Diéras V, Fumoleau P, Kalla S, Misset J L, Azli N, Pouillart P
Department of Medical Oncology, Curie Institute, Paris, France.
Eur J Cancer. 1997 Aug;33 Suppl 7:S20-2. doi: 10.1016/s0959-8049(97)90005-8.
The rationale for the development of a new drug combination is to combine optimal doses of drugs with single-agent activity that are not cross-resistant or have similar toxicities. Docetaxel, with its unique mechanism of action and its high response rates in metastatic breast cancer, provides both opportunities and challenges for the development of combination chemotherapy. Anthracyclines are widely accepted as the agents of choice for first-line treatment of metastatic breast cancer and they have been studied in combination with taxoids. Preliminary results with a combination of docetaxel and doxorubicin indicate an overall response rate of 74%, with the dose-limiting toxicities being neutropenia and infection. Vinorelbine also has single-agent activity against metastatic breast cancer and preclinical studies have demonstrated synergism when vinorelbine and docetaxel are combined. The dose-limiting toxicities of the vinorelbine-docetaxel combination are febrile neutropenia and mucositis. The overall response rate to treatment with this combination is 67%. We therefore conclude that docetaxel can be combined with doxorubicin or vinorelbine to provide high response rates and acceptable toxicity.
研发新的联合用药方案的基本原理是将具有单药活性、不存在交叉耐药性或毒性相似的药物的最佳剂量组合起来。多西他赛具有独特的作用机制，在转移性乳腺癌中具有较高的缓解率，这为联合化疗的研发带来了机遇和挑战。蒽环类药物被广泛认为是转移性乳腺癌一线治疗的首选药物，并且已对其与紫杉类药物的联合应用进行了研究。多西他赛与阿霉素联合应用的初步结果显示总缓解率为74%，剂量限制性毒性为中性粒细胞减少和感染。长春瑞滨对转移性乳腺癌也具有单药活性，临床前研究表明长春瑞滨与多西他赛联合应用时具有协同作用。长春瑞滨 - 多西他赛联合用药的剂量限制性毒性为发热性中性粒细胞减少和粘膜炎。该联合用药方案的总治疗缓解率为67%。因此，我们得出结论，多西他赛可与阿霉素或长春瑞滨联合应用，以提供较高的缓解率和可接受的毒性。
