A phase I study of sorafenib in combination with S-1 plus cisplatin in patients with advanced gastric cancer

作者：Yamada Yasuhide^*; Kiyota Naomi; Fuse Nozomu; Kato Ken; Minami Hironobu; Hashizume Kensei; Kuroki Yoshihiro; Ito Yuichiro; Ohtsu Atsushi

来源：Gastric Cancer, 2014, 17(1): 161-172.

DOI：10.1007/s10120-013-0247-9

• Sorafenib
• Phase I
• S-1
• Cisplatin
• Gastric adenocarcinoma

Sorafenib inhibits several receptor tyrosine kinases involved in tumor progression and angiogenesis. S-1, an oral fluorouracil antitumor drug, plus cisplatin (CDDP) is the standard regimen for advanced gastric adenocarcinoma (AGC) in Japan. The purpose of this phase I study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of sorafenib in combination with S-1 plus CDDP.
Patients with histologically confirmed previously untreated AGC were evaluated for eligibility and treated with sorafenib (400 mg bid, days 1-35), S-1 (40 mg/m(2) bid, days 1-21), and CDDP (60 mg/m(2), day 8). Treatment was continued until disease progression or unacceptable toxicity. Pharmacokinetics for sorafenib, 5-FU, and CDDP were investigated in cycle 1.
Thirteen patients were enrolled and received at least one dose of the study treatment. No specific or serious adverse event was newly reported in this study. Five patients had partial response and 8 had stable disease as the best response. Pharmacokinetic analysis showed no significant differences in the exposures of sorafenib when administered alone or in combination with S-1 and CDDP.
The present phase I study demonstrates the acceptable toxicity and preliminary efficacy of combined treatment with S-1, CDDP, and sorafenib.

• 出版日期2014-1