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.