Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer

Background We evaluated the maximum tolerated dose (MTD) and safety of sunitinib plus capecitabine/cisplatin (XP) or capecitabine/oxaliplatin (XELOX) in Korean patients with advanced gastric cancer (GC). Methods Sunitinib (37.5 or 25 mg/day) was administered on a 2-week-on/1-week-off schedule with chemotherapy. Assessments included dose-limiting toxicity (DLT), safety, pharmacokinetics, and antitumor activity. Results Twenty-eight patients received sunitinib/XP; 48 received sunitinib/XELOX. The MTDs were: sunitinib 25 mg/day, cisplatin 80 mg/m², and capecitabine 1,000 mg/m²; sunitinib 37.5 mg/day, oxaliplatin 110 mg/m², and capecitabine 800 mg/m²; and sunitinib 25 mg/day, oxaliplatin 110 mg/m², and capecitabine 1,000 mg/m². DLTs at the MTDs comprised grade (G) 4 febrile neutropenia plus G3 diarrhea (n = 1; sunitinib/XP), dose delays due to hematologic toxicity (n = 2; both sunitinib/XP), G3 bleeding (menorrhagia; n = 1; sunitinib/XELOX), and G3 increased alanine aminotransferase levels (n = 1; sunitinib/XELOX). There was a high frequency of G3/4 hematologic adverse events observed with both treatment regimens, particularly with sunitinib/XP. Frequent non-hematologic, G3/4 adverse events were nausea, stomatitis, and hypophosphatemia with sunitinib/XP and hypophosphatemia and pulmonary embolism with sunitinib/XELOX. No drug–drug interactions were apparent. At the MTDs, median progression-free survival was 6.4 months and 5.5–8.0 months for sunitinib/XP and sunitinib/XELOX, respectively; and the objective response rate was 46.7 % and 43.5–45.5 % for sunitinib/XP and sunitinib/XELOX, respectively. Conclusions At the MTD, sunitinib/XELOX had an acceptable safety profile in patients with advanced GC.