CORRELATION OF DNA-PLOIDY AND S-PHASE FRACTION WITH CHEMOTHERAPEUTIC RESPONSE AND SURVIVAL IN A RANDOMIZED STUDY OF DISSEMINATED MALIGNANT-MELANOMA

DNA ploidy and S-phase fraction were measured by dow cytometry in the tumour tissue of 87 patients with disseminated malignant melanoma, who had been classified either as responders or with progressive disease in a study of the effects of 2 chemotherapeutic regimens. The patients had been randomized to receive treatment with dacarbazine (DTIC) and vindesine (Eldesine) with or without addition of cisplatin (Platinol). Tumour tissue was obtained from both the primary tumours and the last histologically verified metastases, but in some cases only the primar y tumours or the last metastases could be evaluated. There was a signi ficantly higher mean S-phase value in melanoma metastases from patient s with complete or partial responses compared with patients with progr essive disease. Neither the S-phase fraction of the primary tumour nor the DNA ploidy of the primary tumour or of the last histologically ve rified metastases taken before inclusion into the study were associate d with therapeutic response. In the multivariate analysis, both the an atomical location of the metastases and the S-phase fraction measured on the last metastases remained significant prognostic factors of resp onse. In the univariate survival analysis, there was an association be tween high S-phase fractions of the metastases and longer survival. In the multivariate survival analysis, the S-phase fraction, the number of involved metastatic sites and the treatment response were independe nt predictive factors. We conclude that, in disseminated melanoma trea ted with chemotherapy, a high S-phase fraction measured in the last hi stologically verified metastases is associated with a higher response rate and a longer survival. Our results clearly support the role of S- phase measurement as a potential tool for selecting patients for treat ment. (C) 1996 Wiley-Liss, Inc.