Platinum drug delivery and radiation for locally advanced prostate cancer.
Combined therapies of cisplatin and radiation have resulted in clinical reports of apparent efficacious control of locoregional cancer and enhanced survival. Mechanisms of interaction between platinum and radiation that may explain these clinical observations all have in common the prediction that higher concentrations of platinum in all tumor cells close in time to irradiation should lead to greater potentiation of radiation-induced killing of those cells. Cisplatin is thus viewed as providing some radiation-equivalent, or a radiation dose-effect factor, for sterilization of tumors. One disease site that has not been well investigated for response to cisplatin plus radiation therapy, but that could benefit from it, is locally advanced prostate cancer. A body of literature now supports the view that local control of stage C (T3, N0, M0) prostate cancer is correlated with disease-free survival. This correlation makes prostate cancer a candidate for potentially achieving improved cure rates following local tumor sterilization by combining cisplatin with radiation therapy. The need and approaches to optimize delivery of cisplatin within tumor tissue is explored. Increasing cisplatin concentration to all the cells of a tumor, i.e., homogeneously delivering systemic high-dose cisplatin, should benefit the efficacious response otherwise expected for cisplatin combined with radiation. Strategies to increase the homogeneity of cisplatin delivery to a tumor are considered to be those that increase perfusion to that tumor. Vasoactive agents used in anticancer protocols are especially considered for their potential value in serving to increase tumor perfusion. These protocol-inclusive agents include certain cytokines and L-arginine antagonists, and should be better managed and accepted in practice compared to other vasoactive agents that need to be developed as specific additives to protocol designs.
Coughlin
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Dartmouth-Hitchcock Medical Center, Hanover, NH 03756.
Richmond
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D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors; D002460:Cell Line; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000628:therapy*; D011879:Radiotherapy Dosage
D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002945:Cisplatin