APL during Gefitinib Treatment for Non–Small-Cell Lung Cancer
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《新英格兰医药杂志》
To the Editor: Gefitinib is an orally active inhibitor of tyrosine kinase epidermal growth factor,1 with clinical effectiveness in the control of non–small-cell lung cancer. We describe 3 patients with possible treatment-related acute promyelocytic leukemia (APL) among 108 consecutive patients with advanced, recurrent non–small-cell lung cancer who were treated with gefitinib between November 2001 and December 2004 at our institution (Table 1). Other than these three patients, no patients with 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 predisposing factors for treatment-related APL,2 and all our patients had been exposed to cytotoxic agents as well as radiation before the initiation of gefitinib therapy. Therefore, it is difficult to identify gefitinib as the sole cause of the treatment-related APL. However, the incidence of this complication in our gefitinib-treated cohort is far beyond that expected on the basis of our clinical experience of treatment for non–small-cell lung cancer before gefitinib was commercially available. Considering that 3 percent of treatment-related acute myeloid leukemias are APL,3 the cluster of treatment-related APL in our cohort suggests that gefitinib, alone or in combination with other environmental factors, such as cytotoxic drugs or radiotherapy, is a risk factor for APL. We believe that further evaluation in a large-scale epidemiologic study is required to elucidate the association between 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 Graduate School of Medicine and Dentistry
Okayama 700-8558, Japan
References
Lawrence DS, Niu J. Protein kinase inhibitors: the tyrosine-specific protein kinases. Pharmacol Ther 1998;77:81-114.
Beaumont M, Sanz M, Carli PM, et al. Therapy-related acute promyelocytic leukemia. J Clin Oncol 2003;21:2123-2137.
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.
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 predisposing factors for treatment-related APL,2 and all our patients had been exposed to cytotoxic agents as well as radiation before the initiation of gefitinib therapy. Therefore, it is difficult to identify gefitinib as the sole cause of the treatment-related APL. However, the incidence of this complication in our gefitinib-treated cohort is far beyond that expected on the basis of our clinical experience of treatment for non–small-cell lung cancer before gefitinib was commercially available. Considering that 3 percent of treatment-related acute myeloid leukemias are APL,3 the cluster of treatment-related APL in our cohort suggests that gefitinib, alone or in combination with other environmental factors, such as cytotoxic drugs or radiotherapy, is a risk factor for APL. We believe that further evaluation in a large-scale epidemiologic study is required to elucidate the association between 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 Graduate School of Medicine and Dentistry
Okayama 700-8558, Japan
References
Lawrence DS, Niu J. Protein kinase inhibitors: the tyrosine-specific protein kinases. Pharmacol Ther 1998;77:81-114.
Beaumont M, Sanz M, Carli PM, et al. Therapy-related acute promyelocytic leukemia. J Clin Oncol 2003;21:2123-2137.
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.