Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Leuk Res. 2014 Apr;38(4):430-4. doi: 10.1016/j.leukres.2013.10.026. Epub 2013 Nov 5.
Novel therapies for the treatment of acute myeloid leukemia are required to overcome disease resistance and to provide potentially less toxic therapies for older adults. Prior clinical trials involving patients with non-small cell lung cancer have demonstrated the safety and biologic activity of the administration of EGFR inhibitors in carefully selected patients. The potential efficacy of this approach in patients with acute myeloid leukemia is unknown. The effects of gefitinib on differentiation induction and cell viability in AML cell lines and primary patient AML cells were previously reported and cell viability was inhibited in a clinically achievable range. To determine if EGFR inhibitors would be therapeutically efficacious in advanced AML, we performed a phase II trial in which 18 patients with a median age of 72 (range, 57-84 years) were treated with gefitinib (750mg orally daily). While there were no unexpected toxicities, no patients experienced an objective response, though one had stable disease lasting 16 months. We conclude that in spite of pre-clinical activity and anecdotal cases of response to EGFR inhibitors, routine use of the EGFR inhibitor gefitinib as a single agent for advanced AML is not appropriate.
需要新的疗法来治疗急性髓系白血病，以克服疾病的耐药性，并为老年患者提供潜在毒性更小的治疗方法。先前涉及非小细胞肺癌患者的临床试验已经证明了在精心挑选的患者中使用 EGFR 抑制剂的安全性和生物学活性。这种方法在急性髓系白血病患者中的潜在疗效尚不清楚。吉非替尼对 AML 细胞系和原发性患者 AML 细胞的分化诱导和细胞活力的影响先前已有报道，并且在临床可达到的范围内抑制了细胞活力。为了确定 EGFR 抑制剂在晚期 AML 中的治疗效果是否有效，我们进行了一项 II 期临床试验，其中 18 名中位年龄为 72 岁（范围为 57-84 岁）的患者接受了吉非替尼（每天口服 750mg）治疗。虽然没有出现意外的毒性反应，但没有患者出现客观缓解，尽管有 1 例患者的疾病稳定持续了 16 个月。我们的结论是，尽管有临床前活性和 EGFR 抑制剂反应的病例报告，但常规使用 EGFR 抑制剂吉非替尼作为晚期 AML 的单一药物是不合适的。
