A phase I, dose-finding study of sunitinib combined with cisplatin and 5-fluorouracil in patients with advanced gastric cancer
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Background This phase I, open-label, dose-escalation study examined the safety, maximum tolerated dose (MTD), and pharmacokinetics of sunitinib plus chemotherapy in patients with advanced gastric cancer. Patients and methods Sunitinib (25 or 37.5 mg/day, Schedule 2/1: 2 weeks on treatment/1 week off) plus chemotherapy (fixed starting doses of cisplatin 80 mg/m2 and 5-fluorouracil [5-FU] 4,000 mg/m2) was administered to patients with advanced gastric cancer who had not received prior therapy for metastatic disease. Results Thirty-four patients were enrolled and received sunitinib 25 mg/day (n = 24) or 37.5 mg/day (n = 10) plus chemotherapy. No dose-limiting toxicity (DLT) was reported in the sunitinib 37.5 mg cohort. However, repeated patterns of myelosuppression beyond the first cycle led to investigation of sunitinib 25 mg/day. This was the MTD, and one DLT (grade 3 mucosal inflammation) was reported. The combination had an acceptable adverse event profile; generally of grade 1/2. There was no evidence of a pharmacokinetic drug–drug interaction between sunitinib and 5-FU. Six patients (26 %) receiving the MTD had a partial response and eight patients experienced stable disease ≥3 months. Conclusions Sunitinib plus cisplatin 80 mg/m2 and 5-FU 4,000 mg/m2 were combinable and adverse events were manageable. The MTD of sunitinib was established as 25 mg/day on Schedule 2/1.
Keywords5-fluorouracil Advanced gastric cancer Cisplatin Sunitinib
We thank the participating patients and their families, as well as the network of investigators, research nurses, study coordinators, and operations staff. Medical writing support was provided by Nicola Crofts at ACUMED® (Tytherington, UK) and was funded by Pfizer Inc.
This study was sponsored by Pfizer Inc. Drs Bellmunt and Montagut received funding from a Fondo de Investigaciones Sanitarias (FIS) grant: ISCIII/FEDER(RD06/0020/0109
Conflicts of interest
Reza Khosravan, Maria-Jose Lechuga, Xun Lin, and Jennifer Tursi are Pfizer Inc. employees and hold Pfizer stock.
Marta Puig is a Pfizer Inc. employee.
Carlos Gómez-Martín, Ramon Salazar, Clara Montagut, Marta Gil-Martín, Juan Núñez, and Joaquim Bellmunt have no conflicts of interest to disclose.
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