A hypothesis concerning the relationship of cellular pharmakokinetics to optimal scheduling of anti-cancer agents

Abstract

It is well recognized that the degree of toxicity, type of toxicity, and therapeutic to toxic ratio of most anti-cancer agents are dependent upon schedule. It is postulated that an optimal schedule is one that creates the largest possible difference in uptake of drug between neoplastic and normal cells, especially those cells that by their death limit the amount of drug that can be given to the patient. Specific pharmacokinetic parameters can be determined that optimize the relative distribution of drug between neoplastic tissues and dose-limiting normal tissues, and thus may permit optimization of schedule.