A dose escalating study of topotecan preceding cisplatin in previously untreated patients with small-cell lung cancer.
BACKGROUND
The aim was to define the MTD of topotecan (TPT) given before cisplatin in patients with previously untreated SCLC.


METHODS
Alternating cycles A and B to a total of 6 cycles were given. Cycle A: TPT days 1-5 and cisplatin (50 mg/m2) day 5. Cycle B consisted of teniposide, carboplatin, vincristine, and cisplatin. TPT was escalated at doses 0.75, 1.0, 1.25, and 1.5 mg/m2. DLT was defined for the first cycle as grade 4 neutropenia with fever or when lasting > 7 days, or grade 4 thrombocytopenia.


RESULTS
Fifteen patients with limited disease and six patients with extensive disease were included. No episodes of DLT were recorded in the first cycles A and consequently 1.5 mg/m2 was defined as MTD. At 1.5 mg/m2 (11 patients, 30 cycles), four and three episodes of grade 4 thrombocytopenia and neutropenia lasting more than seven days occurred in subsequent cycles A. Thrombocytopenia and anaemia were cumulative as more cycles were administrated. Non-hematological toxicity was mild. The response rate was 86% (95% confidence interval (95% CI): 64%-97%) with 33% (95% CI: 15%-57%) achieving CR.


CONCLUSIONS
1.5 mg/m2 TPT can be delivered safely with 50 mg/m2 cisplatin on day 5 in patients with previously untreated SCLC.
Sorensen
M
M
The Finsen Centre, Rigshospitalet, Copenhagen, Denmark. msorensen@dadlnet.dk
Jensen
P B
PB
Herrstedt
J
J
Hirsch
F R
FR
Hansen
H H
HH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
D019772:Topotecan; D002945:Cisplatin