Phase I and pharmacologic study of weekly bolus topotecan for advanced non-small-cell lung cancer.
OBJECTIVE
We conducted a phase I trial of the topoisomerase I inhibitor topotecan for the purpose of determining the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of topotecan when administered weekly to patients with advanced non-small-cell lung cancer.


METHODS
Twelve patients with stage IIIB or IV disease were treated with topotecan by 30-minute intravenous infusion on days 1, 8, and 15 every 4 weeks. The dose was escalated in 2-mg/m2 increments from the starting dose of 4 mg/m2 until the MTD was reached. After the MTD had been reached in previously treated patients, chemotherapy-naive patients were enrolled for treatment at that dose, and the dose was escalated to estimate the MTD in the treatment-naive group.


RESULTS
The MTD of topotecan was determined to be 6 mg/m2 in the previously treated group and 8 mg/m2 in the chemotherapy-naive group. All 3 previously treated patients experienced DLT at the 6-mg/m2 dose level. Although only 1 of the 3 previously treated patients experienced DLT (grade 4 neutropenia for > or = 3 days) at the 8-mg/m2 dose level, skipping the topotecan dose on day 15 because of neutropenia was reported in 2 patients. Anorexia and general fatigue were the common nonhematologic toxicities.


CONCLUSIONS
The recommended dose of topotecan for phase II studies in previously untreated patients is 6 mg/m2 on days 1, 8, and 15, every 28 days, and 4 mg/m2 appears to be a suitable dose for use in previously treated patients with this schedule.
Masuda
Noriyuki
N
Department of Respiratory Medicine, Kitasato University School of Medicine, Japan. masuda@med.kitasato-u.ac.jp
Matsui
Kaoru
K
Negoro
Shunichi
S
Takeda
Koji
K
Kudoh
Shinzoh
S
Nakagawa
Kazuhiko
K
Mukaiyama
Akihira
A
Arase
Hiroaki
H
Yoshida
Pascal
P
Ijima
Toshiyuki
T
Takada
Minoru
M
Fukuoka
Masahiro
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016879:Salvage Therapy; D015996:Survival Rate; D014018:Tissue Distribution; D019772:Topotecan / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019772:Topotecan