title: Continuous infusion of 5-fluorouracil with versus without low-dose, consecutive administration of cisplatin in advanced colorectal cancer. A prospective randomized phase II study.
abstract: Recently, the treatment of advanced gastric cancer by continuous infusion of 5-fluorouracil (5-FU) with low-dose cisplatin (CDDP) has improved efficacy without severe toxicities. The possible effectiveness of 5-FU+low-dose CDDP for colorectal cancer (CRC) is intriguing. One hundred fifty-five patients with far-advanced CRC including at least one measurable lesion were enrolled in a prospective randomized clinical trial funded by the Japanese Foundation for Multidisciplinary Treatment of Cancer. These patients were assigned to the two arms to assess the value of low-dose CDDP when added to a continuous intravenous infusion of 5-FU at a dose of 300 mg/m(2)/24 hrs in a one-week cycle consisting of 5 days of treatment and 2 days of rest for at least 12 weeks. CD-DP was given intravenously at a dose of 3 mg/m(2) on days 1-5 and days 8-12, and then at a dose of 7 mg/m(2) twice a week. Three patients were excluded from the trial. The response rate in the 5-FU+low-dose CDDP arm (n=75) was significantly higher than that in the 5-FU arm (n=77) (25.3% vs. 11.7%; P = 0.037). There was no significant difference in the median overall survival time between the 5-FU+low-dose CDDP arm and the 5-FU arm (479 and 491 days, respectively). Grades 3/4 toxicities occurred infrequently in both arms. The quality of life was almost the same between the arms. Low-dose CDDP improved the response rate while keeping toxicities within clinically acceptable limits. However, this combined treatment did not confer a survival advantage over treatment with continuous infusion of 5-FU alone for patients with far-advanced CRC; that might be attributable to the short CDDP administration setting of 12 weeks.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. bunzo@med.osaka-cu.ac.jp
authors.forename: B
authors.initials: B
authors.lastname: Nakata
authors.forename: M
authors.initials: M
authors.lastname: Sowa
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.forename: T
authors.initials: T
authors.lastname: Kamano
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Fukunaga
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Tsujitani
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
authors.forename: Y
authors.initials: Y
authors.lastname: Mitachi
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Araki
authors.forename: S
authors.initials: S
authors.lastname: Yamamitsu
authors.forename: K
authors.initials: K
authors.lastname: Hirakawa
authors.forename: S
authors.initials: S
authors.lastname: Tominaga
authors.forename: T
authors.initials: T
authors.lastname: Shirasaka
authors.forename: K
authors.initials: K
authors.lastname: Inokuchi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil