Department of Medical Oncology, Oncologisch Centrum UZ, Brussel, 1090 Brussels, Belgium.
Anticancer Res. 2009 Dec;29(12):5225-8.
The tyrosine kinase inhibitors (TKI) sunitinib and imatinib were shown to induce macrocytosis in patients with renal cell cancer (RCC) and gastrointestinal stromal tumors (GIST), presumably through inhibition of the c-KIT dependent signaling pathway of erythroid progenitor cells of the bone marrow.
Hematology charts of patients with RCC, breast cancer (BC), GIST, non-small cell lung cancer (NSCLC) and hepatocellular cancer (HCC), receiving single-agent sunitinib, imatinib, sorafenib, erlotinib and BI 2992 (Tovok) at the recommended dose for at least 3 months were reviewed retrospectively for the occurrence of macrocytosis.
Macrocytosis occurred in all patients with RCC and BC treated with sunitinib and in all patients with GIST treated with imatinib. The percentage increase of the mean corpuscular volume (MCV) of peripheral red blood cells (RBC) compared with baseline at 3, 6, 9 and 12 months was 12.4%, 16.8%, 16.6%, 12.7% and 0.7%, 5.6%, 5.9%, 5% with sunitinib and imatinib respectively. The values at 3, 6 and 9 months between both groups were significantly different. Sorafenib, erlotinib and BI 2992 did not induce macrocytosis.
Sunitinib-induced macrocytosis was not confined to patients with RCC alone but also occurred in patients with BC. Imatinib also induced macrocytosis in patients with GIST but to a significantly lower degree. Because both drugs were used at an effective pharmacodynamic dose inhibiting c-KIT, these data strongly suggest that pathways in addition to c-KIT and not common to both agents are involved in the TKI-induced macrocytosis.
酪氨酸激酶抑制剂（TKI）舒尼替尼和伊马替尼被证明可诱导肾细胞癌（RCC）和胃肠道间质瘤（GIST）患者发生巨幼细胞性贫血，推测这是通过抑制骨髓中红系祖细胞的 c-KIT 依赖性信号通路。
回顾性分析接受单药舒尼替尼、伊马替尼、索拉非尼、厄洛替尼和 BI 2992（Tovok）治疗至少 3 个月的 RCC、乳腺癌（BC）、GIST、非小细胞肺癌（NSCLC）和肝细胞癌（HCC）患者的血液学图表，以评估巨幼细胞性贫血的发生情况。
所有接受舒尼替尼治疗的 RCC 和 BC 患者以及所有接受伊马替尼治疗的 GIST 患者均发生巨幼细胞性贫血。与基线相比，3、6、9 和 12 个月时外周血红细胞（RBC）的平均红细胞体积（MCV）的百分比增加分别为 12.4%、16.8%、16.6%、12.7%和 0.7%、5.6%、5.9%、5%，舒尼替尼和伊马替尼组之间的这些值在 3、6 和 9 个月时均有显著差异。索拉非尼、厄洛替尼和 BI 2992 不会引起巨幼细胞性贫血。
舒尼替尼引起的巨幼细胞性贫血不仅局限于 RCC 患者，也发生在 BC 患者中。伊马替尼也会导致 GIST 患者发生巨幼细胞性贫血，但程度明显较低。由于两种药物均以有效药效剂量抑制 c-KIT，这些数据强烈表明，除了 c-KIT 之外，还涉及其他途径，这些途径与两种药物都不同，参与了 TKI 诱导的巨幼细胞性贫血。
