Interferon alpha plus 13-cis-retinoic acid modulation of BCL-2 plus paclitaxel for recurrent small-cell lung cancer (SCLC): An Eastern Cooperative Oncology Group study (E6501)

Rathi N. Pillai, Joseph Aisner, Suzanne E. Dahlberg, John S. Rogers, Robert S. DiPaola, Seena Aisner, Suresh S. Ramalingam, Joan H. Schiller

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Patients with recurrent small-cell lung cancer (SCLC) have dismal outcomes. The failure of salvage therapy is due to the possible development of resistance mechanisms, such as the upregulation of the anti-apoptosis protein, Bcl-2. We conducted a phase II study to evaluate if modulation of Bcl-2 with 13-cis-retinoic acid (13-CRA) and interferon alpha could improve response rates when combined with paclitaxel in patients with recurrent SCLC. Methods: Patients with recurrent SCLC and measurable disease were treated with interferon alpha at 6 million units/m2 subcutaneously and 13-CRA 1 mg/kg orally on days 1 and 2 and paclitaxel 75 mg/m2 intravenously on day 2 of each week for 6 weeks of an 8-week treatment cycle. Treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of consent. The primary endpoint was response rate with secondary endpoints of progression-free survival (PFS) and overall survival (OS). Bcl-2 levels were assessed in peripheral blood mononuclear cells (PBMCs). Results: Thirty-seven patients were enrolled; 34 were included in the intention-to-treat analysis as 3 patients were ineligible for the study. There were 3 partial responses (9 %), and 5 patients had stable disease (15 %) as best response. The median PFS was 2 months, and median OS was 6.2 months. Although mean Bcl-2 protein levels decreased with therapy in PBMCs, there was no association between Bcl-2 levels and response rate or survival. Conclusion: Despite sound pre-clinical evidence, the addition of 13-CRA and interferon alpha to paclitaxel did not improve outcomes for recurrent SCLC.

Original languageEnglish
Pages (from-to)177-183
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume74
Issue number1
DOIs
StatePublished - Jul 2014

Bibliographical note

Funding Information:
Acknowledgments this study was conducted by the eastern Cooperative Oncology group (robert l. Comis, M.D., Chair) and supported in part by Public Health Service grants Ca23318, Ca66636, Ca21115, Ca21076 and from the national Cancer Institute, national Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the national Cancer Institute.

Keywords

  • 13-cis-retinoic acid
  • Bcl-2
  • Interferon alpha
  • Small-cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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