title: Topotecan and etoposide as first-line therapy for extensive disease small cell lung cancer: a phase II trial of a platinum-free regimen.
abstract: In the treatment of extensive disease of small cell lung cancer (ED SCLC) there is an urgent need for more effective and better-tolerated drug regimens. We report on a prospective phase II trial performed to evaluate the efficacy and safety of a platinum-free regimen--containing topotecan and etoposide--in the first-line treatment of ED SCLC. Between December 1999 and July 2001, 28 chemotherapy-naive patients with ED SCLC were recruited; 9 patients had stage IIIB disease and 19 patients had stage IV disease. Based on phase I results, patients received treatment with intravenous topotecan 1 mg/m2 (days 1-5) followed by intravenous etoposide 75 mg/m2 (days 8-10). Treatment courses were repeated every 28 days for a maximum of 6 cycles. A confirmed response rate of 46.4% with 1 complete response (CR) and 12 partial responses (PR) (95% CI=27.5-66.1%) was observed. Stable disease (SD) was observed in 18% of patients. The median time to response was 7.9 weeks (range: 7.7-15.1 weeks) and median survival was 29.9 weeks (range from 3.3 to 91.4 weeks). Main toxicities encountered were haematological with Grade III/IV neutropenia in 2.6/1.5% of courses and Grade III/IV thrombocytopenia in 1.8%/0.7% of courses. These toxicities were manageable and were not associated with clinical sequels. Non-haematological toxicities were generally mild with no Grade III/IV toxicities reported apart from Grade III alopecia. The combination therapy of topotecan and etoposide is active in first-line chemotherapy for patients with ED SCLC. The regimen showed a tolerable safety profile. Since drug scheduling plays a critical role in the combination of topoisomerase I and II inhibitors, concurrent administration of topotecan and etoposide might increase the efficacy.
authors.affiliation: Department of Thoracic Oncology, Hospital Grosshansdorf, Wöhrendamm 80, 22927 Grosshansdorf, Germany. dr.martin.reck@web.de
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Gesine
authors.initials: G
authors.lastname: Groth
authors.forename: Erika
authors.initials: E
authors.lastname: Buchholz
authors.forename: Elif
authors.initials: E
authors.lastname: Goetz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gatzemeier
authors.forename: Christian
authors.initials: C
authors.lastname: Manegold
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D019772:Topotecan