当前位置： SCI文献检索 > INVESTIGATIONAL NEW DRUGS期刊下所有文献 > Phase I study of sunitinib plus S-1 and cisplatin in Japanese patients with advanced or metastatic gastric cancer.

Phase I study of sunitinib plus S-1 and cisplatin in Japanese patients with advanced or metastatic gastric cancer.

Abstract：

BACKGROUND:This phase I, dose-finding study evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib plus S-1/cisplatin in Japanese patients with advanced/metastatic gastric cancer. PATIENTS AND METHODS:Patients received oral sunitinib on a continuous daily dosing (CDD) or 2-weeks-on/2-weeks-off schedule (Schedule 2/2; 25 mg/day or 37.5 mg/day), plus S-1 (80-120 mg/day)/cisplatin 60 mg/m(2). RESULTS:Twenty-seven patients received treatment, including 26 patients treated per protocol (sunitinib 25 mg/day CDD schedule, n = 4; sunitinib 25 mg/day Schedule 2/2, n = 16 [dose-limiting toxicity (DLT) cohort, n = 6 plus expansion cohort, n = 10]; sunitinib 37.5 mg/day Schedule 2/2, n = 6). One patient erroneously self-administered sunitinib 12.5 mg/day and was excluded from the analyses. The MTD was sunitinib 25 mg/day on Schedule 2/2. DLTs were reported for: 2/4 patients given sunitinib 25 mg/day on the CDD schedule; 1/6 patients administered sunitinib 25 mg/day on Schedule 2/2 (grade [G] 3 neutropenic infection, G4 thrombocytopenia, and S-1 dose interruption ≥5 days), and 3/6 patients given sunitinib 37.5 mg/day on Schedule 2/2. Results below are for the overall MTD cohort (n = 16). The most frequently reported G3/4 adverse events were neutropenia (93.8 %) and leukopenia (75.0 %). The objective response rate was 37.5 %; six additional patients experienced no disease progression for ≥24 weeks. Median progression-free survival was 12.5 months. No pharmacokinetic drug-drug interactions were observed between sunitinib/S-1/cisplatin and S-1/cisplatin. CONCLUSIONS:The MTD of sunitinib was 25 mg/day on Schedule 2/2 combined with cisplatin/S-1 in patients with advanced/metastatic gastric cancer. This regimen had a manageable safety profile and preliminary antitumor activity.

journal_name

Invest New Drugs

journal_title

Investigational new drugs

authors

Boku N,Muro K,Machida N,Hashigaki S,Kimura N,Suzuki M,Lechuga M,Miyata Y

doi

10.1007/s10637-013-9948-5

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

261-70

issue

eissn

0167-6997

issn

1573-0646

journal_volume

pub_type

杂志文章

在线工具

Phase I study of sunitinib plus S-1 and cisplatin in Japanese patients with advanced or metastatic gastric cancer.