Phillip Veit, Zahel Tina, Bärtl Klaus, Rasch Sebastian, Ebert Oliver, Schmid Roland M, Rummeny Ernst, Algül Hana
II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Straße 22, 81675 München, Germany.
Institut für diagnostische und interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Straße 22, 81675 München, Germany.
Pancreatology. 2016 Jul-Aug;16(4):621-4. doi: 10.1016/j.pan.2016.02.010. Epub 2016 Feb 27.
BACKGROUND/OBJECTIVES: Angiogenesis plays a central role in tumor growth and metastasis and tyrosine kinases are crucial in the modulation of growth factor signaling. Several side effects of tyrosine kinase inhibitors have been reported, including diarrhea due to pancreatic insufficiency. The suspected mechanism is the anti-angiogenetic effect of the inhibited vascular endothelial growth factor (VEGF) causing a disturbance of the microvasculation. The aim of the present study was to determine the volume of the pancreas before and after a therapy both with the multi-tyrosine kinase inhibitor Sorafenib and Bevacizumab, which is a humanized monoclonal immunoglobulin G1 antibody against VEGF.
Retrospective monocentric study including 42 patients who received either Sorafenib, Bevacizumab combined with Flourouracil and/or Irinotecan, or singly Flourouracil and Irinotecan for different non-pancreatic malignancies. The volume of the pancreas was measured before and after therapy by CT-scan based volumetry.
The pancreatic volume was statistically significantly lower after treatment with Sorafenib (75.4 mL vs. 71.0 mL; p = 0.006) or Bevacizumab and Fluorouracil ± Irinotecan (71.8 mL vs. 62.6 mL; p = 0.020). The pancreatic volume did not change statistically significantly after treatment with Fluorouracil ± Irinotecan only (51.1 mL vs. 49.9 mL; p = 0.142).
Pancreatic volume decreases statistically significantly under treatment with both the multi-tyrosine kinase inhibitor Sorafenib and the angiogenesis inhibitor Bevacizumab. This volume reduction is most likely due to a reduced microvasculation by inhibition of VEGF.
背景/目的:血管生成在肿瘤生长和转移中起核心作用,酪氨酸激酶在生长因子信号调节中至关重要。已有报道酪氨酸激酶抑制剂有多种副作用,包括因胰腺功能不全导致的腹泻。推测的机制是被抑制的血管内皮生长因子(VEGF)的抗血管生成作用导致微血管循环紊乱。本研究的目的是确定在使用多酪氨酸激酶抑制剂索拉非尼和贝伐单抗(一种抗VEGF的人源化单克隆免疫球蛋白G1抗体)治疗前后胰腺的体积。
回顾性单中心研究,纳入42例因不同非胰腺恶性肿瘤接受索拉非尼、贝伐单抗联合氟尿嘧啶和/或伊立替康,或单独使用氟尿嘧啶和伊立替康治疗的患者。通过基于CT扫描的容积测定法在治疗前后测量胰腺体积。
使用索拉非尼治疗后胰腺体积在统计学上显著降低(75.4 mL对71.0 mL;p = 0.006),使用贝伐单抗和氟尿嘧啶±伊立替康治疗后也显著降低(71.8 mL对62.6 mL;p = 0.020)。仅使用氟尿嘧啶±伊立替康治疗后胰腺体积无统计学显著变化(51.1 mL对49.9 mL;p = 0.142)。
多酪氨酸激酶抑制剂索拉非尼和血管生成抑制剂贝伐单抗治疗均使胰腺体积在统计学上显著减小。这种体积减小很可能是由于VEGF受抑制导致微血管循环减少所致。