title: Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer: experience at a single institution.
abstract: 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.
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. kmatsuo@aichi-cc.jp
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Akiko
authors.initials: A
authors.lastname: Uchida
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Daigo
authors.initials: D
authors.lastname: Niiya
authors.forename: Shiro
authors.initials: S
authors.lastname: Kubonishi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ogino
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakajima
authors.forename: Katsuji
authors.initials: K
authors.lastname: Shinagawa
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishimaru
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy*; D016000:Cluster Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015994:Incidence; D015473:Leukemia, Promyelocytic, Acute / Q000139:chemically induced / Q000453:epidemiology; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib