title: Protracted venous infusion 5-fluorouracil and interferon-alpha in advanced and refractory colorectal cancer.
abstract: BACKGROUND
  The management of patients with advanced colorectal cancer remains dependent on the optimal use of 5-Fluorouracil (5-FU). Enhanced 5-FU activity can be achieved by either adding a modulator or by altering the administration schedule, in particular using a protracted venous infusion. Based on encouraging phase II data using bolus 5-FU and interferon-alpha, we designed a study to investigate the activity of this modulator in patients with colorectal cancer refractory to protracted venous infusion 5-FU.
  
  
  METHODS
  Patients with advanced colorectal cancer were treated with 5-FU (300 mg/m2/day) given as a protracted venous infusion via an indwelling central venous catheter and portable battery driven pump. At the time the tumour became refractory to 5-FU, interferon-alpha was added and further outcome evaluated.
  
  
  RESULTS
  One hundred twenty-four patients were entered on the study, 118 of whom had measurable disease. Fifty-two patients had previously received chemotherapy. The overall tumour response rate with infusional 5-FU was 33% (38/118), however in previously untreated patients was 42% (29/69) and 18% in those given prior chemotherapy (9/49). At the point of refractory disease 64 patients had interferon-alpha added to the 5-FU. Five patients (8%) showed an objective partial response following interferon-alpha addition. Patient toxicities on infusional 5-FU included hand-foot erythroderma, stomatitis and diarrhoea. There were only 15 episodes of grade 3 or 4 toxicity. The addition of interferon-alpha gave fever, lethargy, myelosuppression and depression, but did not increase the incidence or severity of 5-FU related toxicities. Of 67 patients with tumour related pain, 53 (79%) had an improvement in their symptoms. Median survival of the whole group was 7.5 months.
  
  
  CONCLUSIONS
  Protracted venous infusion 5-FU is an active and well tolerated palliative treatment for advanced colorectal cancer. The addition of interferon-alpha at the point of 5-FU refractory disease resulted in further significant response in a small number of patients. Further randomised studies, including quality-of-life end-points, are needed before the use of interferon-alpha can be recommended as a modulator of 5-FU in the clinical setting.
authors.affiliation: CRC Section of Medicine, Royal Marsden Hospital, Sutton, Surrey, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Findlay
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: A
authors.initials: A
authors.lastname: Norman
authors.forename: M
authors.initials: M
authors.lastname: Nicolson
authors.forename: H
authors.initials: H
authors.lastname: Ford
authors.forename: J
authors.initials: J
authors.lastname: Husband
authors.forename: C
authors.initials: C
authors.lastname: Evans
authors.forename: R
authors.initials: R
authors.lastname: Carter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003873:Dermatitis, Exfoliative / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012044:Regression Analysis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D005472:Fluorouracil