Plosker G L, Faulds D
Adis International Limited, Auckland, New Zealand.
Drugs. 1993 May;45(5):788-856. doi: 10.2165/00003495-199345050-00011.
Epirubicin is the 4' epimer of the anthracycline antibiotic doxorubicin, and has been used alone or in combination with other cytotoxic agents in the treatment of a variety of malignancies. Comparative and noncomparative clinical trials have demonstrated that regimens containing conventional doses of epirubicin achieved equivalent objective response rates and overall median survival as similar doxorubicin-containing regimens in the treatment of advanced and early breast cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), non-Hodgkin's lymphoma, ovarian cancer, gastric cancer and nonresectable primary hepatocellular carcinoma. Recently, dose-intensive regimens of epirubicin have achieved high response rates in a number of malignancies including early and advanced breast cancer and lung cancer. The major acute dose-limiting toxicity of anthracyclines is myelosuppression. In vitro and clinical studies have shown that, at equimolar doses, epirubicin is less myelotoxic than doxorubicin. The lower haematological toxicity of epirubicin, as well as the recent introduction of supportive measures such as colony-stimulating factors, has allowed dose-intensification of epirubicin-containing regimens, which is particularly significant because of the definite dose-response relationship of anthracyclines. Cardiotoxicity, which is manifested clinically as irreversible congestive heart failure and/or cardiomyopathy, is the most important chronic cumulative dose-limiting toxicity of anthracyclines. Epirubicin has a lower propensity to produce cardiotoxic effects than doxorubicin, and its recommended maximum cumulative dose is almost double that of doxorubicin, thus allowing for more treatment cycles and/or higher doses of epirubicin. In summary, dose-intensive epirubicin-containing regimens, which are feasible due to its lower myelosuppression and cardiotoxicity, have produced high response rates in early breast cancer, a potentially curable malignancy, as well as advanced breast, and lung cancers. Furthermore, there is evidence to suggest that improved response rates can improve quality of life in some clinical settings, but whether this leads to prolonged survival has not yet been determined. Recently implemented supportive measures such as colony-stimulating factors, prophylactic antimicrobials and peripheral blood stem cell support may help achieve other potential advantages of dose-intensive epirubicin-containing regimens such as reductions in morbidity and length of hospital admissions.
表柔比星是蒽环类抗生素多柔比星的4'差向异构体，已单独或与其他细胞毒性药物联合用于治疗多种恶性肿瘤。比较性和非比较性临床试验表明，在治疗晚期和早期乳腺癌、非小细胞肺癌（NSCLC）、小细胞肺癌（SCLC）、非霍奇金淋巴瘤、卵巢癌、胃癌和不可切除的原发性肝细胞癌时，含常规剂量表柔比星的方案与含多柔比星的类似方案相比，客观缓解率和总中位生存期相当。最近，表柔比星的剂量密集方案在包括早期和晚期乳腺癌及肺癌在内的多种恶性肿瘤中取得了高缓解率。蒽环类药物的主要急性剂量限制性毒性是骨髓抑制。体外和临床研究表明，在等摩尔剂量下，表柔比星的骨髓毒性低于多柔比星。表柔比星较低的血液学毒性，以及最近引入的集落刺激因子等支持措施，使得含表柔比星方案的剂量强化成为可能，这一点尤为重要，因为蒽环类药物存在明确的剂量反应关系。心脏毒性在临床上表现为不可逆的充血性心力衰竭和/或心肌病，是蒽环类药物最重要的慢性累积剂量限制性毒性。表柔比星产生心脏毒性作用的倾向低于多柔比星，其推荐的最大累积剂量几乎是多柔比星的两倍，因此可以进行更多的治疗周期和/或更高剂量的表柔比星治疗。总之，由于表柔比星较低的骨髓抑制和心脏毒性，含表柔比星的剂量密集方案是可行的，在早期乳腺癌（一种潜在可治愈的恶性肿瘤）以及晚期乳腺癌和肺癌中产生了高缓解率。此外，有证据表明，在某些临床情况下，缓解率的提高可以改善生活质量，但这是否会导致生存期延长尚未确定。最近实施的支持措施，如集落刺激因子、预防性抗菌药物和外周血干细胞支持，可能有助于实现含表柔比星剂量密集方案的其他潜在优势，如发病率降低和住院时间缩短。
