Goldie J H
Division of Medical Oncology, University of British Columbia, Vancouver, Canada.
Recent Results Cancer Res. 1989;115:8-16. doi: 10.1007/978-3-642-83337-3_2.
We would suggest on the basis of our analysis that drug resistance still appears to represent a plausible explanation for drug treatment failure in adjuvant breast chemotherapy. It may not be the only factor, but, if present, clearly has to be circumvented if treatment results are to be improved. Since it seems most unlikely that a new wonder drug for breast cancer will emerge in the next few years, then it is to our existing armamentarium of antineoplastic agents that we will have to turn for improved therapeutic results. Fundamental questions will need to be asked about what indeed are the most appropriate agents to be used in combination chemotherapy protocols for this disease and what are the optimal dose ratios. Our own institutional experience in a number of areas has suggested that many chemotherapeutic protocols that are widely used represent significant underdosing and that achieving optimal results requires pushing therapeutic agents closer to the reasonable limits of tolerance. Enhanced techniques for patient support during programs of more intensive chemotherapy are now available, and it has also been our experience that patients tolerate briefer, intensive programs of chemotherapy better than they do protracted, less intensive protocols. The role of new drug combinations that incorporate synergistic or significant biochemical modulation effects (i.e., platinum-etoposide, 5-fluorouracil-leucovorin) need to be examined in the context of the management of breast cancer. We appear to have reached something of a plateau with existing protocols and approaches, and it is time to move ahead.
基于我们的分析，我们认为耐药性似乎仍是辅助性乳腺癌化疗中药物治疗失败的一个合理原因。它可能不是唯一的因素，但如果存在，显然要想提高治疗效果就必须加以克服。鉴于未来几年内似乎极不可能出现一种治疗乳腺癌的神奇新药，那么我们将不得不依靠现有的抗肿瘤药物来提高治疗效果。对于这种疾病，在联合化疗方案中究竟哪些是最合适的药物以及最佳剂量比是多少，需要提出一些根本性的问题。我们机构在多个领域的经验表明，许多广泛使用的化疗方案存在显著的剂量不足情况，要取得最佳效果就需要将治疗药物的剂量更接近合理的耐受极限。现在有了在更强化的化疗方案中为患者提供支持的增强技术，而且我们的经验还表明，患者对较短疗程的强化化疗方案的耐受性要优于长期的、强度较低的方案。需要在乳腺癌治疗的背景下研究包含协同或显著生化调节作用的新药组合（即铂类 - 依托泊苷、5 - 氟尿嘧啶 - 亚叶酸钙）的作用。我们似乎在现有方案和方法上已达到某种瓶颈，是时候向前迈进了。
