Originally published as JCO Early Release 10.1200/JCO.2005.03.6491 on May 8 2006

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Phase III Study Comparing Oral Topotecan to Intravenous Docetaxel in Patients With Pretreated Advanced Non–Small-Cell Lung Cancer

Rodryg Ramlau, Radj Gervais, Maciej Krzakowski, Joachim von Pawel, Eckhard Kaukel, Raymond P. Abratt, Bernie Dharan, Kelly M. Grotzinger, Graham Ross, Graham Dane, Frances A. Shepherd

From the Regional Lung Disease Centre, Oncology Department, Poznan; Centre of Oncology & Institute, Warsaw, Poland; Centre Francois Baclesse, Caen, France; Asklepios Klinik, Gauting bei Muenchen, Munich; Thoraxzentrum, Hamburg, Germany; University of Cape Town, Cape Town, South Africa; GlaxoSmithKline, Collegeville, PA; GlaxoSmithKline, Harlow, United Kingdom; and Princess Margaret Hospital, Toronto, Ontario, Canada

Address reprint requests to Rodryg Ramlau, MD, PhD, Lung Disease Centre, Oncology Department, ul.Szamarzewskiego 62, 60-569 Poznan, Poland; e-mail: rramlau{at}wcchpig.pl

PURPOSE: This open-label, randomized, multicenter, phase III study compared oral topotecan versus intravenous (IV) docetaxel in patients with previously treated non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Patients with stage III or IV NSCLC, performance status 2, who had received only one prior chemotherapy regimen, were randomly assigned to treatment with oral topotecan 2.3 mg/m²/d on days 1 to 5 or IV docetaxel 75 mg/m² day 1 every 21 days.

RESULTS: A total of 829 patients were randomly assigned. In intent-to-treat analysis, 1-year survival rates were 25.1% with topotecan and 28.7% with docetaxel. The difference of –3.6% (95% CI, –9.59% to 2.48%) met the predefined criteria for noninferiority of topotecan relative to docetaxel because the lower limit of the 95% CI was above –10%. Median survival was 27.9 weeks with topotecan and 30.7 weeks with docetaxel. Although not statistically significant (log-rank P = .057), the higher survival rate with docetaxel was maintained across the entire treatment period. The median time to progression was 11.3 weeks with topotecan versus 13.1 weeks with docetaxel (log-rank P = .02). The overall response rate was 5% in each group. Grade 3/4 neutropenia occurred more frequently with docetaxel (60% v 50%). Grade 3/4 anemia and thrombocytopenia occurred more frequently with topotecan (26% v 10% and 26% v 7%, respectively).

CONCLUSION: Oral topotecan provides activity in the treatment of relapsed, locally advanced, unresectable NSCLC. Both regimens were well tolerated with differing safety profiles. Topotecan may provide an option for patients who desire an orally available treatment after relapse.

Supported by GlaxoSmithKline, Middlesex, United Kingdom.

Presented in part 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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