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Phase II Comparator Study of Oral Versus Intravenous Topotecan in Patients With Chemosensitive Small-Cell Lung Cancer

From the Asklepios Fachklinik, Gauting bei München, Munich; Krankenhaus Grosshansdorf, Grosshansdorf; West German Cancer Centre, Essen; Hospital of Diseases of Respiratory Organs, Ebensfield, Germany; Hôpital Arnaud de Villeneuve, Montpellier; Centre Hospitalier Universitaire Hôpital Lyautey, Strasbourg; Centre François Baclesse, Caen, France; Christie Hospital, Manchester; SmithKline Beecham Pharmaceuticals, Harlow, United Kingdom; Monash Medical Centre, Clayton, Australia; and SmithKline Beecham Pharmaceuticals, Collegeville, PA.

Address reprint requests to Joachim von Pawel, MD, Asklepios Fachklinik, Robert-Koch Allee 2, 82131, Gauting bei München, Germany.

PURPOSE: Topotecan, administered intravenously, is active in small-cell lung cancer (SCLC). In this study, the comparability of oral topotecan to IV topotecan was investigated.

PATIENTS AND METHODS: Patients with SCLC that had relapsed 90 days or more after cessation of initial chemotherapy were randomized to receive either oral topotecan (Hycamtin) 2.3 mg/m²/d x 5 (52 patients) or IV topotecan 1.5 mg/m²/d x 5 (54 patients), every 21 days.

RESULTS: Response rates in this phase II randomized study were 23% (12/52) in the oral topotecan arm and 15% (8/54) in the IV topotecan arm. All radiological responses were confirmed by an independent radiologist. Median survival was 32 weeks (oral) and 25 weeks (IV). Good symptom control, defined as sustained improvement or no deterioration, was evident in both treatment groups. Topotecan was generally well tolerated, with myelosuppression being the major toxicity. Grade 4 neutropenia occurred in 35.3% of patients on oral topotecan and in 67.3% of patients on IV topotecan, which was statistically significant (P = .001). Fever/infection more than or equal to grade 2 associated with grade 4 neutropenia, together with sepsis, occurred in only 5.1% of courses (oral) and 3.3% of courses (IV). Non-hematological toxicity consisted mainly of vomiting (oral: 36.5% of patients; IV: 31.5% of patients) and nausea (oral: 26.9% of patients; IV: 40.7% of patients).

CONCLUSION: This study found oral topotecan to be similar in efficacy to IV topotecan in the treatment of patients with relapsed SCLC, sensitive to first-line chemotherapy, with less grade 4 neutropenia and greater convenience of administration.

I.C., S.L., and G.R. are employees of SmithKline Beecham.

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