PHARMACOLOGICAL MANAGEMENT OF DRUG-RESISTANT GENITOURINARY TUMORS

The purpose of this article is to examine potentially useful treatment strategies for drug-resistant genitourinary (GU) tumors. To achieve the desired pharmacologic effect, adequate concentration vs time (C×T) drug kinetic profiles must be achieved at the target tissues. Inadequate C×T drug profiles can result from low vascular tissues, rapid drug metabolism, and insufficient dosing schedules. These factors may also contribute to the development of acquired drug resistance by enabling tumor cells to repair sublethal damage caused by cytotoxic drugs. Although the development of acquired drug resistance may represent a normal response to foreign agents and hence be inevitable in many tumors, dose-intensive regimens as first-line treatment may delay the clinical onset of resistance. Once acquired drug resistance does develop, several investigational treatment strategies aimed at biochemical mechanisms of resistance may further circumvent treatment failures. Finally, intrinsic drug resistance represents an additional problem in certain GU tumors, particularly renal cell carcinoma. In this case, dose-intensive treatment regimens that incorporate a chemosensitizing agent may prove to the useful as firstline therapy. Tumor-specific treatment regimens need to be developed based on many factors, including degree of intrinsic resistance, past chemotherapy, stage and site of disease, and patient tolerance to aggressive treatment regimens. © 1990 Springer-Verlag.