title: Phase I study of irinotecan and cisplatin with concurrent split-course radiotherapy in limited-disease small-cell lung cancer.
abstract: We conducted a phase I study of irinotecan (CPT-11) and cisplatin with concurrent split-course radiotherapy in limited-disease small-cell lung cancer (LD-SCLC). This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy. Four chemotherapy cycles of CPT-11 (days 1, 8 and 15) and cisplatin (day 1) were repeated every 28 days. Radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle with 20 Gy administered from the first to the third cycles (a total of 60 Gy). 17 patients were enrolled at three dose levels (CPT-11/cisplatin: 40/60, 50/60 and 60/60 mg/m(2)), and 16 were evaluable for toxicity and outcome. 2 of 4 patients at 60/60 mg/m(2) refused continuation of therapy because of general fatigue, and the relative dose intensity of CPT-11 at 50/60 mg/m(2) was approximately 50%. These levels were considered as the MTD. Tumour responses included four complete responses (CR), 11 partial responses (PR) and one no change (NC), and the overall response rate was 93.8% (95% confidence interval: (CI) 71.7-98.9%). This combined modality is tolerable, and CPT-11/cisplatin of 40/60 mg/m(2) in this modality is recommended for phase II study.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Japan. okamikio@net.nagasaki-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Kuba
authors.forename: M
authors.initials: M
authors.lastname: Ichiki
authors.forename: T
authors.initials: T
authors.lastname: Rikimaru
authors.forename: H
authors.initials: H
authors.lastname: Soda
authors.forename: J
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
authors.forename: K
authors.initials: K
authors.lastname: Nakatomi
authors.forename: F
authors.initials: F
authors.lastname: Narasaki
authors.forename: S
authors.initials: S
authors.lastname: Nagashima
authors.forename: H
authors.initials: H
authors.lastname: Takatani
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: A
authors.initials: A
authors.lastname: Kinoshita
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin