title: Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.
abstract: OBJECTIVE
  In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m2 ombrabulin with 75 mg/m2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors.
  
  
  METHODS
  This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m2 combined with cisplatin 75 mg/m2. The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities.
  
  
  RESULTS
  Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m2 with cisplatin 75 mg/m2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients.
  
  
  CONCLUSIONS
  Ombrabulin 25 mg/m2 with cisplatin 75 mg/m2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients.
authors: Department of Medical Oncology, Cancer Chemotherapy Center and Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors: Shunji
authors: S
authors: Takahashi
authors: Department of Medical Oncology, Cancer Chemotherapy Center and Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors: Kenji
authors: K
authors: Nakano
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.|Present address: Shizuoka Cancer Center, Japan.
authors: Tomoya
authors: T
authors: Yokota
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.|Present address: National Cancer Center Hospital East, Japan.
authors: Kohei
authors: K
authors: Shitara
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors: Kei
authors: K
authors: Muro
authors: Sanofi K.K., Tokyo, Japan.
authors: Yoshinori
authors: Y
authors: Sunaga
authors: Sanofi K.K., Tokyo, Japan.
authors: Evelyne
authors: E
authors: Ecstein-Fraisse
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors: Takashi
authors: T
authors: Ura
keywords: Japanese patients; Phase 1 trial; cisplatin; ombrabulin; vascular disrupting agent