title: Sequential trimetrexate, 5-fluorouracil and folinic acid are effective and well tolerated in metastatic colorectal carcinoma. The phase II study group of the AIO.
abstract: Trimetrexate (TMTX) is a new antifolate which avoids competition for cellular uptake with folinic acid (FA). A regimen of sequential TMTX, FA and 5-fluorouracil (5-FU) has shown efficacy in patients with colorectal cancer. Therefore, we treated 34 previously untreated patients with metastatic colorectal cancer with a weekly chemotherapy regimen consisting of 110 mg/m(2) of TMTX intravenously, then 24 h later 200 mg/m(2) of FA (i.v.) and 500 mg/m(2) of 5-FU (i. v.). Thereafter, 7 doses of oral FA (15 mg) were given at 6-hourly intervals. A treatment cycle consisted of 6 weeks of treatment, then 2 weeks of rest. All patients were treated as outpatients unless complications arose. Thirty-three patients were assessable for tumor response, and all 34 patients were assessable for toxicity. Twelve patients (36%; 95% confidence interval: 25-49%) achieved a partial response. The median duration of response was 8.5 months, and median survival was 14 months. The most common toxicity was diarrhea of grade 3/4, observed in 22% of treatment cycles; this decreased to 8% with early loperamide treatment. Hematologic toxicity was mild. The sequential administration of TMTX, FA and 5-FU is an active regimen in the first-line treatment of metastatic colorectal cancer and warrants further studies.
authors.affiliation: University Hospital 'Benjamin Franklin', Free University Berlin, Berlin, Germany. szelenyi@zedat.fu-berlin.de
authors.forename: H
authors.initials: H
authors.lastname: Szelényi
authors.forename: P
authors.initials: P
authors.lastname: Hohenberger
authors.forename: H
authors.initials: H
authors.lastname: Lochs
authors.forename: N
authors.initials: N
authors.lastname: Haboubi
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: E D
authors.initials: ED
authors.lastname: Kreuser
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D016597:Trimetrexate / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil; D016597:Trimetrexate