Phase II study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: Up-regulation of thymidine phosphorylase

Muhammad Wasif Saif, Glenda Black, Shalija Roy, Diana Bell, Suzanne Russo, Mohamed A. Eloubeidi, Adam Steg, Martin R. Johnson, Daniel Zelterman, Robert B. Diasio

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Purpose:: The objectives of this phase II study were to evaluate the effect of radiation (XRT) on thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and tumor necrosis factor α (TNF-α) and the efficacy of capecitabine-XRT in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS:: Twenty patients received 50.4 Gy XRT with capecitabine 1,600 mg/m on Monday through Friday for 6 weeks determined from our phase I study (Saif MW, Eloubeidi MA, Russo S, et al. J Clin Oncol. 2005;23:8679ĝ€"8687). After capecitabine-XRT, stable and responding patients received capecitabine 2,000 mg/m for 14 days every 3 weeks till progression. Restaging was performed every 9 weeks. Tumor specimens were procured with endoscopic ultrasound-fine needle aspiration before and at week 2 after capecitabine-XRT was started to evaluate the effect of XRT on TP, DPD, and TNF-α mRNA levels, determined by reverse transcriptase-polymerase chain reaction. RESULTS:: Among 20 patients, 4 (20%) had a partial response and 13 (65%) had stable disease. Two patients underwent surgical resection (10%). The 6-month survival rate was 84%, and the 1-year survival was 58%. Grade ĝ‰¥3 toxicities included nausea/vomiting (5%), thrombosis (5%), hyperbilirubinemia (5%), and grade 3 gastrointestinal bleeding (5%). TP was elevated during week 2 when compared with the pre-XRT TP (P ≤ 0.01). However, no such effect of XRT was found either on DPD (P ≤ 0.22) or on TNF-α (P ≤ 0.6). No correlation between TP and TNF-α was noticed. Also, no association between TP/DPD ratio and efficacy of capecitabine was identified. CONCLUSIONS:: This phase II study further confirms our phase I results and suggests that capecitabine-XRT is an effective, tolerable, and convenient alternative to an infusional 5-fluorouracil regimen for patients with pancreatic cancer. Although results support the use of capecitabine-XRT and TP was up-regulated, there appears to be additional genes associated with the response to capecitabine.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalCancer Journal
Volume13
Issue number4
DOIs
StatePublished - Jul 1 2007

Keywords

  • 5-fluorouracil
  • Capecitabine (Xeloda)
  • Dihydropyrimidine dehydrogenase
  • Pancreatic cancer
  • Radiotherapy
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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