title: [A clinical trial of a new mitomycin C derivative, KW-2083 (7-N-(p-hydroxyphenyl)-mitomycin C)].
abstract: KW-2083 [7-n-(p-hydroxyphenyl)-mitomycin C] is a new mitomycin C (MMC) derivative. Its myelotoxicity was compared with that of MMC by using colony-forming unit-spleen (CFU-S) from the femurs of C57BL/6 mice. As a result, it was estimated that the intensity of myelotoxicity of MMC was four times greater than that of KW-2083. Based on this data, a clinical trial of KW-2083 was conducted in 24 cases with various types of advanced solid tumors. KW-2083 was administered by i.v. injection at a dose of 40 mg/body every week. Out of 15 evaluable cases, a case of ovarian cancer showed a partial response. One case of each of ovarian cancer and gastric cancer showed minor response. However, as with mitomycin C, the dose-limiting toxicity of KW-2083 was leukopenia and thrombocytopenia. Other toxicities encountered were nausea, vomiting, anorexia, phlebitis and hepatic dysfunction. There were no cases with renal toxicity. Plasma concentration of KW-2083 was bioassayed in 3 cases who received 40 mg/body as an i.v. bolus injection. Plasma concentration-time curves fitted to a one-compartment model and half-life values averaged 27.6 min. The effective and low toxic dose schedules of KW-2083 should be investigated further.
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D003114:Colony-Forming Units Assay; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008875:Middle Aged; D016685:Mitomycin; D008937:Mitomycins / Q000097:blood / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy
chemical_list: D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; D016685:Mitomycin; C027281:7-N-(4-hydroxyphenyl)mitomycin C