Phase 2 trial of paclitaxel, 13-cis retinoic acid, and interferon alfa-2b in the treatment of advanced stage or recurrent cervical cancer

Mihae Song, Robert S. Dipaola, Bernadette M. Cracchiolo, Darlene G. Gibbon, Mira Hellmann, Wilberto Nieves-Neira, Ami Vaidya, Allison R. Wagreich, Weichung J. Shih, Lorna Rodriguez-Rodriguez

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. Materials and Methods: Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m<sup>2</sup>, days 1 to 4, and intravenous paclitaxel, 175 mg/m<sup>2</sup>, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. Results: Thirty-three patients were enrolled between March 2001 and June 2009. Thirtyone patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0Y7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5Y26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. Conclusions: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.

Original languageEnglish (US)
Pages (from-to)1636-1641
Number of pages6
JournalInternational Journal of Gynecological Cancer
Volume24
Issue number9
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

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interferon alfa-2b
Isotretinoin
Paclitaxel
Uterine Cervical Neoplasms
Therapeutics
Confidence Intervals
Drug Therapy
Febrile Neutropenia

Keywords

  • 13-cis retinoic acid
  • Cervical cancer
  • Interferon alfa-2b
  • Paclitaxel

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology
  • Medicine(all)

Cite this

Phase 2 trial of paclitaxel, 13-cis retinoic acid, and interferon alfa-2b in the treatment of advanced stage or recurrent cervical cancer. / Song, Mihae; Dipaola, Robert S.; Cracchiolo, Bernadette M.; Gibbon, Darlene G.; Hellmann, Mira; Nieves-Neira, Wilberto; Vaidya, Ami; Wagreich, Allison R.; Shih, Weichung J.; Rodriguez-Rodriguez, Lorna.

In: International Journal of Gynecological Cancer, Vol. 24, No. 9, 01.11.2014, p. 1636-1641.

Research output: Contribution to journalArticle

Song, M, Dipaola, RS, Cracchiolo, BM, Gibbon, DG, Hellmann, M, Nieves-Neira, W, Vaidya, A, Wagreich, AR, Shih, WJ & Rodriguez-Rodriguez, L 2014, 'Phase 2 trial of paclitaxel, 13-cis retinoic acid, and interferon alfa-2b in the treatment of advanced stage or recurrent cervical cancer', International Journal of Gynecological Cancer, vol. 24, no. 9, pp. 1636-1641. https://doi.org/10.1097/IGC.0000000000000258
Song, Mihae ; Dipaola, Robert S. ; Cracchiolo, Bernadette M. ; Gibbon, Darlene G. ; Hellmann, Mira ; Nieves-Neira, Wilberto ; Vaidya, Ami ; Wagreich, Allison R. ; Shih, Weichung J. ; Rodriguez-Rodriguez, Lorna. / Phase 2 trial of paclitaxel, 13-cis retinoic acid, and interferon alfa-2b in the treatment of advanced stage or recurrent cervical cancer. In: International Journal of Gynecological Cancer. 2014 ; Vol. 24, No. 9. pp. 1636-1641.
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abstract = "Objective: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. Materials and Methods: Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m2, days 1 to 4, and intravenous paclitaxel, 175 mg/m2, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. Results: Thirty-three patients were enrolled between March 2001 and June 2009. Thirtyone patients were eligible for evaluation of treatment response. Twenty-seven patients (82{\%}) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30{\%} (6 complete responses and 4 partial responses). Furthermore, 7 patients (21{\%}) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48{\%}]), febrile neutropenia (n = 1 [3{\%}]), and anemia (n = 1 [3{\%}]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95{\%} confidence interval, 2.0Y7.4 months), and overall survival was 11.2 months (95{\%} confidence interval, 7.5Y26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. Conclusions: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.",
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AU - Song, Mihae

AU - Dipaola, Robert S.

AU - Cracchiolo, Bernadette M.

AU - Gibbon, Darlene G.

AU - Hellmann, Mira

AU - Nieves-Neira, Wilberto

AU - Vaidya, Ami

AU - Wagreich, Allison R.

AU - Shih, Weichung J.

AU - Rodriguez-Rodriguez, Lorna

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N2 - Objective: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. Materials and Methods: Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m2, days 1 to 4, and intravenous paclitaxel, 175 mg/m2, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. Results: Thirty-three patients were enrolled between March 2001 and June 2009. Thirtyone patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0Y7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5Y26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. Conclusions: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.

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