Initial clinical studies with copovithane.
Copovithane is a new copolymer of low molecular weight and with a significant in vivo antitumor activity in preclinical trials. The mechanism of action is unknown. Ninety-one patients with various metastatic neoplasms beyond the curable stage were treated with copovithane by weekly intravenous administration. Dose levels ranged from 1 to 33 g/m2/week. No dose-limiting toxicity was reached. Tolerance was excellent, with minor fatigue, occasional nausea, and intermittent proteinuria as the only significant side effects in less than 25% of patients. Two patients achieved a partial remission, and five patients reached minor responses during therapy. Antitumor effects were noted only in cutaneous and subcutaneous metastases. Extensive immunologic evaluation revealed some improvement in helper:suppressor T cell ratio, in vitro cytotoxicity tests, and lymphocyte blastogenic responses in patients treated at intermediate levels. The immunologic testing also suggested that the higher dose levels (22-33 g/m2 weekly) might adversely affect the immune response. The clinical relevance of these changes is uncertain. Phase II clinical trials are recommended utilizing weekly doses between 10 and 15 g/m2.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004341:Drug Evaluation; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011205:Povidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D000970:Antineoplastic Agents; D002219:Carbamates; C038184:copovithane; D011205:Povidone