Sequential chemotherapy of advanced colorectal cancer with standard or high-dose methotrexate followed by 5-fluorouracil.
Thirty patients with advanced measurable colorectal cancer were randomized to receive either methotrexate (MTX) 200 mg/m2 or 40 mg/m2, followed in four hours by 5-fluorouracil (5-FU) 600 mg/m2. Patients receiving the higher dose MTX were given leucovorin rescue 24 hours later. Eight of 13 patients treated with 200 mg/m2 MTX + 5-FU developed severe hematologic toxicity, leading to two toxic deaths. In addition, 9/13 developed mild azotemia, and three patients had severe gastrointestinal toxicity. No patients with prior chemotherapy responded to either regimen. Among those without prior chemotherapy, there were two of six and three of eight partial responses, respectively, in the 200 mg/m2 and 40 mg/m2 MTX regimens. Sequential 200 mg/m2 MTX followed by 5-FU after four hours has unacceptable toxicity. Sequential treatment with standard dose MTX + 5-FU is tolerable and merits further study.
D000368:Aged; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004064:Digestive System / Q000187:drug effects; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007970:Leukopenia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy*; D014511:Uremia / Q000139:chemically induced
D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate