Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced non-small cell lung cancer: Thoracic oncology research group study 0502.
A phase I/II trial of TS-1 combined with gemcitabine was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients older than 70 years of age received TS-1 orally b.i.d. on days 1-14 and gemcitabine intravenously on days 8 and 15 every 4 weeks. In phase I (n=22), each cohort received escalating doses of TS-1 (30-40 mg/m(2) b.i.d.) and gemcitabine (800-1000 mg/m(2)); MTD was 40 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine; RD was 30 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine. Dose-limiting toxicities included a grade 3 infection, skin toxicity, and stomatitis. In phase II (n=37), the overall response rate was 27% (90% confidence interval (CI): 15-42%) and the median time to progression and overall survival were 4.2 months (90% CI: 3.2-5.7) and 12.9 months (90% CI: 10.4-14.7), respectively. The most common grade 3 or higher toxicity was neutropenia (45.9%), and thrombocytopenia was observed in 13.5% of patients. Two cases each of grade 3 pneumonitis and skin toxicity were observed, but nonhematological toxicities occurred at generally low frequencies. TS-1 with gemcitabine is a promising doublet regimen in elderly patients with advanced NSCLC with acceptable toxicities.
Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan. tseto@nk-cc.go.jp
Takashi
T
Seto
Takeharu
T
Yamanaka
Izumi
I
Wasada
Nobuhiko
N
Seki
Hiroaki
H
Okamoto
Takashi
T
Ogura
Masahiko
M
Shibuya
Yuichi
Y
Takiguchi
Tetsu
T
Shinkai
Noriyuki
N
Masuda
Yukito
Y
Ichinose
Kenji
K
Eguchi
Koshiro
K
Watanabe
D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007239:Infections / Q000209:etiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D020714:Maximum Tolerated Dose; D009367:Neoplasm Staging; D017640:Silicates / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D014025:Titanium / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
D017640:Silicates; D003841:Deoxycytidine; C103828:titanium silicide; D014025:Titanium; D000093542:Gemcitabine