Irinotecan and cisplatin with concurrent split-course radiotherapy in locally advanced nonsmall-cell lung cancer: a multiinstitutional phase 2 study.
BACKGROUND
The purpose was to determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split-course thoracic radiotherapy (TRT) in locally advanced nonsmall-cell lung cancer.


METHODS
Fifty patients fulfilling the following eligibility criteria were enrolled: chemotherapy-naive, good performance status (PS, 0-2), age <75, stage III, and adequate organ function. The patients received irinotecan 60 mg/m(2) intravenously on Days 1, 8, and 15, and cisplatin 80 mg/m(2) intravenously on Day 1 in the first group. The doses were reduced to 50 and 60 mg/m(2), respectively, in the second group. Two cycles of chemotherapy were repeated every 4 weeks. Split-course thoracic radiotherapy of 2 Gy/day commenced on Day 2 of each chemotherapy cycle, with 28 and 32 Gy administered in the first and second cycles, respectively.


RESULTS
Fifty patients were eligible and 48 (16 in the first, 32 in the second group) patients were assessable for response, toxicity, and survival. The overall response was 83% (95% confidence interval [CI], 70%-93%). Grade 4 leukopenia, neutropenia, grade 3 or 4 diarrhea, pneumonitis, esophagitis, and fatigue occurred in 21%, 48%, 19%, 10%, and 19%, respectively. The median time to progression was 8.2 months. The median overall survival time and the 2- and 5-year survival rates were 20.1 months, 47.1%, and 17.1%, respectively. In subgroup analysis, grade 4 neutropenia, grade 3 or 4 diarrhea, the overall response, and the median survival times of the first/second groups were 63%/41%, 19%/19%, 75%/88%, and 13.1/33.4 months, respectively.


CONCLUSIONS
This combined modality of irinotecan and cisplatin with concurrent TRT is active and further investigations are warranted at the second group dose level.
Fukuda
Minoru
M
Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan. mifukuda258@nifty.com
Soda
Hiroshi
H
Fukuda
Masaaki
M
Kinoshita
Akitoshi
A
Nakamura
Yoichi
Y
Nagashima
Seiji
S
Takatani
Hiroshi
H
Tsukamoto
Kazuhiro
K
Kohno
Shigeru
S
Oka
Mikio
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome
D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin