Phase II study of combination therapy with S-1 and irinotecan for advanced non-small cell lung cancer: west Japan thoracic oncology group 3505.
OBJECTIVE
To evaluate the efficacy and toxicity of combination therapy with the oral fluoropyrimidine formulation S-1 and irinotecan for patients with advanced NSCLC.


METHODS
Chemotherapy-naive patients with advanced NSCLC were treated with i.v. irinotecan (150 mg/m2) on day 1 and with oral S-1 (80 mg/m2) on days 1 to 14 every 3 weeks.


RESULTS
Fifty-six patients (median age, 63 years; range, 40-74 years) received a total of 286 treatment cycles (median, 5; range, 1-15). No complete responses and 16 partial responses were observed, giving an overall response rate of 28.6% [95% confidence interval (95% CI), 17.3-42.2%]. Twenty-four patients (42.9%) had stable disease and 12 patients (21.4%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 71.4% (95% CI, 57.8-82.7%). Median progression-free survival was 4.9 months (95% CI, 4.0-6.4 months), whereas median overall survival was 15 months. Hematologic toxicities of grade 3 or 4 included neutropenia (25%), thrombocytopenia (3.6%), and anemia (3.6%), with febrile neutropenia being observed in four patients (7.1%). The most common nonhematologic toxicities of grade 3 or 4 included anorexia (14.3%), fatigue (8.9%), and diarrhea (8.9%). There were no deaths attributed to treatment.


CONCLUSIONS
The combination of S-1 and irinotecan is a potential alternative option with a favorable toxicity profile for the treatment of advanced NSCLC. This nonplatinum regimen warrants further evaluation in randomized trials.
Okamoto
Isamu
I
Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan. chi-okamoto@dotd.med.kindai.ac.jp
Nishimura
Takashi
T
Miyazaki
Masaki
M
Yoshioka
Hiroshige
H
Kubo
Akihito
A
Takeda
Koji
K
Ebi
Noriyuki
N
Sugawara
Shunichi
S
Katakami
Nobuyuki
N
Fukuoka
Masahiro
M
Nakagawa
Kazuhiko
K
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin