Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary

Sameh Mikhail, Maryam B. Lustberg, Amy S. Ruppert, Amir Mortazavi, Paul Monk, Barbara Kleiber, Miguel Villalona-Calero, Tanios Bekaii-Saab

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m2 bid, paclitaxel 60 mg/m2/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5 months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95 % CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity.

Original languageEnglish (US)
Pages (from-to)1005-1012
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number5
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Keywords

  • Capecitabine
  • Carboplatin
  • Carcinoma of unknown primary
  • Esophageal
  • Paclitaxel
  • Thymidine phosphorylase

ASJC Scopus subject areas

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

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