A phase I study of S-1 combined with weekly cisplatin for metastatic gastric cancer in an outpatient setting

A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer

“…Administration of split-or low-dose cisplatin has been suggested to enhance the clinical efficacy of treatment, resulting in mild to moderate toxicities when added to S-1 for patients with advanced gastric cancer [11][12][13][14][15]. However, in the present study, OS in the SWP arm tended to be inferior to that in the SP arm.…”

“…In this multicenter, randomized study, the standard daily dose of S-1 was used in both the SWP and SP arms to avoid confusion and error. This dose of S-1 corresponded to nearly the dose of 80 mg/m 2 /day and was slightly higher than that (70 mg/m 2 ) used in our previous phase I study [15]. If the dose of S-1 in the SWP arm had been 70 mg/ m 2 , drug omission and treatment delay may have been avoided to some extent.…”

“…A moderate to high dose of cisplatin is usually administered every 3-5 weeks to patients with advanced gastric cancer [4][5][6][7][8][9][10]; however, excessive hydration is vital to prevent renal toxicity at this dose. To reduce the necessity for excessive hydration and decrease renal toxicity, split-or low-dose cisplatin combined with S-1 has been investigated in several phase I and II studies [11][12][13][14][15] using various doses and schedules (S-1 administered at 80 mg/m 2 for 14-28 days and cisplatin infused at 10 mg/m 2 /day twice a week [11], 25 mg/m 2 /day once a week [12,13], or 4 mg/m 2 /day for 5 consecutive days/week [14]). In a phase I study, we determined the optimal split-dose of cisplatin when combined with S-1 at 70 mg/m 2 /day for 14 days every 3 weeks to be 20 mg/m 2 on days 1 and 8 [15].…”

“…To reduce the necessity for excessive hydration and decrease renal toxicity, split-or low-dose cisplatin combined with S-1 has been investigated in several phase I and II studies [11][12][13][14][15] using various doses and schedules (S-1 administered at 80 mg/m 2 for 14-28 days and cisplatin infused at 10 mg/m 2 /day twice a week [11], 25 mg/m 2 /day once a week [12,13], or 4 mg/m 2 /day for 5 consecutive days/week [14]). In a phase I study, we determined the optimal split-dose of cisplatin when combined with S-1 at 70 mg/m 2 /day for 14 days every 3 weeks to be 20 mg/m 2 on days 1 and 8 [15]. In that study, no adverse nonhematological events of grade 3 or more and no renal toxicity of grade 2 or more without forced hydration occurred in the majority of patients.…”

Phase I study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer

“…For combination chemotherapy regimens, which included S-1, either a 2-week administration with a 1-week interval protocol (Hyodo et al, 2003;Yoshida et al, 2006), or 3-week administration with a 1-to 2-week interval protocol have been reported (Koizumi et al, 2003;Ajani et al, 2005b). However, a recent post-marketing surveillance of S-1 disclosed that most toxicities increased during S-1/docetaxel/CDDP in metastatic gastric cancer T Takayama et al the third week of S-1 administration, often resulting in discontinuation of treatment (Nagashima et al, 2005).…”