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

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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.

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Acknowledgments

An unrestricted Grant of Rete Oncologica Lombarda (ROL)—Regione Lombardia—supported this trial.

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Authors and Affiliations

  1. Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy

    S. Cereda, C. Belli, V. Palazzo, L. Aldrighetti & M. Reni

  2. Istituto Nazionale Tumori Regina Elena, Rome, Italy

    M. Milella & V. Vaccaro

  3. Struttura Complessa di Oncologia Medica Ospedale Garibaldi, Catania, Italy

    S. Cordio & C. Martines

  4. Candiolo Cancer Institute – FPO, IRCCS, Università degli Studi di Torino, Turin, Italy

    F. Leone & D. Marino

  5. A.O.U. Santa Maria della Misericordia, Udine, Italy

    G. Aprile & S. E. Lutrino

  6. Istituto Oncologico Veneto - IRCCS, Padua, Italy

    A. Galiano

  7. A.O. Papa Giovanni XXIII, Bergamo, Italy

    S. Mosconi

  8. A.O. Universitaria Pisana, Pisa, Italy

    E. Vasile

  9. Università Campus Bio-Medico, Rome, Italy

    D. Santini

  10. A.O. Universitaria Integrata, Verona, Italy

    A. Auriemma

  11. A.O. Città della Salute e della Scienza, Turin, Italy

    A. Novarino

  12. CLIOSS, Nerviano, Milano, Italy

    B. Reinach

Authors
  1. S. Cereda
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  2. M. Milella
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  3. S. Cordio
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  4. F. Leone
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  5. G. Aprile
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  8. E. Vasile
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  9. D. Santini
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  10. C. Belli
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  12. A. Novarino
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  13. V. Vaccaro
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  14. C. Martines
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  15. D. Marino
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  16. S. E. Lutrino
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  17. V. Palazzo
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  18. B. Reinach
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  19. L. Aldrighetti
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  20. M. Reni
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Corresponding author

Correspondence to S. Cereda.

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Cereda, S., Milella, M., Cordio, S. et al. Capecitabine with/without mitomycin C: results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma. Cancer Chemother Pharmacol 77, 109–114 (2016). https://doi.org/10.1007/s00280-015-2919-0

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  • DOI: https://doi.org/10.1007/s00280-015-2919-0

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