily group. Respective median PFS was 4.2 and 3.3 months, with a 6-month PFS of 39% and 32%. Median overall survival was 27.8 months (10 mg twice daily) and 26.1 months (100 mg twice daily). The most frequent adverse events were injection site reactions (84%), fatigue (50%), headache (20%), and nausea (19%). The incidence of treatment-related, grade 3/4 adverse events was low and included three bleeding episodes (gastrointestinal hemorrhage, intracranial hemorrhage, and hemoptysis) and one thrombotic event (deep vein thrombosis). No deaths were attributed to ABT-510.

Conclusions: There was little evidence of clinical activity for ABT-510, and further evaluation as a single agent for treating advanced renal cell carcinoma is not warranted. The evidence of a favorable safety profile may justify further evaluation in combination therapy.

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