Phase I Study of Oral S-1 Plus Cisplatin With Concurrent Radiotherapy for Locally Advanced Non–Small-Cell Lung Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 75; no. 1; pp. 109 - 114
• Main Authors: Kaira, Kyoichi, M.D., Ph.D, Sunaga, Noriaki, M.D., Ph.D, Yanagitani, Noriko, M.D., Ph.D, Kawata, Tadayoshi, M.D., Ph.D, Utsugi, Mitsuyoshi, M.D., Ph.D, Shimizu, Kimihiro, M.D., Ph.D, Ebara, Takeshi, M.D., Ph.D, Kawamura, Hidemasa, M.D, Nonaka, Tetsuo, M.D., Ph.D, Ishikawa, Hitoshi, M.D., Ph.D, Sakurai, Hideyuki, M.D., Ph.D, Suga, Tatsuo, M.D., Ph.D, Hara, Kenichiro, M.D, Hisada, Takeshi, M.D., Ph.D, Ishizuka, Tamotsu, M.D., Ph.D, Nakano, Takashi, M.D., Ph.D, Mori, Masatomo, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2009
• Subjects: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Chemoradiotherapy; CHEMOTHERAPY; Cisplatin; Cisplatin - administration & dosage; Cisplatin - adverse effects; Combined Modality Therapy; COMBINED THERAPY; Concurrent; Dose Fractionation; DOSES; Drug Administration Schedule; Drug Combinations; DRUGS; Female; FEVER; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - radiotherapy; LUNGS; Male; Maximum Tolerated Dose; Middle Aged; NEOPLASMS; Non–small-cell lung cancer; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; PATIENTS; Phase I study; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; S-1; Tegafur - administration & dosage; Tegafur - adverse effects; TOXICITY; Phase I study; Non–small-cell lung cancer; Chemoradiotherapy; S-1; Concurrent; Cisplatin
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2008.06.1938

Purpose To determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable Stage III non–small-cell lung cancer (NSCLC). Methods and Materials S-1 was administered orally twice daily for 14 days and cisplatin on Days 1 and 8 of each cycle; this was repeated every 3 weeks. Doses of each drug were planned as follows: level 0, 50/40; level 1, 60/40; level 2, 70/40; level 3, 80/40 (S-1 [mg/m−2 /day−1 ]/cisplatin [mg/m−2 /day−1 ]). Thoracic radiation therapy was administered in 2 Gy fractions five times weekly to a total dose of 60 Gy. Results Ten patients were enrolled in this study. All patients received 60 Gy of thoracic radiotherapy and 7 (70%) patients received four cycles of chemotherapy. At level 1, 2 of 3 patients experienced a delay exceeding 10 days in the cisplatin administration of Day 29. Grade 4 neutropenia and Grade 3 fever occurred in 1 and 1 patients, respectively. Nonhematologic toxicities were mild. None developed ≥Grade 3 esophagitis or lung toxicity. At level 0, 2 of 7 patients developed dose-limiting toxicity. Thus, level 1 was considered the MTD and Level 0 was selected as the RD. Objective responses were seen in all patients. Conclusions The RD is the level 0 dose, and this regimen is a feasible and well-tolerated regimen for the treatment of patients with Stage III NSCLC.