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E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer

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Abstract

Purpose

Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC).

Methods

Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0–3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m2) on days 1, 2 and 3, etoposide (70 mg/m2) and cisplatin (20 mg/m2) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m2) and cisplatin (20 mg/m2) on days 1 and 8 followed by etoposide (85 mg/m2 PO bid) on days 3 and 10 (PIE) in a 3-week cycle.

Results

We enrolled 140 patients and randomized 66 eligible patients to each arm. Only 54.5 % of all patients completed the planned maximum 6 cycles. There were grade ≥3 treatment-related adverse events in approximately 70 % of the patients on both arms including 6 treatment-related grade 5 events. The overall response rates (CR + PR) were 69.7 % (90 % CI 59.1–78.9, 95 % CI 57.1–80.4 %) for arm A and 57.6 % (90 % CI 46.7–67.9, 95 % CI 44.8–69.7 %) for arm B. The median progression-free survival and overall survival were 6.4 months (95 % CI 5.4–7.5 months) and 11.9 months (95 % CI 9.6–13.7 months) for arm A and 6.0 months (95 % CI 5.4–7.0 months) and 11.0 months (95 % CI 8.6–13.1 months) for arm B.

Conclusion

Sequential administration of topoisomerase inhibitors did not improve on the historical efficacy of standard platinum-doublet chemotherapy for extensive-stage SCLC.

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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, CA107868, CA16116, CA13650 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

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Authors and Affiliations

  1. Emory University, Atlanta, GA, USA

    Taofeek K. Owonikoko & Suresh S. Ramalingam

  2. Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901-1914, USA

    Joseph Aisner & Murugesan Gounder

  3. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    Xin Victoria Wang & Suzanne E. Dahlberg

  4. Department of Biostatistics, Dana–Farber Cancer Institute, Boston, MA, USA

    Xin Victoria Wang & Suzanne E. Dahlberg

  5. Merck Research Laboratories, North Wales, PA, USA

    Eric H. Rubin

  6. Frederick Memorial Hospital, Frederick, MA, USA

    Paul Gregory Rausch

  7. Thomas Jefferson University, Philadelphia, PA, USA

    Rita S. Axelrod

  8. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Joan H. Schiller

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  1. Taofeek K. Owonikoko
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  2. Joseph Aisner
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  3. Xin Victoria Wang
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  10. Joan H. Schiller
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Correspondence to Joseph Aisner.

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Owonikoko, T.K., Aisner, J., Wang, X.V. et al. E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer. Cancer Chemother Pharmacol 73, 171–180 (2014). https://doi.org/10.1007/s00280-013-2338-z

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  • DOI: https://doi.org/10.1007/s00280-013-2338-z

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