A phase i dose escalation study of a pharmacobiologically based scheduling of capecitabine and mitomycin C in patients with gastrointestinal malignancies

Tanios Bekaii-Saab, Marisa Hill, Angela Campbell, Kavitha Kosuri, James Thomas, Miguel Villalona-Calero

Research output: Contribution to journalArticle

Abstract

Background: Mitomycin C (MMC) produces significant upregulation of thymidine phosphorylase, a principal determinant of the therapeutic index of capecitabine-based treatment, starting 4-6 days after treatment. On the basis of the time-dependency of this upregulation, we performed a phase I dose escalation study of capecitabine and MMC in patients with gastrointestinal malignancies. Methods: A total of 29 patients with advanced gastrointestinal malignancies received MMC at 6 mg/m2 on day 1 and capecitabine escalated in four successive patient cohorts of doses 500-1,000 mg/m 2/day twice daily on days 8-21, every 28 days. MMC was capped at 36 mg/m2. Results: A total of 29 patients were enrolled and 90% had at least one prior treatment in the metastatic setting. There was one DLT, grade 3 hand and foot syndrome, at dose level four. The most common toxicity was fatigue (61%). No patients experienced grade 4 toxicities. Nine patients experienced prolonged stability of disease. Conclusion: Capecitabine in combination with MMC in the proposed schedule is well-tolerated with evidence of preliminary activity. The recommended dose for phase II studies are MMC at 6 mg/m 2 on day 1 of a 28-day cycle with the dose capped at 36 mg/m 2, in combination with capecitabine at 1,000 mg/m2 twice daily on days 8-21.

Original languageEnglish (US)
Pages (from-to)863-869
Number of pages7
JournalCancer chemotherapy and pharmacology
Volume65
Issue number5
DOIs
StatePublished - Apr 2010

Keywords

  • Capecitabine
  • Gastrointestinal malignancies
  • Mitomycin C

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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