CALGB 30103: A randomized phase II study of carboplatin and etoposide (CE) with or without G3139 in patients with extensive stage small cell lung cancer (ES-SCLC)

Abstract

7168 Background: Bcl-2, an inhibitor of apoptosis associated with chemotherapeutic resistance, is expressed in up to 90% of SCLC. The antisense oligonucleotide G3139 can suppress Bcl-2 levels and increases chemotherapeutic efficacy in preclinical models. A prior phase I clinical trial defined a regimen combining G3139 with CE in patients with ES-SCLC with acceptable toxicity. Methods: This was a two-arm phase II study using 3:1 randomization to CE with (arm A) or without (arm B) G3139 in adults with previously untreated ES-SCLC and ECOG performance status 0–2. Objectives included assessment of % of subjects alive after 12 months, response rate, and toxicity in arm A, as well as comparison of toxicity between arms. Results: Accrual from 7/03 to 10/04 was 63 patients with 47 in arm A and 16 in arm B. Four patients in arm A canceled registration before treatment and are excluded from analysis. Study arms were well balanced for age, gender, race, ethnicity, and performance status. Of 18 patients on arm A currently evaluable for response, objective response was seen in 67% (6% CR, 61% PR). As of 11/24/04, adverse event data were available for 28 patients in arm A and 5 in arm B. There have been 12 deaths on study, 10 in arm A. One death in arm A was due to renal failure and is considered probably treatment related. There is a trend toward increased grade 4+ toxicity in arm A (17/28=61%) compared to arm B (2/5=40%), p=0.11. Most common grade 4 toxicities included neutropenia (43%), thrombocytopenia (14%), and leukopenia(14%). Non-hematologic toxicities were rare. Median follow-up is insufficient to estimate survival time on either arm. Conclusions: Co-administration of G3139 with CE for ES-SCLC is feasible in a multi-institutional context, but may be associated with increased toxicity. Final analysis of adverse events and clinical outcome data, especially survival time, from this study will help define whether this toxicity is counterbalanced by patient benefit. No significant financial relationships to disclose.