Young R C
Fox Chase Cancer Center, Philadelphia, PA 19111.
Cancer. 1990 Feb 1;65(3 Suppl):815-22. doi: 10.1002/1097-0142(19900201)65:3+<815::aid-cncr2820651329>3.0.co;2-f.
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.
尽管现在有许多有效的抗癌药物，但由于与肿瘤敏感性、药物可达性和药代动力学相关的各种问题，它们的治愈潜力受到了损害。化疗效果不佳问题的核心是耐药性。耐药性可能是内在的、获得性的或诱导性的，它可能对一种药物产生，也可能同时对多种药物产生（多向性）。我们在理解耐药机制和克服耐药的技术方面取得了重大进展。新的证据表明了剂量强度在实现成功药物治疗结果方面的重要性。对乳腺癌、卵巢癌、结肠癌和淋巴瘤研究的回顾性分析表明，旨在优化剂量强度的新研究可能会产生更好的结果。现在有几项前瞻性试验证实了回顾性得出的剂量强度作为实现生存率提高的独立因素的重要性。最后，新的药物递送技术有很大的前景。通过区域输注和灌注、可植入药物递送系统以及化疗的持续输注进行化疗是独特的新技术，即使在开发新药物的同时，这些技术也可能提高现有化疗药物的疗效。
