title: Oxaliplatin and fixed-rate infusional gemcitabine in the second-line treatment of patients with metastatic colon cancer: final results of a Phase II trial prematurely closed as a result of poor accrual.
abstract: BACKGROUND
  Second-line therapy of advanced colorectal cancer (CRC) after failure of a combination of irinotecan, a fluoropyrimidine, and bevacizumab includes the use of oxaliplatin and a fluoropyrimidine. In animal models, synergistic effects of gemcitabine and platinum agents have been established. Additionally, superior antitumor activity of prolonged administration of gemcitabine compared with bolus administration has been demonstrated in vivo against murine colon tumors.
  
  
  METHODS
  A 2-stage phase II trial was developed to assess the efficacy (primary endpoint: response rate) and safety of gemcitabine 1000 mg/m(2) over 100 minutes on days 1 and 15 in combination with oxaliplatin 100 mg/m(2) over 2 hours on days 2 and 16, every 4 weeks. Patients with metastatic CRC in whom irinotecan and a fluoropyrimidine treatment had failed were enrolled. Calcium and magnesium infusion was routinely given before and after oxaliplatin administration.
  
  
  RESULTS
  Because of slow accrual as a result of oxaliplatin becoming more commonly used in first-line treatment, the trial was stopped with only 10 patients enrolled. Eight were men and 2 were women. Median age was 58.5 years (range, 47-72 years). Nine patients had an Eastern Cooperative Oncology Group performance status of 0/1. A median of 3.5 cycles was administered (range, 1-9; total, 42). Six patients had stable disease and 1 had progressive disease. Two patients had confirmed partial responses, and 1 patient had a partial response but developed necrotizing fasciitis, declined surgical treatment, and died before a confirmatory scan could be performed. The regimen was otherwise well tolerated: 1 patient developed grade 3 neutropenia. With a median follow-up of 5.5 months, 4 patients have died. The time to treatment failure was 3.7 months.
  
  
  CONCLUSIONS
  Despite premature study closure because of poor accrual, oxaliplatin in combination with fixed-rate infusional gemcitabine seems to be a safe and potentially effective regimen in the treatment of CRC. Further studies should be considered with the addition of targeted therapy.
authors.affiliation: Department of Oncology, Johns Hopkins Singapore International Medical Center, Singapore, Republic of Singapore. glopes@imc.jhmi.edu
authors.forename: Gilberto
authors.initials: G
authors.lastname: Lopes
authors.forename: Jose
authors.initials: J
authors.lastname: Quesada
authors.forename: Eugene
authors.initials: E
authors.lastname: Ahn
authors.forename: Aurea
authors.initials: A
authors.lastname: Flores
authors.forename: Afonso
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Caio Max
authors.initials: CM
authors.lastname: Rocha-Lima
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D016879:Salvage Therapy; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin; D003841:Deoxycytidine; D000093542:Gemcitabine