Matsuo Keitaro, Kiura Katsuyuki, Tabata Masahiro, Uchida Akiko, Hotta Katsuyuki, Niiya Daigo, Kubonishi Shiro, Ogino Atsuko, Fujiwara Yoshiro, Nakajima Hiromi, Shinagawa Katsuji, Ishimaru Fumihiko, Ueoka Hiroshi, Tanimoto Mitsune
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Am J Hematol. 2006 May;81(5):349-54. doi: 10.1002/ajh.20569.
Although gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been shown a significant activity for recurrent non-small-cell lung cancer (NSCLC), its long-term adverse effect with its continuous usage has hitherto not been clearly elucidated. Subjects were 108 consecutive NSCLC cases who were treated with gefitinib between November 2001 and December 2004 at our single institution. A crude incidence rate ratio was calculated by ratio of crude incidence rate in our subject to population-based incident rate of all leukemia (ICD: C91-95) in the same region. The 95% confidence intervals (CIs) were calculated based upon a Poisson distribution. Three cases of acute promyelocytic leukemia (APL) occurred during gefitinib treatment, and these patients' past treatment histories are presented herein. No other malignancy was identified. All of the cases were diagnosed at the stage of mild-to-moderate cytopenia, especially thrombocytopenia, without disseminated intravascular coagulation. All presented a normal karyotype with positive PML-RARalpha in RT-PCR, indicating submicroscopic translocation. They responded well to APL treatments, including all-trans-retinoic acid. The crude incident rate ratio was 639.9 (95% confidence interval: 131.6-1,878.9, P < 0.0001) when the APL incidence in this cohort was compared to all leukemia cases in the general population in the same district in Japan. Thus we had three cases of secondary APL patients within the gefitinib-treated NSCLC cohort. Although we cannot exclude an effect of past exposure of other cytotoxic agents and radiotherapy as a cause of APL, APL inducibility of gefitinib should be clarified in the further study.
尽管表皮生长因子受体酪氨酸激酶抑制剂吉非替尼已被证明对复发性非小细胞肺癌（NSCLC）具有显著活性，但其长期持续使用的不良反应迄今尚未明确阐明。研究对象为2001年11月至2004年12月在我们单中心接受吉非替尼治疗的108例连续NSCLC患者。通过计算本研究对象的粗发病率与同一地区基于人群的所有白血病（ICD：C91 - 95）发病率之比，得出粗发病率比。基于泊松分布计算95%置信区间（CI）。在吉非替尼治疗期间发生了3例急性早幼粒细胞白血病（APL），本文介绍了这些患者既往的治疗史。未发现其他恶性肿瘤。所有病例均在轻度至中度血细胞减少阶段被诊断，尤其是血小板减少，无弥散性血管内凝血。所有病例核型正常，RT - PCR检测PML - RARα呈阳性，提示亚显微易位。他们对包括全反式维甲酸在内的APL治疗反应良好。当将该队列中的APL发病率与日本同一地区普通人群中的所有白血病病例进行比较时，粗发病率比为639.9（95%置信区间：131.6 - 1,878.9，P < 0.0001）。因此，在接受吉非替尼治疗的NSCLC队列中有3例继发性APL患者。尽管我们不能排除既往接触其他细胞毒性药物和放疗作为APL病因的影响，但吉非替尼诱导APL的可能性应在进一步研究中阐明。
