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PubMed1984

[Experimental toxicologic and therapeutic studies on the activity of the CMF(cyclophosphamide-methotrexate-5-fluorouracil) scheme versus the VMF(vincristine-methotrexate-5-fluorouracil) scheme].

Experimental administration of the CMF scheme, which is used in adjuvant chemotherapy in humans, resulted in carcinogenic effects in rats. When substituting cyclophosphamide by vincristine, no carcinogenic activity was observed. The therapeutic effect of the VMF scheme was approximately equivalent to that of the CMF scheme in various experimental designs. It is discussed whether in adjuvant chemotherapy combinations should rather be used which lack any long-term toxicity such as carcinogenic effects.

Animals↗
PubMedDate not supplied

Biochemical modulation of 5-fluorouracil with methotrexate in advanced colorectal cancer patients pretreated with adjuvant 5-fluorouracil and leucovorin.

PURPOSE: 5-fluoracil (5-FU) remains the standard treatment in advanced colorectal cancer patients. An increasing number of recurring patients, however, have already received this drug as adjuvant after surgery. An attempt to increase 5-FU cytotoxicity through biochemical modulation is justified in this setting. In our study, a combination regimen of methotrexate followed by 5-FU, with leucovorin rescue, was employed. METHODS: Patients were required to have symptomatic, measurable, inoperable lesions from colorectal cancer, recurring after adequate radical surgery of the primary tumor and adjuvant 5-FU + leucovorin concluded at least 3 months before recurrence. Patients received methotrexate. 250 mg/m2 as a 2-hour i.v. infusion, followed by two doses of 5-FU, 500 mg/m2 as i.v. bolus 1 hour and 21 hours after the end of methotrexate infusion. Leucovorin rescue, 15 mg orally every six hours for 7 times, was started 1 hour after the second 5-FU dose. The cycle was repeated every 2 weeks. RESULTS: Twenty-two patients entered the trial, and 21 were evaluable. An objective response was observed in one patient (4.8%), 7 patients (33.3%) obtained tumor regression < 50% or disease stabilization. Thirteen patients (61.9%) progressed. Median survival in the whole group was 11 months. Subjective responses were observed in 7 patients (33.3%). Toxicity was mild. CONCLUSIONS: Biochemical modulation with methotrexate does not seem a satisfactory means of increasing 5-FU activity, when the patient has been previously exposed to 5-FU plus leucovorin. On the other hand, any possible advantages in terms of quality and prolongation of life with this schedule were obtained at the cost of very acceptable toxicity.

Adult↗
PubMed2004

Adjuvant chemotherapy with oxaliplatin, in combination with fluorouracil plus leucovorin prolongs disease-free survival, but causes more adverse events in people with stage II or III colon cancer Abstracted from: Andre T, Boni C, Mounedji-Boudiaf L, et al. Multicenter international study of oxaliplatin/5-fluorouracil/leucovorin in the adjuvant treatment of colon cancer (MOSAIC) investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343-51.

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