title: Capecitabine with/without mitomycin C: results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma.
abstract: OBJECTIVE
  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/m(2) day 1-14 alone (ARM A) or in combination with mitomycin C 6 mg/m(2) 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.
authors.affiliation: Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. cereda.stefano@hsr.it.
authors.forename: S
authors.initials: S
authors.lastname: Cereda
authors.affiliation: Istituto Nazionale Tumori Regina Elena, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Milella
authors.affiliation: Struttura Complessa di Oncologia Medica Ospedale Garibaldi, Catania, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cordio
authors.affiliation: Candiolo Cancer Institute - FPO, IRCCS, Università degli Studi di Torino, Turin, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Leone
authors.affiliation: A.O.U. Santa Maria della Misericordia, Udine, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Istituto Oncologico Veneto - IRCCS, Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Galiano
authors.affiliation: A.O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mosconi
authors.affiliation: A.O. Universitaria Pisana, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vasile
authors.affiliation: Università Campus Bio-Medico, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.affiliation: Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Belli
authors.affiliation: A.O. Universitaria Integrata, Verona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Auriemma
authors.affiliation: A.O. Città della Salute e della Scienza, Turin, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Novarino
authors.affiliation: Istituto Nazionale Tumori Regina Elena, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Vaccaro
authors.affiliation: Struttura Complessa di Oncologia Medica Ospedale Garibaldi, Catania, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Martines
authors.affiliation: Candiolo Cancer Institute - FPO, IRCCS, Università degli Studi di Torino, Turin, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Marino
authors.affiliation: A.O.U. Santa Maria della Misericordia, Udine, Italy.
authors.forename: S E
authors.initials: SE
authors.lastname: Lutrino
authors.affiliation: Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Palazzo
authors.affiliation: CLIOSS, Nerviano, Milano, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Reinach
authors.affiliation: Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Aldrighetti
authors.affiliation: Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Reni
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D013939:Thymidine Phosphorylase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D016685:Mitomycin; D000069287:Capecitabine; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase
keywords: Biliary tract cancer; Capecitabine; Mitomycin C; Second-line therapy; Thymidine phosphorylase; Thymidylate synthase