Wasan K M, Goss P E, Pritchard P H, Shepherd L, Palmer M J, Liu S, Tu D, Ingle J N, Heath M, Deangelis D, Perez E A
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
Ann Oncol. 2005 May;16(5):707-15. doi: 10.1093/annonc/mdi158. Epub 2005 Apr 7.
The purpose of this study was to evaluate changes in serum lipid parameters {cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and lipoprotein(a) [Lp(a)]}, in postmenopausal women receiving letrozole or placebo after adjuvant tamoxifen for early stage breast cancer (NCIC CTG MA.17L).
MA.17L is a substudy of MA.17, a randomized, double-blind, placebo-controlled trial of letrozole 2.5 mg taken daily for 5 years in postmenopausal women with primary breast cancer completing approximately 5 years of prior adjuvant tamoxifen. Patients consenting to participate in this companion study had blood drawn and lipid parameters (total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a), triglycerides) evaluated at baseline, 6 months, 12 months and yearly thereafter until completion of protocol therapy. It was required that women be non-hyperlipidemic and not taking lipid-lowering drugs at time of entry on this trial.
Three hundred and forty seven women were enrolled in the study. The letrozole and the placebo groups demonstrated marginally significant differences in the percentage change from baseline in HDL cholesterol at 6 months (P=0.049), in LDL cholesterol at 12 months (P=0.033) and triglycerides at 24 months (P=0.036). All comparisons of lipid parameters at other time points were not significantly different between the two treatment groups. No statistically significant differences in the number of patients exceeding the thresholds defined for the lipid parameters were found between the two treatment groups.
The MA.17 trial demonstrated a significant improvement in disease-free survival with the use of letrozole as extended adjuvant therapy post tamoxifen. Results from this study suggests that letrozole does not significantly alter serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or Lp(a) in non-hyperlidiemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy. These findings further support the tolerability of extended adjuvant letrozole in postmenopausal women following standard tamoxifen therapy.
本研究旨在评估早期乳腺癌患者在辅助使用他莫昔芬后接受来曲唑或安慰剂治疗的绝经后女性的血脂参数变化（胆固醇、高密度脂蛋白（HDL）胆固醇、低密度脂蛋白（LDL）胆固醇、甘油三酯和脂蛋白（a）[Lp（a）]）（NCIC CTG MA.17L）。
MA.17L是MA.17的一项子研究，MA.17是一项随机、双盲、安慰剂对照试验，对完成约5年辅助他莫昔芬治疗的绝经后原发性乳腺癌女性患者，每日服用2.5mg来曲唑，持续5年。同意参与这项配套研究的患者在基线、6个月、12个月时进行采血，并评估血脂参数（总胆固醇、HDL胆固醇、LDL胆固醇、Lp（a）、甘油三酯），此后每年评估一次，直至方案治疗结束。要求女性在进入本试验时无高脂血症且未服用降脂药物。
347名女性参与了本研究。来曲唑组和安慰剂组在6个月时HDL胆固醇自基线的百分比变化（P = 0.049）、12个月时LDL胆固醇（P = 0.033）以及24个月时甘油三酯（P = 0.036）方面显示出边缘性显著差异。两个治疗组在其他时间点的血脂参数所有比较均无显著差异。两个治疗组之间在超过血脂参数定义阈值的患者数量上未发现统计学显著差异。
MA.17试验表明，使用来曲唑作为他莫昔芬后的延长辅助治疗可显著改善无病生存期。本研究结果表明，对于至少接受5年辅助他莫昔芬治疗后接受长达36个月治疗的绝经后原发性乳腺癌非高脂血症女性，来曲唑不会显著改变血清胆固醇、HDL胆固醇、LDL胆固醇、甘油三酯或Lp（a）。这些发现进一步支持了绝经后女性在标准他莫昔芬治疗后延长辅助使用来曲唑的耐受性。
