A phase I study of S-1 with concurrent thoracic radiotherapy in elderly patients with localized advanced non-small cell lung cancer.
S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.
Takigawa
Nagio
N
Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. ntakigaw@md.okayama-u.ac.jp
Kiura
Katsuyuki
K
Hotta
Katsuyuki
K
Hosokawa
Shinobu
S
Nogami
Naoyuki
N
Aoe
Keisuke
K
Gemba
Kenichi
K
Fujiwara
Keiichi
K
Harita
Shingo
S
Takemoto
Mitsuhiro
M
Himei
Kengo
K
Shinkai
Tetsu
T
Fujiwara
Yoshirou
Y
Takata
Saburo
S
Tabata
Masahiro
M
Kanazawa
Susumu
S
Tanimoto
Mitsune
M
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid