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/m × 1 and obatoclax 30 mg × 2; levels 2-4: docetaxel 75 mg/m 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/m 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.
Original language | English (US) |
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Pages (from-to) | 121-125 |
Number of pages | 5 |
Journal | Journal of Thoracic Oncology |
Volume | 9 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2014 |
Keywords
- Apoptosis
- Efficacy
- Maximum tolerated dose
- Non-small-cell lung cancer
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine