Phase I study of combination chemotherapy consisting of capecitabine plus fractional cisplatin for unresectable gastric cancer in an outpatient setting.

Abstract

173 Background: The combination chemotherapy of capecitabine and cisplatin is one of the standard regimen for unresectable gastric cancer. However, the high dose of cisplatin could cause the nephrotoxicity and require the adequate hydration to avoid the damage of renal during the administration. For that reason, the hospitalization is recommended for the patients to receive the chemotherapy including high dose of cisplatin. The present study aimed to establish the proper dose of fractional cisplatin in the combination with capecitabine in an outpatient setting. Methods: Capecitabine was administered orally every day from the evening of day 1 to the morning of 15. Cisplatin were infused on days 1, 8 and 15 for 60 minutes without hydration. The starting dose of cisplatin was 15 mg/m2 as level 1. The following cisplatin dose could be given to subsequent cohorts of patients depending on safety findings observed in the previous cohort: level 2, 20 mg/m2 and level 3, 25 mg/m2, respectively. Serum concentration of total platinum was analyzed before the administration of cisplatin on days 1, 8 and 15. Results: A total of 9 patients were recruited. The median age was 64 years and there were 8 males and one female. Histological types included intestinal (n=5) and diffuse (n=4). Eight patients had multiple metastatic sites, including lymph nodes (n=8), peritoneum (n=5), liver (n=3), lung (n=2) and bone (n=1). The major toxicities were thrombocytopenia (67%), leukopenia (56%) and neutropenia (22%). However, no dose-limiting toxicity was observed in each level. Therefore, the recommended dose of cisplatin was 25 mg/m2. Of the 9 patients, 6 patients had measurable lesions and 5 patients had partial responses, resulting in an overall response rate of 83%. The median administered course was four. In patients at level 3, the mean concentration of total platinum on days 8 and 15 were 0.25μg/ml and 0.42μg/ml, respectively. Conclusions: The recommend dose of cisplatin was confirmed with 25 mg/m2 weekly. Although its safety and feasibility should be evaluated in further clinical trial, this regimen could be expected as an outpatient treatment for unresectable gastric cancer. Clinical trial information: 000005708.