The combination of 5-fluorouracil with misonidazole in patients with advanced colorectal cancer.
Misonidazole (MISO) has produced differential enhancement of tumor cell killing with a range of cytotoxic drugs including 5-fluorouracil (FU) in experimental mouse tumors and human xenografts. Since concomitant enhancement of normal tissue damage has been observed, a Phase I study of MISO and FU has been undertaken in patients with advanced colorectal cancer. Mild nausea and vomiting occurred more frequently after MISO and FU compared with FU alone; however, the incidence of leucopenia was similar with both treatment. No patients receiving the MISO/FU combination developed central nervous system toxicity or peripheral neuropathy. Twenty-four hour plasma nitroimidazole kinetics were analyzed and were not modified by the concomitant administration of the cytotoxic drug. Thus, in this preliminary study FU has been safely combined with MISO without significant modification of plasma nitroimidazole pharmacokinetics. Tumor regression was documented in 2/9 (22%) patients receiving more than 2 courses of MISO/FU. A Phase II study is proposed to investigate tumor response.
D003110:Colonic Neoplasms / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D008920:Misonidazole / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000188:drug therapy*
D009593:Nitroimidazoles; D008920:Misonidazole; D005472:Fluorouracil