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

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/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) 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.

• Authors: 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
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 73 Issue 1 Pg. 171-80 (Jan 2014) ISSN: 1432-0843 [Electronic] Germany
• PMID: 24288121 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Topoisomerase I Inhibitors
• Topoisomerase II Inhibitors
• Etoposide
• Irinotecan
• Topotecan
• Cisplatin
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Cisplatin (administration & dosage)
• Etoposide (administration & dosage)
• Female
• Humans
• Irinotecan
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Small Cell Lung Carcinoma (drug therapy, mortality, pathology)
• Topoisomerase I Inhibitors (administration & dosage)
• Topoisomerase II Inhibitors (administration & dosage)
• Topotecan (administration & dosage)