title: Assessment of infusional 5-fluorouracil schedule and dose intensity: a Southwest Oncology Group and Eastern Cooperative Oncology Group study.
abstract: BACKGROUND
  Building on results from Southwest Oncology Group trial 8905, this trial was designed to compare low-dose continuous infusion (LDCI) of 5-fluorouracil (5-FU) versus intermittent high-dose infusion (HDI) of 5-FU in disseminated colorectal cancer (CRC) for evidence of survival advantage based on dose intensity. A companion trial was funded to assess molecular parameters associated with fluoropyrimidine response or resistance and toxicity from these treatments.
  
  
  METHODS
  Eligibility included histologic diagnosis of disseminated CRC, measurable or evaluable disease, no previous therapy for metastatic disease, performance status of 0-2, and adequate renal, hepatic, cardiac, and hematologic function. Stratification factors were measurable versus evaluable disease, performance status of 0/1 versus 2, presence versus absence of adjuvant therapy, and presence versus absence of previous surgery and enrollment on the companion trial. Patients were randomized to receive (1) LDCI 5-FU 300 mg/m(2) per day for 28 days every 5 weeks or (2) HDI 5-FU 2,600 mg/m(2) for 24 hours each week.
  
  
  RESULTS
  Between April 1995 and May 1999, 730 patients were accrued (LDCI arm, n = 360; HDI arm, n = 370). Of these, 708 eligible patients were assessable for survival and 690 for toxicity. Median survival for both groups was 13 months. Toxicity was mild; < 10% of patients in both arms had grade > 4 events. There were 8 study-related deaths (1%). Less than 10% of patients were enrolled in the companion trial.
  
  
  CONCLUSIONS
  Increasing 5-FU dose intensity yields no survival advantage beyond that achieved with LDCI 5-FU. This study confirms the favorable toxicity profile of infusional 5-FU. Because no preferential benefit was observed for either infusion schedule, the more convenient weekly schedule should be considered for 5-FU-based combination regimens for disseminated CRC.
authors.affiliation: Comprehensive Cancer Center, Desert Regional Medical Center, Palm Springs, CA 92262, USA. gleichman@aptiumoncology.com
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Leichman
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Benedetti
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: Howard
authors.initials: H
authors.lastname: Hochster
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Shields
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: James L
authors.initials: JL
authors.lastname: Wade Iii
authors.forename: James D
authors.initials: JD
authors.lastname: Bearden Iii
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil