Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer

Cancer Chemother Pharmacol. 2012 Feb;69(2):439-46. doi: 10.1007/s00280-011-1723-8. Epub 2011 Aug 19.

Abstract

Purpose: The primary objective of this Phase I study was to assess the safety and tolerability of the vascular endothelial growth factor signalling inhibitor cediranib in combination with cisplatin plus an oral fluoropyrimidine, in Japanese patients with previously untreated advanced gastric cancer.

Methods: Patients received continuous, once-daily oral doses of cediranib 20 mg in combination with either cisplatin (60 mg/m(2) iv day 1) plus S-1 (40-60 mg bid, days 1-21) every 5 weeks for a maximum of eight cycles [Arm A]; or cisplatin (80 mg/m(2) iv, day 1) plus capecitabine (1,000 mg/m(2) bid, days 1-14) every 3 weeks for a maximum of six cycles [Arm B]. In both arms, the assessment period for dose-limiting toxicities (DLTs) was the first 21 days of cycle 1.

Results: Fourteen patients (Arm A, n = 6; Arm B, n = 8) were enrolled and received at least one dose of cediranib. One patient in each arm experienced a DLT (Arm A; decreased appetite, grade 3; Arm B, decreased appetite, fatigue and hyponatraemia, all grade 3). Overall, the most common adverse events were decreased appetite, fatigue and nausea (all n = 13 [92.9%]). Preliminary efficacy evaluation showed one confirmed (Arm A) and three unconfirmed (Arm A, n = 1; Arm B, n = 2) partial responses that were ongoing at data cut-off.

Conclusions: Cediranib 20 mg/day in combination with cisplatin and S-1 or capecitabine was tolerable, with no new toxicities identified, and showed preliminary evidence of antitumour activity.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Appetite / drug effects
  • Area Under Curve
  • Asian People
  • Capecitabine
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / pharmacokinetics
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacokinetics
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / pharmacokinetics
  • Humans
  • Hyponatremia / chemically induced
  • Japan
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Neutropenia / chemically induced
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Oxonic Acid / pharmacokinetics
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / ethnology
  • Stomach Neoplasms / metabolism
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Tegafur / pharmacokinetics
  • Treatment Outcome
  • Tumor Burden / drug effects

Substances

  • Quinazolines
  • Deoxycytidine
  • Tegafur
  • Oxonic Acid
  • Capecitabine
  • cediranib
  • Cisplatin
  • Fluorouracil