This Article Full Text Full Text (PDF) Erratum (v25,p3387) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eckardt, J. R. Articles by Ross, G. Search for Related Content PubMed PubMed Citation Articles by Eckardt, J. R. Articles by Ross, G.

Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer

John R. Eckardt, Joachim von Pawel, Jean-Louis Pujol, Zsolt Papai, Elisabeth Quoix, Andrea Ardizzoni, Ruth Poulin, Alaknanda J. Preston, Graham Dane, Graham Ross

From the Center for Cancer Care and Research, St Louis, MO; Asklepios Klinik, Gauting bei Muenchen, Germany; Hôpital Arnaud de Villeneuve, Montpellier; University Hospital, Strasbourg, France; St George County Hospital, Székesfehérvár, Hungary; University Hospital, Parma, Italy; GlaxoSmithKline, Collegeville, PA; and GlaxoSmithKline, Harlow, United Kingdom

Address reprint requests to John R. Eckardt, MD, Center for Cancer Care and Research, 12855 N Outer Fourty Rd, Ste 200, St Louis, MO 63141; e-mail: jeckardt{at}tcccr.com

Purpose: Single-agent intravenous (IV) topotecan is an effective treatment for small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open-label, randomized, phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy.

Patients and Methods: Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of 90 days were assigned to treatment with either oral topotecan 2.3 mg/m²/d on days 1 through 5 or IV topotecan 1.5 mg/m²/d on days 1 through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment.

Results: A total of 309 patients were randomly assigned. In intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153) and 21.9% with IV topotecan (n = 151), with a difference (oral –IV) of –3.6% (95% CI, –12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third-line chemotherapy was similar for both groups (33% for oral; 35% for IV). Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3 or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most frequent nonhematologic adverse events (all grades) included nausea (43% oral; 42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea (36% oral; 20% IV).

Conclusion: Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.

Research funded by GlaxoSmithKline, Middlesex, United Kingdom.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31 to June 3, 2003.

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

This article has been cited by other articles:

				D. H. Lee, S.-W. Kim, C. Suh, J.-S. Lee, J. H. Lee, S.-J. Lee, B. Y. Ryoo, K. Park, J. S. Kim, D. S. Heo, et al. Belotecan, new camptothecin analogue, is active in patients with small-cell lung cancer: results of a multicenter early phase II study Ann. Onc., January 1, 2008; 19(1): 123 - 127. [Abstract] [Full Text] [PDF]

				M. O'Brien, J. Eckardt, and R. Ramlau Recent Advances with Topotecan in the Treatment of Lung Cancer Oncologist, October 1, 2007; 12(10): 1194 - 1204. [Abstract] [Full Text] [PDF]