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 Citations (Scopus)

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

Fingerprint

irinotecan
Topotecan
Small Cell Lung Carcinoma
Etoposide
Cisplatin
Topoisomerase Inhibitors
Cells
Topoisomerase II Inhibitors
Type I DNA Topoisomerase
Chemotherapy
Platinum
Brain
Disease-Free Survival
Neoplasm Metastasis
Drug Therapy

Keywords

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

ASJC Scopus subject areas

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

Cite this

E5501 : Phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer. / Owonikoko, Taofeek K.; Aisner, Joseph; Wang, Xin Victoria; Dahlberg, Suzanne E.; Rubin, Eric H.; Ramalingam, Suresh S.; Gounder, Murugesan; Rausch, Paul Gregory; Axelrod, Rita S.; Schiller, Joan H.

In: Cancer Chemotherapy and Pharmacology, Vol. 73, No. 1, 01.2014, p. 171-180.

Research output: Contribution to journalArticle

Owonikoko, TK, Aisner, J, Wang, XV, Dahlberg, SE, Rubin, EH, Ramalingam, SS, Gounder, M, Rausch, PG, Axelrod, RS & Schiller, JH 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, vol. 73, no. 1, pp. 171-180. https://doi.org/10.1007/s00280-013-2338-z
Owonikoko, Taofeek K. ; Aisner, Joseph ; Wang, Xin Victoria ; Dahlberg, Suzanne E. ; Rubin, Eric H. ; Ramalingam, Suresh S. ; Gounder, Murugesan ; Rausch, Paul Gregory ; Axelrod, Rita S. ; Schiller, Joan H. / E5501 : Phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer. In: Cancer Chemotherapy and Pharmacology. 2014 ; Vol. 73, No. 1. pp. 171-180.
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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/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.",
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T2 - Phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer

AU - Owonikoko, Taofeek K.

AU - Aisner, Joseph

AU - Wang, Xin Victoria

AU - Dahlberg, Suzanne E.

AU - Rubin, Eric H.

AU - Ramalingam, Suresh S.

AU - Gounder, Murugesan

AU - Rausch, Paul Gregory

AU - Axelrod, Rita S.

AU - Schiller, Joan H.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

KW - Clinical trial

KW - Irinotecan

KW - Sequential administration

KW - Small cell

KW - Survival

KW - Topoisomerase

KW - Topotecan

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