Using the human tumor cloning assay, we determined the sensitivity of human melanoma biopsies to cisplatin alone or in combination with heat (40°C) for 1 h. Single-cell suspensions were prepared from fresh surgical specimens histologically proven to be melanoma. Five of seven melanomas were found to be highly sensitive to cisplatin alone at 50 μg/ml (mean = 2.8% survival of tumor colonies, range = 0-7%). When a concentration of 5 μg/ml was used, tumor survival increased to a mean of 44.7% (range, 27.9%-71%). However, when heat (40°C) was used in combination with cisplatin at 5 μg/ml, significantly increased cytotoxicity was observed with survival being reduced to a mean of 23.6% (range = 14.1%-45.3%, P < 0.01, comparing tumor colony survival following cisplatin treatment at 5 μg/ml with or without heat). Pharmacokinetic studies of cisplatin in eight patients undergoing isolated hyperthermic perfusion for extremity melanomas using 75-100 mg/m2 cisplatin for 1 h indicated that the mean protein-free cisplatin levels in the isolated circuit at 5, 10, 20, 40 and 60 min were 36, 30, 26, 21 and 15 μg/ml respectively. Thus, it can be concluded that isolated hyperthermic perfusion of cisplatin was associated with levels greater than 15 μg/ml during the 1-h perfusion period. A preoperative in vitro chemosensitivity assay using cisplatin plus heat for extremity melanoma may be useful to select patients for isolated hyperthermic perfusion.
|Original language||English (US)|
|Number of pages||4|
|Journal||Regional Cancer Treatment|
|State||Published - Dec 1 1992|
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