Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer

Experience at a single institution

Keitaro Matsuo, Katsuyuki Kiura, Masahiro Tabata, Akiko Uchida, Katsuyuki Hotta, Daigo Niiya, Shiro Kubonishi, Atsuko Ogino, Yoshiro Fujiwara, Hiromi Nakajima, Katsuji Shinagawa, Fumihiko Ishimaru, Hiroshi Ueoka, Mitsune Tanimoto

Research output: Contribution to journalArticle

7 Citations (Scopus)

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-RARα 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.

Original languageEnglish
Pages (from-to)349-354
Number of pages6
JournalAmerican Journal of Hematology
Volume81
Issue number5
DOIs
Publication statusPublished - May 2006

Fingerprint

Acute Promyelocytic Leukemia
Non-Small Cell Lung Carcinoma
Incidence
Leukemia
Therapeutics
Confidence Intervals
Poisson Distribution
Disseminated Intravascular Coagulation
Cytotoxins
Tretinoin
Karyotype
Epidermal Growth Factor Receptor
Thrombocytopenia
Protein-Tyrosine Kinases
Population
gefitinib
Japan
Radiotherapy
Polymerase Chain Reaction
Neoplasms

Keywords

  • Acute promyelocytic leukemia
  • Gefitinib
  • Non-small-cell lung cancer
  • Second malignancy

ASJC Scopus subject areas

  • Hematology

Cite this

Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer : Experience at a single institution. / 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.

In: American Journal of Hematology, Vol. 81, No. 5, 05.2006, p. 349-354.

Research output: Contribution to journalArticle

Matsuo, K, Kiura, K, Tabata, M, Uchida, A, Hotta, K, Niiya, D, Kubonishi, S, Ogino, A, Fujiwara, Y, Nakajima, H, Shinagawa, K, Ishimaru, F, Ueoka, H & Tanimoto, M 2006, 'Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer: Experience at a single institution', American Journal of Hematology, vol. 81, no. 5, pp. 349-354. https://doi.org/10.1002/ajh.20569
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. / Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer : Experience at a single institution. In: American Journal of Hematology. 2006 ; Vol. 81, No. 5. pp. 349-354.
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