Activity of sequential low-dose methotrexate and fluorouracil in advanced colorectal carcinoma: attempt at correlation with tissue and blood levels of phosphoribosylpyrophosphate.
Forty-five patients with metastatic colorectal carcinoma were treated with low-dose methotrexate (MTX) and 5-fluorouracil (5-FU) given sequentially. The dose of MTX was 40 mg/m2 intravenously (IV) on days 1 and 8 followed 24 hours later by 5-FU at 600 mg/m2 IV on days 2 and 9; the drugs were recycled every 28 days. Fourteen (32%) of 43 adequately treated patients had a complete or partial response lasting a median of nine months (range, 6-15 + months). Four patients had a minor response and seven patients had stable disease for a median of nine and 10 months, respectively. Toxicity included mucositis in 28 (65%) patients, diarrhea in 18 (40%), nausea in 11 (24%), and vomiting in seven (16%). Hematologic toxicity was mild: six patients had nadir white blood cell counts less than 3.5 X 10(3) cells/microL, and seven patients had a nadir platelet count less than 100 X 10(3) cells/microL. Serial biopsies and blood samples were obtained in selected patients to evaluate the effect of MTX on tissue and lymphocyte phosphoribosylpyrophosphate (PRPP) and PRPP synthetase levels.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007970:Leukopenia / Q000139:chemically induced; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects; D009325:Nausea / Q000139:chemically induced; D010428:Pentosephosphates / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000097:blood / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D012268:Ribose-Phosphate Pyrophosphokinase / Q000097:blood / Q000378:metabolism*; D013921:Thrombocytopenia / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
D010428:Pentosephosphates; D010754:Phosphoribosyl Pyrophosphate; D010770:Phosphotransferases; D012268:Ribose-Phosphate Pyrophosphokinase; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate