Investigational New Drugs

, Volume 30, Issue 5, pp 1942–1949

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

  • Lia Gore
  • E. Rivera
  • M. Basche
  • S. L. Moulder-Thompson
  • J. Li
  • S. Eppers
  • S. Grolnic
  • C. O’Bryant
  • D. Cleere
  • Y. A. Elsayed
  • S. G. Eckhardt
PHASE I STUDIES

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 malignancy Capecitabine Pharmacokinetics Phase I Trabectedin 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Lia Gore
    • 1
  • E. Rivera
    • 2
  • M. Basche
    • 1
  • S. L. Moulder-Thompson
    • 2
  • J. Li
    • 3
  • S. Eppers
    • 1
  • S. Grolnic
    • 1
  • C. O’Bryant
    • 1
  • D. Cleere
    • 4
  • Y. A. Elsayed
    • 3
  • S. G. Eckhardt
    • 1
  1. 1.University of Colorado Cancer CenterAuroraUSA
  2. 2.M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Johnson & Johnson Pharmaceutical Research & Development, L.L.C.RaritanUSA
  4. 4.The Methodist HospitalHoustonUSA

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