与他莫昔芬单一疗法相比，他莫昔芬和长效奥曲肽对胰岛素样生长因子系统的影响。

Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy.

作者信息

Helle S I, Mietlowski W, Guastalla J P, Szakolczai I, Bajetta E, Sommer H, Baltali E, Pinter T, Csepreghy M, Ottestad L, Boni C, Bryce C, Klijn J G M, Lønning P E

机构信息

Department of Medicine, Section of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway.

出版信息

Eur J Cancer. 2005 Mar;41(5):694-701. doi: 10.1016/j.ejca.2004.12.015. Epub 2005 Jan 21.

DOI:10.1016/j.ejca.2004.12.015

PMID:15763644

Abstract

The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-1 and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P<0.01 for all), but less suppression of IGFBP-2 (P<0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome.

摘要

在一项随机III期试验中，对150例乳腺癌患者的胰岛素样生长因子（IGF）系统进行了评估，该试验比较了帕莫酸奥曲肽与他莫昔芬联合他莫昔芬+安慰剂的疗效。比较了两个治疗组中IGF系统的变化以及个体结果的变化。在治疗前和治疗期间，通过放射免疫分析（RIA）/免疫放射分析（IRMA）测量血清IGF-I和-II、游离IGF-I以及胰岛素样生长因子结合蛋白1-3（IGFBP1-3），并通过Western配体印迹法（WLB）测量IGFBPs。与他莫昔芬单药治疗相比，联合治疗导致IGFBP-1升高幅度更大，对总IGF-I、游离IGF-I、IGF-II和IGFBP-3的抑制作用更强（所有P<0.01），但对IGFBP-2的抑制作用较小（P<0.05）。在总患者群体和联合治疗组中，IGFBP-2升高25%与无进展生存期（PFS）降低相关。两个治疗组的缓解率和疾病进展时间相似，这表明适度抑制循环中的IGF-I对临床结果没有影响。