This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ardizzoni, A. Articles by King, K. Search for Related Content PubMed PubMed Citation Articles by Ardizzoni, A. Articles by King, K.

European Organization for Research and Treatment of Cancer (EORTC) 08957 Phase II Study of Topotecan in Combination with Cisplatin as Second-Line Treatment of Refractory and Sensitive Small Cell Lung Cancer¹

Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa, Italy [A. A., C. N.]; Thoraxklinik, D-69126 Rohrbach, Germany [C. M., E. B.]; European Organization for Research and Treatment of Cancer Data Center, B-1200 Brussels, Belgium [C. D., C. L.]; National Cancer Institute, Cairo 11796, Egypt [R. G.]; Free University, NL-1081 Amsterdam, the Netherlands [E. F. S., G. G.]; 12 de Octubre Hospital, E-28041 Madrid, Spain [P. L.]; Academisch Ziekenhuis, NL-6202 Maastricht, the Netherlands [G. t. V.]; Centre Hospitalier Regional de la Citadelle, B-4000 Liege, Belgium [L. B.]; and GlaxoSmithKline Pharmaceuticals, Greenford UB6 OHE, United Kingdom [K. K.]

Purpose: The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in "sensitive" (s) and "refractory" (r) small-cell lung cancer (SCLC) patients treated previously.

Experimental Design: Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study. Patients were enrolled in two separate groups: r group (patients who failed first-line treatment <3 months from treatment discontinuation) and s group (patients who responded to first-line treatment and progressed 3 months after treatment discontinuation). Cisplatin was given i.v. at the dose of 60 mg/m² on day 1, and topotecan was administered as a daily i.v. infusion at the dose of 0.75 mg/m² from day 1 to 5, every 3 weeks.

Results: A total of 110 eligible (68 s and 42 r) patients were enrolled from 24 institutions. The main patient characteristics were as follows: median age 60 (s) and 55 (r) years, median performance status 1 for both (s) and (r). Seventy-four percent (s) and 67% (r) had extensive stage disease, including 22% and 36%, respectively, with brain metastases. A total of 398 chemotherapy courses were administered [median 4 (s) and 3 (r) per patient]. The most frequent and serious toxicity was myelosuppression. Grade IV neutropenia occurred in 62% (s) and 49% (r) of patients, with a 19% (s) and 15% (r) incidence of febrile neutropenia, and grade IV thrombocytopenia in 54% (s) and 44% (r). Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and/or delay in the following courses. Grade III-IV nonhematological toxicity was uncommon. Five deaths possibly related to toxicity occurred among s patients only. Objective responses have been documented in 20 s patients, 19 partial responses and 1 complete response, (29.4% response rate; 95% confidence interval, 19–42), whereas, among r patients, 10 partial responses have been observed (23.8% response rate; 95% confidence interval, 12–39). Median survival for s and r was 6.4 and 6.1 months, respectively.

Conclusions: The combination of cisplatin and topotecan, at this dose and schedule, shows activity and promising results in patients with refractory SCLC, with reversible myelosuppression being the main side effect. Additional development of this regimen, using better-tolerated schedules, is warranted in patients with refractory SCLC.

This article has been cited by other articles:

				J. R. Eckardt, J. von Pawel, Z. Papai, A. Tomova, V. Tzekova, T. E. Crofts, S. Brannon, P. Wissel, and G. Ross 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 J. Clin. Oncol., May 1, 2006; 24(13): 2044 - 2051. [Abstract] [Full Text] [PDF]

				S. J. Antonia, N. Mirza, I. Fricke, A. Chiappori, P. Thompson, N. Williams, G. Bepler, G. Simon, W. Janssen, J.-H. Lee, et al. Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer Clin. Cancer Res., February 1, 2006; 12(3): 878 - 887. [Abstract] [Full Text] [PDF]

				A. Ardizzoni Topotecan in the Treatment of Recurrent Small Cell Lung Cancer: An Update Oncologist, December 1, 2004; 9(suppl_6): 4 - 13. [Abstract] [Full Text] [PDF]

				D. J. Stewart Update on the Role of Topotecan in the Treatment of Non-Small Cell Lung Cancer Oncologist, December 1, 2004; 9(suppl_6): 43 - 52. [Abstract] [Full Text] [PDF]

				J. V. Heymach, D. H. Johnson, F. R. Khuri, H. Safran, L. L. Schlabach, F. Yunus, R. F. DeVore III, P. M. De Porre, H. M. Richards, X. Jia, et al. Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung cancer Ann. Onc., August 1, 2004; 15(8): 1187 - 1193. [Abstract] [Full Text] [PDF]