title: Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin.
abstract: Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.
authors.affiliation: Department of Gastroenterology II, Vienna University School of Medicine, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Scheithauer
authors.forename: H
authors.initials: H
authors.lastname: Rosen
authors.forename: R
authors.initials: R
authors.lastname: Schiessel
authors.forename: J
authors.initials: J
authors.lastname: Schüller
authors.forename: M
authors.initials: M
authors.lastname: Karall
authors.forename: F
authors.initials: F
authors.lastname: Ernst
authors.forename: C
authors.initials: C
authors.lastname: Sebesta
authors.forename: G
authors.initials: G
authors.lastname: Kornek
authors.forename: E
authors.initials: E
authors.lastname: Hentschel
authors.forename: A
authors.initials: A
authors.lastname: Marczell
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; 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; D004341:Drug Evaluation; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil