Investigational New Drugs

, Volume 30, Issue 5, pp 1942–1949

Phase I combination study of trabectedin and capecitabine in patients with advanced malignancies

Authors

    • University of Colorado Cancer Center
  • E. Rivera
    • M. D. Anderson Cancer Center
  • M. Basche
    • University of Colorado Cancer Center
  • S. L. Moulder-Thompson
    • M. D. Anderson Cancer Center
  • J. Li
    • Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  • S. Eppers
    • University of Colorado Cancer Center
  • S. Grolnic
    • University of Colorado Cancer Center
  • C. O’Bryant
    • University of Colorado Cancer Center
  • D. Cleere
    • The Methodist Hospital
  • Y. A. Elsayed
    • Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  • S. G. Eckhardt
    • University of Colorado Cancer Center
PHASE I STUDIES

DOI: 10.1007/s10637-011-9747-9

Cite this article as:
Gore, L., Rivera, E., Basche, M. et al. Invest New Drugs (2012) 30: 1942. doi:10.1007/s10637-011-9747-9

Summary

Background To determine the maximum tolerated dose (MTD), safety and pharmacokinetics of trabectedin with capecitabine in patients with advanced malignancies. Design In this Phase I, open-label, dose-finding study, patients refractory to standard therapy received trabectedin (3-h intravenous infusion, 0.4–1.3 mg/m2, day 1) and capecitabine (2,000 or 1,600 mg/m2/day orally, days 2–15) every 3 weeks. Standard “3 + 3” dose escalation was used to define the MTD. Antitumor response was assessed every two cycles; adverse events (AEs) were recorded throughout. Results Forty patients received 149 cycles of treatment (median 2; range 1–11) at nine dose levels. Gastrointestinal dose-limiting toxicities in two patients at two dose levels with capecitabine at 2,000 mg/m2/day prompted dose reduction to 1,600 mg/m2/day and initiation of new trabectedin dose escalation at 0.6 mg/m2. The MTD was capecitabine 1,600 mg/m2/day + trabectedin 1.1 mg/m2. Common grade 3–4 drug-related AEs were neutropenia (20%), nausea (18%), diarrhea (15%) and palmar-plantar erythrodysesthesia (15%). One patient with cholangiocarcinoma achieved a sustained partial response, and 18 patients maintained stable disease (six for ≥6 months). Conclusions The combination of trabectedin and capecitabine is generally well tolerated, without pharmacokinetic interactions, and shows some activity in patients with advanced cancers.

Keywords

Advanced malignancyCapecitabinePharmacokineticsPhase ITrabectedin

Copyright information

© Springer Science+Business Media, LLC 2011