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 journalArticle

14 Citations (Scopus)

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

Fingerprint

Isotretinoin
Oncology
Small Cell Lung Carcinoma
Paclitaxel
Interferon-alpha
Cells
Modulation
Blood
Salvaging
Disease-Free Survival
Toxicity
Blood Cells
Proteins
Acoustic waves
Apoptosis
Salvage Therapy
Intention to Treat Analysis
Survival
Disease Progression
Up-Regulation

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Cancer Chemotherapy and Pharmacology, Vol. 74, No. 1, 2014, p. 177-183.

Research output: Contribution to journalArticle

Pillai, Rathi N. ; Aisner, Joseph ; Dahlberg, Suzanne E. ; Rogers, John S. ; DiPaola, Robert S. ; Aisner, Seena ; Ramalingam, Suresh S. ; Schiller, Joan H. / 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). In: Cancer Chemotherapy and Pharmacology. 2014 ; Vol. 74, No. 1. pp. 177-183.
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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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T1 - Interferon alpha plus 13-cis-retinoic acid modulation of BCL-2 plus paclitaxel for recurrent small-cell lung cancer (SCLC)

T2 - An Eastern Cooperative Oncology Group study (E6501)

AU - Pillai, Rathi N.

AU - Aisner, Joseph

AU - Dahlberg, Suzanne E.

AU - Rogers, John S.

AU - DiPaola, Robert S.

AU - Aisner, Seena

AU - Ramalingam, Suresh S.

AU - Schiller, Joan H.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - 13-cis-retinoic acid

KW - Bcl-2

KW - Interferon alpha

KW - Small-cell lung cancer

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