105 Background: Capecitabine plus cisplatin (XP) is a standard global regimen for first-line treatment of advanced gastric cancer, however its efficacy compared to S-1 plus cisplatin (SP), a standard treatment in Japan has not been reported. To evaluate the efficacy of XP treatment, we conducted a multicenter randomized phase II trial comparing XP with SP for patients with advanced gastric cancer (ClinicalTrials.gov Identifier NCT0140624). Methods: Patients with unresectable metastatic or recurrent gastric cancer, 20–74 years of age and HER2-negative, were assigned to receive either S-1 40 mg/m2 bid for 21 days plus cisplatin 60 mg/m2 (day 8) every 5-week cycle or capecitabine 1000 mg/m2 bid for 14 days plus cisplatin 80 mg/m2 (day 1) every 3-week cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), time to treatment failure, overall response rate (ORR) and safety. Planned sample size was 100 (50 in each arm) according to PFS at 24-weeks. Immunohistochemical evaluation of biomarkers was also implemented. Results: From November 2011 to June 2013, 116 patients were randomized: median age, 65 years; 79 (68%) male; 63 intestinal and 53 diffuse cancer subtypes. In 109 eligible patients, 24-week %PFS was higher in both groups than the protocol-specified threshold of 40%. Median PFS for SP vs. XP was 25 weeks vs. 23 weeks (HR, 0.76; 95%CI, 0.5-1.16; p=0.203); OS was 58 weeks vs. 56 weeks (HR, 0.90; 95%CI, 0.52-1.57; p=0.712); and ORR was 27.5% vs. 32.7% (p=0.562), respectively. Sub-group analysis by histological classification showed that SP gave better PFS than XP in the diffuse type (HR, 0.42; 95%CI, 0.20-0.86; p=0.015) with no other statistical difference. Most common grade ≥3 adverse events with SP and XP were anemia (16%/ 19%), neutropenia (9%/17%), anorexia (18%/13%), diarrhea (11%/0%), nausea or vomiting (11%/15%), fatigue (5%/6%) and hyponatremia (7%/13%), respectively. Conclusions: XP and SP are comparable and can be recommended as 1st line treatments for advanced gastric cancer. Further analysis for biomarkers related to histology is warranted. Clinical trial information: NCT0140624.
A randomized phase II trial to elucidate the efficacy of capecitabine plus cisplatin (XP) and S-1 plus cisplatin (SP) as a first-line treatment for advanced gastric cancer: XP ascertainment vs. SP randomized PII trial (XParTS II)