This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rudin, C. M. Articles by Vokes, E. E. Search for Related Content PubMed PubMed Citation Articles by Rudin, C. M. Articles by Vokes, E. E.

Randomized Phase II Study of Carboplatin and Etoposide With or Without the bcl-2 Antisense Oligonucleotide Oblimersen for Extensive-Stage Small-Cell Lung Cancer: CALGB 30103

Charles M. Rudin, Ravi Salgia, Xiaofei Wang, Lydia D. Hodgson, Gregory A. Masters, Mark Green, Everett E. Vokes

From the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; Department of Medicine, University of Chicago, Chicago, IL; Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham, NC; Helen F. Graham Cancer Center, Christiana Care Health Services Inc, Wilmington, DE; Division of Hematology/Oncology, Department of Medicine and Hollings Cancer Center, Medical University of South Carolina, Charleston, SC

Corresponding author: Charles Rudin, MD, PhD, Sidney Kimmel Comprehensive Cancer Center, David H. Koch Cancer Research Building, Suite 544, 1550 Orleans St, Baltimore, MD 21231; e-mail: rudin{at}jhmi.edu

Purpose: To assess the efficacy and toxicity of carboplatin, etoposide, and the bcl-2 antisense oligonucleotide oblimersen as initial therapy for extensive-stage small-cell lung cancer (ES-SCLC). bcl-2 has been implicated as a key factor in SCLC oncogenesis and chemotherapeutic resistance.

Patients and Methods: A 3:1 randomized phase II study was performed to evaluate carboplatin and etoposide with (arm A) or without oblimersen (arm B) in 56 assessable patients with chemotherapy-naïve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failure-free survival, overall survival, and 1-year survival rate.

Results: Oblimersen was associated with slightly more grade 3 to 4 hematologic toxicity (88% v 60%; P = .05). Response rates were 61% (95% CI, 45% to 76%) for arm A and 60% (95% CI, 32% to 84%) for arm B. The percentage of patients alive at 1 year was 24% (95% CI, 12% to 40%) with oblimersen, and 47% (95% CI, 21% to 73%) without oblimersen. Hazard ratios for failure-free survival (1.79; P = .07) and overall survival (2.13; P = .02) suggested worse outcome for patients receiving oblimersen. These results hold when adjusted for other prognostic factors, such as weight loss, in multivariate regression analysis.

Conclusion: Despite extensive data supporting a critical role for Bcl-2 in chemoresistance in SCLC, addition of oblimersen to a standard regimen for this disease did not improve any clinical outcome measure. Emerging data from several groups suggest that this lack of efficacy may be due to insufficient suppression of Bcl-2 in vivo. Additional evaluation of this agent in SCLC is not warranted.

The research for CALGB 30103 was supported in part by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B and to the CALGB Statistical Center (CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Additional support information to individual participating institutions appears in the Acknowledgment (online only).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				B. E. Johnson, C. M. Rudin, and R. Salgia Novel and Targeted Agents for Small Cell Lung Cancer ASCO Educational Book, January 1, 2008; 2008(1): 363 - 367. [Abstract] [Full Text] [PDF]