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Lung Cancer

Recent Advances with Topotecan in the Treatment of Lung Cancer

^aRoyal Marsden Hospital, Surrey, United Kingdom; ^bThe Center for Cancer Care and Research, St. Louis, Missouri, USA; ^cRegional Lung Disease Centre, Oncology Department, Poznan, Poland

Key Words. Lung cancer • Topotecan oral • Chemotherapy

Correspondence: Mary O'Brien, M.D., FRCP, Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM25JS, United Kingdom. Telephone: 00442086613278; Fax: 00442086437371; e-mail: mary.o'brien{at}rmh.nhs.uk

Disclosure: M.O'B. has acted as a consultant to Schering-Plough, Roche, and GlaxoSmithKline. J.E. has a financial interest in Aventis and GlaxoSmithKline. No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

Topotecan is a semisynthetic derivative of camptothecin that specifically targets topoisomerase I. It has well-established antineoplastic properties and has been successfully combined with other antineoplastic agents with activity dependent on DNA disruption, such as cisplatin and etoposide. Topotecan is indicated for the treatment of small cell lung cancer (SCLC) sensitive disease after failure of first-line chemotherapy and metastatic ovarian carcinoma after failure of initial or subsequent chemotherapy. Since the approval of topotecan for the second-line treatment of SCLC, studies have been conducted in the first-line setting. Recent studies demonstrate the utility of i.v. topotecan in combination with cisplatin for untreated SCLC. Further, an oral formulation of topotecan is currently under investigation and may provide added convenience for patients. Oral topotecan has been studied in the first- and second-line settings for both SCLC and non-small cell lung cancer (NSCLC). Three recent phase III trials have demonstrated the activity of oral topotecan. In the first study of chemotherapy-naïve patients with extensive-disease SCLC, oral topotecan plus cisplatin provided efficacy and safety similar to those of etoposide plus cisplatin. In a second study of patients with relapsed SCLC, treatment with oral topotecan showed a statistically significant and clinically meaningful longer overall survival time and improvement in dyspnea and quality of life compared with best supportive care alone in all prognostic groups. Finally, in previously treated patients with NSCLC, single-agent oral topotecan was shown to be noninferior in 1-year survival rate relative to the current standard of i.v. docetaxel. In future studies, oral topotecan will represent a good candidate for combination therapy with other i.v. or oral chemotherapy agents, monoclonal antibodies, and small molecule tyrosine kinase inhibitors.