title: Mitomycin C and capecitabine combination (MiXe) in heavily pretreated metastatic breast cancer patients. A dose-finding study.
abstract: BACKGROUND
  No standard chemotherapy has been defined for metastatic breast cancer patients pretreated with anthracyclines and taxanes. In preclinical studies, mitomycin C (MMC) and capecitabine showed a synergistic effect by up-regulation of thymidine phosphorylase, and both drugs were active against breast cancer with a lack of overlapping toxicity, making their combination a well-tolerated regimen.
  
  
  METHODS
  A dose-finding study was carried out in order to determine the maximum tolerable dose of MMC combined with fixed-dose capecitabine and to describe the dose-limiting toxicities.
  
  
  RESULTS
  Twenty-one patients were enrolled, with metastatic breast cancer pretreated at least with anthracyclines and taxanes (3 at dose level I, 15 at dose level II, 3 at dose level III). At dose level III (MMC 12 mg/m2 and capecitabine 1000 mg/m2 days 2-15) dose-limiting toxicities were recorded in 2 patients (G4 thrombocytopenia, neutropenic fever, G4 neutropenia); dose level II (MMC 10 mg/m2 and capecitabine 1000 mg/m2 days 2-15) was extended for a better safety evaluation. No severe toxicity was noted at this dose level, and therefore this dose was recommend for the phase II study. With regard to activity, 4 partial responses and 2 stable diseases (28%) were recorded.
  
  
  CONCLUSIONS
  Our data show that the combination is feasible, well tolerated and active in this set of patients.
authors.affiliation: Unità Operativa di Oncologia Medica, A.O. Bianchi-Melacrino-Morelli Reggio Calabria, Italy. maisano@supereva.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Maisano
authors.forename: Nicola
authors.initials: N
authors.lastname: Caristi
authors.forename: Marzia
authors.initials: M
authors.lastname: Mare
authors.forename: Antonino
authors.initials: A
authors.lastname: Mafodda
authors.forename: Rita
authors.initials: R
authors.lastname: Carboni
authors.forename: Erika
authors.initials: E
authors.lastname: Montalto
authors.forename: Monica
authors.initials: M
authors.lastname: Iorfida
authors.forename: Mario
authors.initials: M
authors.lastname: Nardi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil