Bisagni G, Cocconi G, Scaglione F, Fraschini F, Pfister C, Trunet P F
Medical Oncology Division, University Hospital, Parma.
Ann Oncol. 1996 Jan;7(1):99-102. doi: 10.1093/oxfordjournals.annonc.a010490.
To evaluate the endocrine effects as well as the pharmacokinetic parameters, efficacy and safety of letrozole, a new fourth-generation non-steroidal aromatase inhibitor.
Fourteen postmenopausal women with progressive metastatic breast cancer, previously treated with endocrine therapy and/or chemotherapy for advanced disease, were treated with 0.5 mg daily doses of letrozole, orally. Endocrine and pharmacokinetic measurements were made before treatment and on days 14, 28, 56, and 84 of therapy.
Letrozole induced a >86% decrease in plasma estrone and a approximately 67% reduction in circulating estradiol from day 14 on. There was a statistically significant decrease in plasma cortisol, which appeared clinically irrelevant since all values remained within the normal range. No significant changes in aldosterone concentration were noted. One patient achieved a complete response (CR) and 4 patients a partial response (PR), with an objective response rate of 36% (95% CI 13% to 65%). Median duration of response was 24 months, ranging from 4 to 44 months. No toxic effects attributable to letrozole were noted in any patient.
Letrozole appears to be a very promising new antiaromatase drug. The characteristics of the patients more likely to respond, taking into account prior systemic treatment, should be defined by future studies. Further phase II and phase III studies comparing letrozole to other available second or even first-line endocrine-therapy agents, are warranted.
评估新型第四代非甾体类芳香化酶抑制剂来曲唑的内分泌效应、药代动力学参数、疗效及安全性。
14例绝经后进展期转移性乳腺癌妇女，先前已接受内分泌治疗和/或针对晚期疾病的化疗，口服每日剂量0.5mg来曲唑进行治疗。在治疗前及治疗的第14、28、56和84天进行内分泌和药代动力学测量。
从第14天起，来曲唑使血浆雌酮降低>86%，循环雌二醇降低约67%。血浆皮质醇有统计学意义的降低，但由于所有值均保持在正常范围内，临床意义不大。醛固酮浓度无显著变化。1例患者达到完全缓解（CR），4例患者达到部分缓解（PR），客观缓解率为36%（95%CI 13%至65%）。中位缓解持续时间为24个月，范围为4至44个月。未在任何患者中观察到来曲唑所致的毒性作用。
来曲唑似乎是一种非常有前景的新型抗芳香化酶药物。未来研究应确定在考虑既往全身治疗的情况下更可能有反应的患者特征。有必要开展进一步的II期和III期研究，将来曲唑与其他可用的二线甚至一线内分泌治疗药物进行比较。
