Sadahiro Koinumaru

A phase II trial of oral UFT plus cisplatin (CDDP) in patients with non-small cell lung cancer (NSCLC)

Based on the results of our previous pilot study, we conducted a multi-institutional phase II study of combination chemotherapy consisting of oral UFT (Taiho Pharmaceutical Co. Ltd, Tokyo) plus cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). UFT capsule containing 100 mg tegafur and 224 mg uracil was orally administered in two divided doses on days 1 through 21 making the total tegafur dose 400 mg/m(2)/day (maximum 600 mg/body). CDDP was administered by drip infusion at a dose of 20 mg/m(2) on a 5-day schedule from day 8 to 12. Treatment was repeated every 4 weeks as long as the criteria for initiation of therapy were still met. Between April 1995 and March 1997, 51 patients were entered into the study. The mean age of all 50 eligible patients was 64 years(range: 40-78). There were 21 patients with clinical stage IIIB disease and 29 patients with IV disease. Thirty-two patients had adenocarcinoma, 14 had epidermoid carcinoma, and four had large cell carcinoma. Of the 47 assessable patients, 18 achieved a partial response with an overall response rate of 38.3% (95% confidence interval: 24.4-52.2%). The median response duration was 113 days. The median survival time of the eligible patients was 12.8 months, and the 1-year survival rate was 54%. Among the 51 patients enrolled, grade 3 or 4 leukopenia developed in one patient (2%), neutropenia in six patients (11. 8%), thrombocytopenia in six patients (11. 8%), and anemia in three patients (5. 9%). Non-hematological grade 3 or 4 toxicities included anorexia in 10 patients (19.6%), nausea in ten (19.6%), vomiting in two (3.9%), and diarrhea in two (3. 9%). Grade 3 abnormal laboratory data included bilirubinemia in four (7. 8%), GPT elevation in one (2.0%), and hematuria in one (2.0%). In conclusion, combination of CDDP plus oral UFT is efficacious, with low toxicity, in the treatment of advanced NSCLC. In particular, the low hematological toxicity may warrant application of this regimen to the treatment of elderly patients and in trials of concurrent chemoradiotherapy in patients with locally advanced NSCLC.

Pilot study of UFT combined with 5 consecutive days cisplatin in non-small cell lung cancer

Combined use of 5-fluorouracil (5-FU) and cisplatin has proven to have synergistic effects in many experimental systems and clinical studies. UFT, an oral preparation of uracil and tegafur in a 4:1 molar ratio, was reported to have enhanced activity as compared with 5-FU or tegafur alone against various human tumors. Based on those results, we conducted a pilot study to confirm the feasibility and antitumor effect of UFT in combination with cisplatin in patients with advanced non-small cell lung cancer (NSCLC). UFT was orally administered at a dose of 400 mg/m2 according to a protocol for step-wise prolongation of the administration period, such as days 1-14 in step I, days 1-21 in step II, days 1-28 in step III. During to course, cisplatin was administered at a fixed dose of 20 mg/m2/day on days 8 through 12. The course was repeated every 4 weeks. Numbers of patients enrolled in steps I, II, III were six, ten and six (a total of 22), respectively. There were three females and 19 males, PS scored 0/1/2 = 7/14/1, stage IIIA/IIIB/IV = 3/8/11. Adenocarcinoma/squamous cell carcinoma/large cell carcinoma = 11/7/4, and median age 68 (range 52-79). All 22 patients were evaluable for toxicity, and 21 for efficacy. Compliance of UFT declined as the administration period of UFT was prolonged. In step I, one patient had grade 3 toxicity of each neutropenia, thrombocytopenia, nausea/vomiting and diarrhea. In step II, grade 3, 4 neutropenia was seen in four patients, grade 3 thrombocytopenia and anorexia in one patient, and grade 3 nausea/vomiting in four patients. In step III, there was grade 3 neutropenia in two patients and grade 3 anorexia in one patient. All other toxicities were mild. The overall response rate was 38% (one CR and 7 PR, 95% C.I.: 21-59%). Combination therapy with oral UFT and 5-day infusion of cisplatin is feasible with substantial antitumor effect against advanced NSCLC. Since UFT compliance decreased in step III (no patient in step III received > 2 courses of treatment), we considered the step II schedule to be worth for further evaluation in a combination phase II study.

Phase II Study of Carboplatin Combined with Biweekly Docetaxel for Advanced Non-small Cell Lung Cancer

Background: The combination of carboplatin and docetaxel has been considered one of the standard treatments for advanced non-small cell lung cancer (NSCLC). To investigate a safer and more convenient schedule for outpatient, we conducted a phase II study to evaluate the efficacy and the safety of carboplatin plus biweekly docetaxel for advanced NSCLC. Patients and Methods: Patients with stage IIIB, IV, or postoperative recurrent NSCLC with good performance status were administered docetaxel at a dose of 35 mg/m2 on days 1 and 15 and carboplatin at an area under the curve (AUC) of 6 on day 1 every 4 weeks for at least three cycles. Results: Fifty patients were treated with median of three cycles (range 1–6). Grade 3/4 toxicities included neutropenia in 18 patients (36%), thrombocytopenia in 4 patients (8%), and anemia in 10 patients (20%). No patient experienced febrile neutropenia. Nonhematological toxicities were also mild to moderate, and there were no treatment-related deaths. The overall response rate was 30%, and the disease control rate was 70%. Among the elderly population, 54% of patients achieved partial response. Median progression-free survival was 4.8 months, and median overall survival was 11.8 months. Conclusions: Biweekly docetaxel plus carboplatin has a similar efficacy and lower toxicity compared with a standard triweekly regimen of docetaxel plus carboplatin, which is a suitable regimen for outpatients, including elderly patients.