A phase I trial of a 5-day schedule of intravenous topotecan and etoposide in previously untreated patients with small-cell lung cancer.
A phase I dose-escalation study was undertaken to determine the maximum tolerated dose of the intravenous combination of topotecan and etoposide in previously untreated patients with small-cell lung cancer. Nineteen patients were treated with 30-min infusions of topotecan (0.5 mg/m(2)/day for cohort 1; 0.75 mg/m(2)/day for cohort 2) followed by 1-hour infusions of a fixed daily dose of etoposide (60 mg/m(2)/day) for 5 consecutive days every 3 weeks. Patient cohort 1 (n = 7) received a total of 41 courses of chemotherapy. Grade 4 neutropenia occurred after 17% of the courses of therapy, and there was 1 episode of dose-limiting toxicity in this patient cohort. In patient cohort 2 (n = 12), a total of 64 courses of chemotherapy were administered. Grade 3 or 4 neutropenia occurred following 41 and 37% of the courses of therapy, respectively. Grade 3 thrombocytopenia occurred following 19% of the courses of therapy, and there were 3 episodes of dose-limiting toxicity in this patient cohort. There were no toxic deaths, and all nonhematologic toxicity (except hair loss) was </= grade 2. No further dose escalation was performed because of the degree of myelosuppression seen in patient cohort 2. All 19 patients were evaluable for response. Eighteen (95%) patients responded (14 partial responses and 4 complete responses) and the median survival was 10 months. This 5-day schedule of intravenous topotecan and etoposide administered sequentially on the same day is well tolerated, and the preliminary response rates were high in patients with previously untreated small-cell lung cancer.
O'Neill
P
P
Department of Medical Oncology, Clatterbridge Centre of Oncology, Bebington, Wirral, Merseyside, UK.
Clark
P I
PI
Smith
D
D
Marshall
E
E
Hannigan
K
K
Ross
G
G
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
D005047:Etoposide; D019772:Topotecan