s-1-(combination) and Radiation-Pneumonitis

We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC).. Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30-40 mg/m2 two times daily) on Days 1-14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate.. Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6-71.4%), and the median PFS was 16.8 months (95% CI 7.8-not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3-4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed.. Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Paclitaxel; Progression-Free Survival; Radiation Pneumonitis; Tegafur; Treatment Outcome

To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer.. Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days).. Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%).. The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Radiation Pneumonitis; Tegafur; Treatment Outcome