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Clinical Trial
. 2014 Jul;74(1):177-83.
doi: 10.1007/s00280-014-2427-7. Epub 2014 May 24.

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  1 , Joseph Aisner, Suzanne E Dahlberg, John S Rogers, Robert S DiPaola, Seena Aisner, Suresh S Ramalingam, Joan H Schiller
Affiliations
Clinical Trial

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 et al. Cancer Chemother Pharmacol. 2014 Jul.

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.

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Figures

Figure 1
Figure 1
Enrollment and follow-up of patients in the E6501 study.
Figure 2
Figure 2
Progression-free survival in eligible patients.
Figure 3
Figure 3
Overall survival in eligible patients.
See this image and copyright information in PMC

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