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Open-Label, Multicenter, Randomized, Phase III Study Comparing Oral Topotecan/Cisplatin Versus Etoposide/Cisplatin As Treatment for Chemotherapy-Naive Patients With Extensive-Disease Small-Cell Lung Cancer

John R. Eckardt, Joachim von Pawel, Zsolt Papai, Antoaneta Tomova, Valentina Tzekova, Theresa E. Crofts, Sarah Brannon, Paul Wissel, Graham Ross

From The Center for Cancer Care and Research, St Louis, MO; Zentralkrankenhaus Gauting, Gauting bei Muenchen, Germany; Koranyi National Institute of Pulmonology, Budapest, Hungary; Oncology Dispensary, Plovdiv, Bulgaria; University Hospital Tzaritza Joanna, Sofia, Bulgaria; GlaxoSmithKline, Collegeville, PA; GlaxoSmithKline, Harlow, United Kingdom

Address reprint requests to John Eckardt, MD, The Center for Cancer Care and Research, 12855 N Outer Forty Dr, Suite 200, St Louis, MO 63141; jeckardt{at}tcccr.com

PURPOSE: This open-label, randomized, multicenter phase III study compared oral topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin (PE) in patients with untreated extensive-disease small-cell lung cancer (ED-SCLC).

PATIENTS AND METHODS: A total of 784 patients were randomly assigned to either oral topotecan 1.7 mg/m²/d x 5 with IV cisplatin 60 mg/m² on day 5 (n = 389) or IV etoposide 100 mg/m²/d x 3 with IV cisplatin 80 mg/m² on day 1 (n = 395) every 21 days.

RESULTS: Overall survival (primary end point) was similar between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year survival was 31% (95% CI, 27% to 36%) in both groups and the difference of –0.03 (95% CI, –6.53 to 6.47) met the predefined criteria of 10% absolute difference for noninferiority of TC relative to PE. Response rates were similar between groups (TC, 63% v PE, 69%). Time to progression was slightly but statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1 weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred more frequently with PE (84% v 59%), whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%, respectively). Lung Cancer Symptom Scale scores were statistically better with PE, but the differences were small and of debatable clinical significance.

CONCLUSION: Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.

Supported by GlaxoSmithKline, Middlesex, United Kingdom.

Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004, and at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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