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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000027
Brief Reports

Obatoclax Mesylate, a Pan–Bcl-2 Inhibitor, in Combination with Docetaxel in a Phase 1/2 Trial in Relapsed Non–Small-Cell Lung Cancer

Chiappori, Alberto MD*; Williams, Charles MD; Northfelt, Donald W. MD; Adams, John W. MD; Malik, Shakun MD§; Edelman, Martin J. MD; Rosen, Peter MD; Van Echo, David A. MD#; Berger, Mark S. MD**; Haura, Eric B. MD*

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Abstract

Introduction:

The proapoptotic small-molecule pan–Bcl-2 inhibitor obatoclax mesylate (GX15-070) may enhance the cytotoxicity of chemotherapy in relapsed/refractory non–small-cell lung cancer (NSCLC).

Methods:

Obatoclax was administered with docetaxel in patients with relapsed or refractory NSCLC— docetaxel as a 1-hour infusion on day 1 and obatoclax as a 24-hour infusion on days 1 and 2—every 3 weeks for up to eight cycles. Four dose levels were evaluated in phase 1 (level 1: docetaxel 55 mg/m2 × 1 and obatoclax 30 mg × 2; levels 2–4: docetaxel 75 mg/m2 and obatoclax 30 mg, 45 mg, or 60 mg × 2) to identify dose-limiting toxicity and a phase 2 dose. In phase 2, response and tolerability were evaluated.

Results:

Eighteen patients were included in phase 1. Two dose-limiting toxicities occurred during cycle 1: one febrile neutropenia each at dose levels 3 and 4. Maximum tolerated dose was not reached; 32 patients (including 3 from phase 1) were treated in phase 2 with docetaxel 75 mg/m2 and obatoclax 60 mg (median 2 cycles). Three patients (11%) had partial responses in phase 2; two demonstrated stable disease lasting 12 weeks or more. Median duration of response was 4.8 months. Overall, median progression-free survival was 1.4 months. Neutropenia (31%), febrile neutropenia (16%), and dyspnea (19%) were the most common grade 3/4 adverse events observed.

Conclusions:

Combined obatoclax mesylate plus docetaxel is tolerable in patients with NSCLC, but response was minimal and neutropenia was a common adverse event.

Copyright © 2013 by the International Association for the Study of Lung Cancer

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