Capecitabine with/without mitomycin C: Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma

S. Cereda, M. Milella, Stefano Cordio, F. Leone, G. Aprile, A. Galiano, S. Mosconi, E. Vasile, D. Santini, C. Belli, A. Auriemma, A. Novarino, V. Vaccaro, C. Martines, D. Marino, Eufemia Stefania Lutrino, V. Palazzo, B. Reinach, L. Aldrighetti, M. Reni

Research output: Contribution to journalArticle

Abstract

Purpose: Advanced biliary tract adenocarcinoma (BTA) is a rare tumor with a poor prognosis. Since no standard salvage chemotherapy regimen exists, we explored the activity of capecitabine alone or combined with mitomycin C. Methods: Patients aged 18-75 years and with KPS >50, with pathological diagnosis of BTA stratified based on site and stage of disease, were randomized to receive capecitabine 2000 mg/m2 day 1-14 alone (ARM A) or in combination with mitomycin C 6 mg/m2 day 1 (ARM B) as second-line therapy. Cycles were repeated in both arms every 3 weeks. Tumor assessment was performed every 2 months. The primary endpoint was the probability of being progression free at 6 months (PFS-6) from treatment start. According to the Fleming design, the study aimed to enroll 26 pts per arm. An exploratory endpoint was to assess thymidylate synthase (TS) and thymidine phosphorylase (TP) expression, as biomarkers predictive for clinical outcomes of capecitabine treatment. Results: Between October 2011 and 2013, 57 metastatic pts were enrolled: ARM A/B 28/29. Accordingly, 55 (26/29) pts were assessable for the primary endpoint: 2 (8 %) ARM A and 3 (10 %) ARM B pts were PFS-6. Main G3-4 toxicities were: hand-foot syndrome and transaminitis in 4/0 %, and thrombocytopenia, diarrhea and fatigue in 0/3 % of pts. No statistically significant correlation was found between TS or TP expression and pts' outcome. Conclusions: Since capecitabine yielded a disappointing outcome and the addition of mitomycin C did not improve the results, new therapeutic strategies need to be explored to improve survival in this disease setting. © 2015 Springer-Verlag Berlin Heidelberg.
Original languageEnglish
Pages (from-to)109-114
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume77
Issue number1
DOIs
Publication statusPublished - 2016

Keywords

  • Biliary tract cancer
  • Capecitabine
  • Mitomycin C
  • Second-line therapy
  • Thymidine phosphorylase
  • Thymidylate synthase
  • antineoplastic agent
  • capecitabine
  • mitomycin
  • thymidine phosphorylase
  • thymidylate synthase
  • adenocarcinoma
  • adult
  • aged
  • Biliary Tract Neoplasms
  • cancer staging
  • clinical trial
  • comparative study
  • controlled study
  • disease free survival
  • female
  • gene expression regulation
  • genetics
  • human
  • male
  • middle aged
  • pathology
  • phase 2 clinical trial
  • randomized controlled trial
  • treatment outcome
  • Adenocarcinoma
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Mitomycin
  • Neoplasm Staging
  • Thymidine Phosphorylase
  • Thymidylate Synthase
  • Treatment Outcome

Fingerprint Dive into the research topics of 'Capecitabine with/without mitomycin C: Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma'. Together they form a unique fingerprint.

  • Cite this

    Cereda, S., Milella, M., Cordio, S., Leone, F., Aprile, G., Galiano, A., Mosconi, S., Vasile, E., Santini, D., Belli, C., Auriemma, A., Novarino, A., Vaccaro, V., Martines, C., Marino, D., Lutrino, E. S., Palazzo, V., Reinach, B., Aldrighetti, L., & Reni, M. (2016). Capecitabine with/without mitomycin C: Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma. Cancer Chemotherapy and Pharmacology, 77(1), 109-114. https://doi.org/10.1007/s00280-015-2919-0