title: Response to topotecan of symptomatic brain metastases of small-cell lung cancer also after whole-brain irradiation. a multicentre phase II study.
abstract: The purpose of this multicentre phase II study was to evaluate the efficacy and toxicity of topotecan in pretreated patients with small-cell lung cancer (SCLC) who relapsed with symptomatic brain metastases. 30 patients with a median age of 62 years were entered into the study. 22 patients received the initially planned dose of 1.5 mg/m(2) topotecan as a 30-min intravenous (i.v.) infusion for 5 consecutive days every 3 weeks. Due to the observed thrombocytopenia, the dose was reduced to 1.25 mg/m(2) in the last 8 patients. All 30 patients were pretreated with chemotherapy: 14 with one and 16 with at least two protocols. 8 patients had prior whole-brain iradiation (WBI): 7 in the prophylactic and 1 in the palliative setting. Concomitant systemic metastases were recorded in 24 patients at the time of brain relapse. Cerebral metastases responded in 33% of patients (10/30; three complete responses (CR) and seven partial responses (PR)). Noteworthy is the fact that response was achieved in 4 of 8 patients pretreated by WBI (3 in prophylactic and 1 in palliative setting). The systemic response rate was 29% (7/24). Median time to progression was 3.1 months (range 0.25-14.2+ months), median survival from the beginning of this study was 3.6 months (range 0.25-14.2+ months). Therapy was generally well tolerated, with myelotoxicity being the most common adverse event. Grade 3 leucocytopenia according to the Common Toxicity Criteria (CTC) occurred in 28% (23/83) of the courses and grade 4 in 22% (18/83). Grade 3 thrombocytopenia was observed in 17% of the courses (14/83) and grade 4 in 11% (9/83). 17% of patients (5/30) had a documented grade 3 infection. These results using topotecan are promising in heavily pretreated patients with SCLC brain metastases and merit further evaluation.
authors.affiliation: Department of Hematology, Oncology and Transfusion Medicine, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. akorfel@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Korfel
authors.forename: C
authors.initials: C
authors.lastname: Oehm
authors.forename: J
authors.initials: J
authors.lastname: von Pawel
authors.forename: Uwe
authors.initials: U
authors.lastname: Keppler
authors.forename: M
authors.initials: M
authors.lastname: Deppermann
authors.forename: S
authors.initials: S
authors.lastname: Kaubitsch
authors.forename: E
authors.initials: E
authors.lastname: Thiel
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000556:secondary*; D016371:Cranial Irradiation; D018450:Disease Progression; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan