Phase I and pharmacologic study of docetaxel and irinotecan in advanced non-small-cell lung cancer.
OBJECTIVE
We conducted a phase I trial of docetaxel, a new antimicrotubule agent, combined with irinotecan (CPT-11), a topoisomerase I inhibitor. The aim was to determine the maximum-tolerated dose (MTD) of docetaxel combined with CPT-11, as well as the dose-limiting toxicities (DLTs) of this combination in advanced non-small-cell lung cancer (NSCLC) patients.


METHODS
Thirty-two patients with stage IIIB or IV NSCLC were treated at 4-week intervals with docetaxel (60 minutes, day 2) plus CPT-11 (90 minutes, days 1, 8, and 15). The starting doses of docetaxel/CPT-11 were 30/40 mg/m(2), and doses were escalated in 10-mg/m(2) increments until the MTD was reached.


RESULTS
The MTD of docetaxel/CPT-11 was 50/60 mg/m(2) (level 5A), or 60/50 mg/m(2) (level 5B). Neutropenia and diarrhea were the DLTs. CPT-11 did not affect the pharmacokinetics of docetaxel. There were 11 (37%) partial responses among 30 patients. The median survival time was 48 weeks, and the 1-year survival rate was 44.9%.


CONCLUSIONS
The combination of docetaxel and CPT-11 seems to be active against NSCLC, with acceptable toxicity. The recommended dose for phase II studies is 50 mg/m(2) of CPT-11 (days 1, 8, and 15) and 50 mg/m(2) of docetaxel (day 2) administered every 28 days.
Masuda
N
N
Departments of Internal Medicine, Osaka Prefectural Habikino Hospital and Kinki University School of Medicine, Osaka, Japan.
Negoro
S
S
Kudoh
S
S
Sugiura
T
T
Nakagawa
K
K
Saka
H
H
Takada
M
M
Niitani
H
H
Fukuoka
M
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008870:Microtubules / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin