Mechanisms to improve chemotherapy effectiveness.

Although many effective anti-cancer agents are now available, their curative potential is compromised by a variety of problems related to tumor sensitivity, drug access, and pharmacokinetics. Central to the problem of inadequate chemotherapy is drug resistance. Drug resistance may be intrinsic, acquired, or induced, and it may develop to one drug or it may occur simultaneously to multiple agents (pleiotropic). Substantial progress has been made in our understanding of the mechanisms of drug resistance and techniques for overcoming that resistance. New evidence has emerged that highlights the importance of dose intensity in achieving successful drug treatment outcomes. Retrospective analysis of studies in breast, ovarian, colon cancer, and lymphoma suggest that new studies designed to optimize dose intensity may yield improved results. Several prospective trials have now corroborated the retrospectively derived importance of dose intensity as an independent factor in achieving improved survival. Finally, new techniques for drug delivery offer considerable promise. Chemotherapy by regional infusion and perfusion, implantable drug delivery systems, and continuous infusion of chemotherapy are unique novel techniques that may improve the efficacy of presently available chemotherapeutic agents even as new agents are developed.