title: Mitomycin-C and capecitabine as third-line chemotherapy in patients with advanced colorectal cancer: a phase II study.
abstract: OBJECTIVE
  The aim of this study was to investigate the therapeutic value and safety of third-line treatment with mitomycin-C (MMC) and capecitabine (Xeloda) in patients with advanced colorectal cancer pretreated with combination regimens including 5-fluorouracil (5-FU), folinic acid (FA) and irinotecan (CPT-11) or 5-FU, FA and oxaliplatin (L-OHP).
  
  
  METHODS
  A total of 21 patients (M/F 16/5, median age 60.0 years) with advanced colorectal cancer, all of whom had developed progressive disease while receiving or within 6 months of discontinuing two sequential chemotherapy lines with 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP, were accrued to this study. At the time of their relapse or progression, cytotoxic chemotherapy, consisting of intravenous MMC 7 mg/m(2) on therapeutic day 1 plus oral capecitabine 1000 mg/m(2) twice daily on days 1-14, was initiated. After rest for 7 days, capecitabine 1000 mg/m(2) twice daily was administered on days 22-35 followed by 7 days rest. Treatment courses were repeated every 6 weeks unless there was evidence of progressive disease, unacceptable toxicity or patient refusal of treatment.
  
  
  RESULTS
  All the patients were assessable for toxicity and 19 for response. The median number cycles of chemotherapy was two (range one to four). Only 1 patient (4.8%) had a partial response, 4 patients (19.0%) had stable disease, and 14 patients (66.7%) progressed. The median follow-up period was 7.3 months and median time to progression was 2.6 months. The median overall survival was 6.8 months. No toxic deaths occurred. Toxicities of third-line treatment were mild and manageable. As NCI/NIH common toxicity criteria, grade 3/4 anemia, neutropenia and thrombocytopenia occurred in two, one and one patients, respectively.
  
  
  CONCLUSIONS
  Our findings suggest that the combination of MMC and capecitabine in patients with advanced colorectal cancer pretreated with combination regimens including 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP is safe. However, this regimen had a poor response rate and no definitive contribution to increasing patients' overall survival time. Further evaluation of other salvage regimens seems to be warranted.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-Ku, Seoul 135-710, Korea.
authors.forename: Do Hyoung
authors.initials: DH
authors.lastname: Lim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Byeong-Bae
authors.initials: BB
authors.lastname: Park
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ji
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Keon Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Kihyun
authors.initials: K
authors.lastname: Kim
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil