Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer?
Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer?
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DOI：
10.1007/s13539-014-0145-y
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发表时间：
2014-12-01
影响因子：
8.9
通讯作者：
Javle, Milind
中科院分区：
文献类型：
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作者：
Fogelman, David R.;Holmes, Holly;Javle, Milind
IGF-1在多种肿瘤类型的生长中发挥作用，包括胰腺癌。IGF-1也是肌肉的生长因子。IGF-1治疗靶点对肌肉质量的影响尚不清楚，我们评估了转移性胰腺癌（MPC）患者的L3肌肉质量，这些患者参加了MK-0646（M）的随机II期研究，MK-0646（M）是一种针对IGF-1蛋白的单克隆抗体。测试了两种不同剂量的M，5和10 mg/kg。我们使用Slice-o-matic（版本4.3）软件将CT图像分为肌肉和脂肪成分，并在基线和治疗2个月和4个月后测量肌肉面积（cm（2））。患者接受吉西他滨联合厄洛替尼（G + E）、G + E + M或G + M。组间差异采用t检验进行比较，53例患者的基线和2个月成像可用于分析。其中，42人在化疗时接受了M，11人仅接受了G + E。治疗2个月后，两组均显示肌肉质量下降。G + E组患者肌肉质量损失5.6%; M组患者在5和10 mg/kg治疗后分别损失9.1%和8.6%（p = 0.53）。与疾病稳定（9.6%）和疾病进展（8.9%，p = 0.14）患者相比，显示缓解的患者（中位数4.6%）肌肉损失较少。从基线到2个月成像的肌肉保留，定义为肌肉损失< 6 cm（2），与那些显示肌肉损失的患者相比，与更好的生存相关（HR 0.51，p = 0.03）。MPC患者即使从化疗中获得临床获益（PR或SD），也可以预期肌肉质量损失。肌肉损失与退出研究和死亡的风险相关。抗IGF-1 R治疗患者的肌肉质量损失无显著趋势。然而，目前尚不清楚这种损失是否会转化为患者之间的功能差异。
IGF-1 plays a role in the growth of multiple tumor types, including pancreatic cancer. IGF-1 also serves as a growth factor for muscle. The impact of therapeutic targeting of IGF-1 on muscle mass is unknown.We evaluated muscle mass at L3 in patients enrolled in a randomized phase II study of MK-0646 (M), a monoclonal antibody directed against the IGF-1 protein, in patients with metastatic pancreatic cancer (MPC). Two different doses of M were tested, 5 and 10 mg/kg. We used the Slice-o-matic (ver 4.3) software to segregate CT images into muscle and fat components and measured muscle area (cm(2)) at baseline and after 2 and 4 months of treatment. Patients received either gemcitabine with erlotinib (G + E), G + E + M, or G + M. Differences between the groups were compared using t tests.Fifty-three patients had both baseline and 2-month imaging available for analysis. Of these, 42 received M with their chemo, and 11 had G + E only. After 2 months of treatment, both groups demonstrated decrease in muscle mass. G + E patients lost 5.6 % of muscle mass; M patients lost 9.1 and 8.6 % after treatment with 5 and 10 mg/kg, respectively (p = 0.53). Patients demonstrating a response lost less muscle (median 4.6 %) than those with stable disease (9.6 %) and progressive disease (8.9 %, p = 0.14). Muscle retention from baseline to 2-month imaging, defined as loss of < 6 cm(2) of muscle, correlated with better survival than those patients demonstrating a muscle loss (HR 0.51, p = 0.03).MPC patients can be expected to lose muscle mass even while having clinical benefit (PR or SD) from chemotherapy. Muscle loss correlated with a risk of study drop-out and death. There was a non-significant trend toward greater muscle mass loss in patients on anti-IGF-1R therapy. However, it is unclear if this loss translates into functional differences between patients.