Effects of amifostine and paclitaxel on growth of human ovarian carcinoma xenografts in the severe combined immune-deficient mouse: preliminary results.

The effects of amifostine on paclitaxel-induced tumor growth delay using in vivo human ovarian cancer models were evaluated. In some mouse strains amifostine causes hypothermia and/or vasodilation, leading to increased spleen weight and ascites that can result in experimental artifacts. We found, however, that amifostine alone at 100 or 200 mg/kg intraperitoneally did not substantially alter body weight, spleen weight, or body temperature in severe combined immune-deficient (scid) mice bearing human 2780 ovarian cancer cells. In a model of minimal tumor burden (tumor cells injected subcutaneously day 0, drug treatment started day 1) scid mice receiving paclitaxel (27 mg/kg intraperitoneally) with or without amifostine had increased survival at day 76 (83% to 100%) compared with mice that did not receive paclitaxel (17% to 33%). For a model of advanced ovarian cancer, mice received tumor cell injections on day 0 and did not begin drug treatment until tumors were palpable (0.2 x 0.2 cm). Paclitaxel given for five repetitive doses significantly decreased tumor growth (P = .0001) in the advanced ovarian cancer model, and these results were the same whether or not mice received amifostine prior to each paclitaxel dose. We conclude that the scid mouse is a good model for evaluating amifostine in vivo, and that there was no evidence of amifostine-induced tumor protection in these scid mouse human ovarian cancer models. In future studies we will evaluate whether the cytoprotective effects of amifostine will allow dose escalation of paclitaxel and result in enhanced antitumor effects.