Phase-I clinical trial of sodium cyanate in patients with advanced colorectal carcinoma.
Sodium cyanate, a drug that selectively suppresses amino acid incorporation for protein synthesis in tumor tissue, was given to patients with advanced colorectal carcinoma who had failed to conventional therapy, with the purpose of assessing a maximum tolerable oral dose. At 35 mg/kg p.o. daily, the drug had to be stopped in approximately half (4) of the patients because of gastrointestinal toxicity (nausea, vomiting) and neurologic toxicity (hallucinations, disorientation). However, in 5 other patients, at the same dose, the drug was well tolerated for up to 147 days and for a total cumulative dose of 308 g. In this group of patients, sodium cyanate was stopped because of evidence of tumor progression. No hematologic toxicity was observed. We observed no therapeutic effects. We therefore recommend a starting dose of 30 mg/kg p.o. if a phase-II study is considered.
D000328:Adult; D000368:Aged; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003485:Cyanates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy*
D003485:Cyanates; C009281:sodium cyanate