EFFECTIVENESS OF CISPLATIN, PACLITAXEL, AND SURAMIN AGAINST HUMAN-MALIGNANT MESOTHELIOMA XENOGRAFTS IN ATHYMIC NUDE-MICE

Background and Objectives: Malignant mesothelioma has a poor prognosis and is refractory to many agents. The antitumor effectiveness of cisp latin, paclitaxel, and suramin as single agents and in combination was evaluated in vivo against four lines of human pleural malignant mesot helioma xenografts in athymic nude mice, including one epithelial type and three fibrosarcomatous. Methods: After growth of tumors occurred by day 54 or 55, mice were randomized in groups of four each to receiv e either cisplatin 4 mg/kg intraperitoneally weekly x5, or paclitaxel (Taxol) 12.5 mg/kg subcutaneously daily 5 days/week for 3 consecutive weeks, or suramin 60 mg/kg intraperitoneally daily x4,versus controls treated with normal saline. Results: Cisplatin was very effective agai nst one line and also to a lesser degree against another line. Paclita xel showed antitumor effects similar to cisplatin, being very effectiv e in one line, and also showed good activity in another line. Suramin was basically inactive in all four lines. Following the results obtain ed with these single agents, it was decided to evaluate the combinatio n of cisplatin and paclitaxel, which resulted in more pronounced antit umor effect in all four cell lines. Conclusions: These results indicat e that the combination of cisplatin and paclitaxel is superior to each agent alone in this model, and that it deserves to be evaluated in pa tients with malignant mesothelioma. (C) 1998 Wiley-Liss, Inc.