Faculty Collaboration Database

A phase I dose escalation study of a pharmacobiologically based scheduling of capecitabine and mitomycin C in patients with gastrointestinal malignancies. Cancer Chemother Pharmacol 2010 Apr;65(5):863-9

Date

08/07/2009

Pubmed ID

19657639

Pubmed Central ID

PMC4261191

DOI

10.1007/s00280-009-1091-9

Scopus ID

2-s2.0-77649185248 (requires institutional sign-in at Scopus site)

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/m2/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/m2 on day 1 of a 28-day cycle with the dose capped at 36 mg/m2, in combination with capecitabine at 1,000 mg/m2 twice daily on days 8-21.

Author List

Bekaii-Saab T, Hill M, Campbell A, Kosuri K, Thomas J, Villalona-Calero M

Author

James P. Thomas MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antineoplastic Combined Chemotherapy Protocols
Capecitabine
Deoxycytidine
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Fluorouracil
Gastrointestinal Neoplasms
Humans
Male
Middle Aged
Mitomycin