Capecitabine with/without mitomycin C

Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma

Stefano Cereda, Michele Milella, Stefano Cordio, Francesco Leone, Giuseppe Aprile, A. Galiano, S. Mosconi, E. Vasile, D. Santini, Carmen Belli, A. Auriemma, A. Novarino, V. Vaccaro, C. Martines, Donatella Marino, Stefania Lutrino, V. Palazzo, B. Reinach, Luca Aldrighetti, Michele 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.

Original languageEnglish
Pages (from-to)109-114
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume77
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

Biliary Tract
Mitomycin
Adenocarcinoma
Thymidine Phosphorylase
Thymidylate Synthase
Tumors
Hand-Foot Syndrome
Salvaging
Chemotherapy
Biomarkers
Therapeutics
Fatigue
Toxicity
Diarrhea
Neoplasms
Fatigue of materials
Drug Therapy
Capecitabine

Keywords

  • Biliary tract cancer
  • Capecitabine
  • Mitomycin C
  • Second-line therapy
  • Thymidine phosphorylase
  • Thymidylate synthase

ASJC Scopus subject areas

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

Cite this

Capecitabine with/without mitomycin C : Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma. / Cereda, Stefano; Milella, Michele; Cordio, Stefano; Leone, Francesco; Aprile, Giuseppe; Galiano, A.; Mosconi, S.; Vasile, E.; Santini, D.; Belli, Carmen; Auriemma, A.; Novarino, A.; Vaccaro, V.; Martines, C.; Marino, Donatella; Lutrino, Stefania; Palazzo, V.; Reinach, B.; Aldrighetti, Luca; Reni, Michele.

In: Cancer Chemotherapy and Pharmacology, Vol. 77, No. 1, 01.01.2016, p. 109-114.

Research output: Contribution to journalArticle

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, 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, vol. 77, no. 1, pp. 109-114. https://doi.org/10.1007/s00280-015-2919-0
Cereda, Stefano ; Milella, Michele ; Cordio, Stefano ; Leone, Francesco ; Aprile, Giuseppe ; Galiano, A. ; Mosconi, S. ; Vasile, E. ; Santini, D. ; Belli, Carmen ; Auriemma, A. ; Novarino, A. ; Vaccaro, V. ; Martines, C. ; Marino, Donatella ; Lutrino, Stefania ; Palazzo, V. ; Reinach, B. ; Aldrighetti, Luca ; Reni, Michele. / Capecitabine with/without mitomycin C : Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma. In: Cancer Chemotherapy and Pharmacology. 2016 ; Vol. 77, No. 1. pp. 109-114.
@article{c96a68b96dc2476d9f4223b9e87c3139,
title = "Capecitabine with/without mitomycin C: Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma",
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.",
keywords = "Biliary tract cancer, Capecitabine, Mitomycin C, Second-line therapy, Thymidine phosphorylase, Thymidylate synthase",
author = "Stefano Cereda and Michele Milella and Stefano Cordio and Francesco Leone and Giuseppe Aprile and A. Galiano and S. Mosconi and E. Vasile and D. Santini and Carmen Belli and A. Auriemma and A. Novarino and V. Vaccaro and C. Martines and Donatella Marino and Stefania Lutrino and V. Palazzo and B. Reinach and Luca Aldrighetti and Michele Reni",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/s00280-015-2919-0",
language = "English",
volume = "77",
pages = "109--114",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Capecitabine with/without mitomycin C

T2 - Results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma

AU - Cereda, Stefano

AU - Milella, Michele

AU - Cordio, Stefano

AU - Leone, Francesco

AU - Aprile, Giuseppe

AU - Galiano, A.

AU - Mosconi, S.

AU - Vasile, E.

AU - Santini, D.

AU - Belli, Carmen

AU - Auriemma, A.

AU - Novarino, A.

AU - Vaccaro, V.

AU - Martines, C.

AU - Marino, Donatella

AU - Lutrino, Stefania

AU - Palazzo, V.

AU - Reinach, B.

AU - Aldrighetti, Luca

AU - Reni, Michele

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Biliary tract cancer

KW - Capecitabine

KW - Mitomycin C

KW - Second-line therapy

KW - Thymidine phosphorylase

KW - Thymidylate synthase

UR - http://www.scopus.com/inward/record.url?scp=84954076440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954076440&partnerID=8YFLogxK

U2 - 10.1007/s00280-015-2919-0

DO - 10.1007/s00280-015-2919-0

M3 - Article

VL - 77

SP - 109

EP - 114

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 1

ER -