Chemosensitivity of human melanoma to cisplatin and heat at pharmacokinetic doses achievable by isolated hyperthermic perfusion

S. P.L. Leon, M. J. Xu, D. S. Alberts, T. F. Wang, Y. M. Peng, E. M. Hersh, C. W. Taylor, P. Fanta, S. E. Salmon

Research output: Contribution to journalArticle

Abstract

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 languageEnglish (US)
Pages (from-to)216-219
Number of pages4
JournalRegional Cancer Treatment
Volume4
Issue number5-6
StatePublished - Dec 1 1992

ASJC Scopus subject areas

  • Oncology
  • Pharmacology

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    Leon, S. P. L., Xu, M. J., Alberts, D. S., Wang, T. F., Peng, Y. M., Hersh, E. M., Taylor, C. W., Fanta, P., & Salmon, S. E. (1992). Chemosensitivity of human melanoma to cisplatin and heat at pharmacokinetic doses achievable by isolated hyperthermic perfusion. Regional Cancer Treatment, 4(5-6), 216-219.