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

Research output: Contribution to journalArticle

Abstract

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-na?̈ve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failurefree 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.

Original languageEnglish (US)
Pages (from-to)870-876
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number6
DOIs
StatePublished - Feb 20 2008

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Antisense Oligonucleotides
Carboplatin
Small Cell Lung Carcinoma
Etoposide
Survival
Survival Rate
Outcome Assessment (Health Care)
oblimersen
Weight Loss
Carcinogenesis
Multivariate Analysis
Regression Analysis
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

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

In: Journal of Clinical Oncology, Vol. 26, No. 6, 20.02.2008, p. 870-876.

Research output: Contribution to journalArticle

Rudin, Charles M. ; Salgia, Ravi ; Wang, Xiaofei ; Hodgson, Lydia D. ; Masters, Gregory A. ; Green, Mark ; Vokes, Everett 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. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 6. pp. 870-876.
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abstract = "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-na?̈ve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failurefree 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.",
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T1 - Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer

T2 - CALGB 30103

AU - Rudin, Charles M.

AU - Salgia, Ravi

AU - Wang, Xiaofei

AU - Hodgson, Lydia D.

AU - Masters, Gregory A.

AU - Green, Mark

AU - Vokes, Everett E.

PY - 2008/2/20

Y1 - 2008/2/20

N2 - 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-na?̈ve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failurefree 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.

AB - 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-na?̈ve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failurefree 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.

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