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

Taofeek K. Owonikoko, Joseph Aisner, Xin Victoria Wang, Suzanne E. Dahlberg, Eric H. Rubin, Suresh S. Ramalingam, Murugesan Gounder, Paul Gregory Rausch, Rita S. Axelrod, Joan H. Schiller

Research output: Contribution to journalArticle

3 Scopus citations

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/m 2) 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.

Original languageEnglish (US)
Pages (from-to)171-180
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume73
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Clinical trial
  • Irinotecan
  • Sequential administration
  • Small cell
  • Survival
  • Topoisomerase
  • Topotecan

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'E5501: Phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer'. Together they form a unique fingerprint.

  • Cite this

    Owonikoko, T. K., Aisner, J., Wang, X. V., Dahlberg, S. E., Rubin, E. H., Ramalingam, S. S., Gounder, M., Rausch, P. G., Axelrod, R. S., & Schiller, J. H. (2014). E5501: Phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer. Cancer Chemotherapy and Pharmacology, 73(1), 171-180. https://doi.org/10.1007/s00280-013-2338-z