To the Editor: Gefitinib is an orally active inhibitor of tyrosinekinase epidermal growth factor,1 with clinical effectivenessin the control of non–small-cell lung cancer. We describe3 patients with possible treatment-related acute promyelocyticleukemia (APL) among 108 consecutive patients with advanced,recurrent non–small-cell lung cancer who were treatedwith gefitinib between November 2001 and December 2004 at ourinstitution (Table 1). Other than these three patients, no patientswith other cancers have been identified in this cohort.
Table 1. Characteristics of Three Patients with APL during Treatment with Gefitinib for Recurrence of Non–Small-Cell Lung Cancer.
Chemotherapy, including the use of topoisomerase II inhibitors(e.g., anthracyclines), and radiotherapy are known as predisposingfactors for treatment-related APL,2 and all our patients hadbeen exposed to cytotoxic agents as well as radiation beforethe initiation of gefitinib therapy. Therefore, it is difficultto identify gefitinib as the sole cause of the treatment-relatedAPL. However, the incidence of this complication in our gefitinib-treatedcohort is far beyond that expected on the basis of our clinicalexperience of treatment for non–small-cell lung cancerbefore gefitinib was commercially available. Considering that3 percent of treatment-related acute myeloid leukemias are APL,3the cluster of treatment-related APL in our cohort suggeststhat gefitinib, alone or in combination with other environmentalfactors, such as cytotoxic drugs or radiotherapy, is a riskfactor for APL. We believe that further evaluation in a large-scaleepidemiologic study is required to elucidate the associationbetween gefitinib and treatment-related APL.
Akiko Uchida, M.D. Okayama University Graduate School of Medicine and Dentistry Okayama 700-8558, Japan
Keitaro Matsuo, M.D., Ph.D. Aichi Cancer Center Research Institute Nagoya 464-8681, Japan
Mitsune Tanimoto, M.D., Ph.D. Okayama University GraduateSchool of Medicine and Dentistry Okayama 700-8558, Japan
References
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Beaumont M, Sanz M, Carli PM, et al. Therapy-related acute promyelocytic leukemia. J Clin Oncol 2003;21:2123-2137. [Free Full Text]
Mauritzson N, Albin M, Rylander L, et al. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001. Leukemia 2002;16:2366-2378. [CrossRef][Web of Science][Medline]
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