Thymidine phosphorylase expression is associated with time to progression in patients receiving low-dose, docetaxel-modulated capecitabine for metastatic breast cancer

Fabio Puglisi, G. G. Cardellino, D. Crivellari, C. Di Loreto, M. D. Magri, A. M. Minisini, M. Mansutti, C. Andreetta, S. Russo, D. Lombardi, T. Perin, G. Damante, A. Veronesi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Preclinical data have indicated a synergistic interaction between docetaxel and capecitabine by means of taxane-induced up-regulation of thymidine phosphorylase (TP). On the basis of such premises, we conducted a phase II trial to determine the activity and tolerability of weekly docetaxel plus capecitabine in patients with metastatic breast cancer (MBC). Furthermore, we explored the relationship between TP tumor expression and benefit from this regimen. Patients and methods: Patients received docetaxel 36 mg/m2 i.v. on days 1, 8, and 15 and capecitabine orally 625 mg/m2 b.i.d. from days 8 to 21. Cycles were repeated every 4 weeks. In the correlative study, we evaluated the TP expression by immunohistochemistry and the TP messenger RNA expression by real-time RT-PCR in the primary tumor. Results: Forty-seven women were enrolled. In the intention-to-treat analysis, objective responses were achieved in 24 patients (51%). Fourteen additional patients (30%) had stable disease. The median time to progression (TTP) was 6 months (range 1-44 months). Median survival was 17 months (range 1-48 months). Overall, the treatment was well tolerated. The most common clinical adverse events (all grades) were alopecia (55%), nail changes (53%), fatigue/asthenia (51%), nausea/ vomiting (51%), neutropenia (49%), and neuropathy (49%). A significantly higher TTP was observed in patients with TP-positive tumors (log-rank test, P = 0.009). Interestingly, a subgroup analysis confirmed this TTP benefit in patients with TP-positive tumors obtaining a tumor response (log-rank test, P = 0.03), whereas the statistical significance was lost in nonresponders (log-rank test, P = 0.3). Conclusions: This study indicates that a regimen with low doses of capecitabine plus weekly docetaxel is active against MBC. The correlative analysis provides preliminary evidence that TP expression may be a predictive marker for therapeutic benefit.

Original languageEnglish
Pages (from-to)1541-1546
Number of pages6
JournalAnnals of Oncology
Volume19
Issue number9
DOIs
Publication statusPublished - 2008

Keywords

  • Capecitabine
  • Docetaxel
  • Metastatic breast cancer
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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