- Email: [email protected]
Thymic Small Cell Carcinoma Shows Marked Response to Amrubicin
Journal of Thoracic Oncology • Volume 4, Number 6, June 2009
Letters to the Editor
necessary to refine the diagnostic criteria of both entities. Robert Kridel, MD Division of Oncology Department of Internal Medicine Geneva University Hospitals Geneva, Switzerland [email protected]
Jean-Claude Pache, MD Department of Medical Genetics and Laboratories Geneva University Hospitals Geneva, Switzerland
FIGURE 1. A, Computed tomography before administration of AMR. B, Marked diminution in size of the mass in the anterior mediastinum.
REFERENCES 1. von Herbay A, Illes A, Waldherr R, Otto HF. Pulmonary tumor thrombotic microangiopathy with pulmonary hypertension. Cancer 1990;66:587–592. 2. Winterbauer RH, Elfenbein IB, Ball WC Jr. Incidence and clinical significance of tumor embolization to the lungs. Am J Med 1968;45: 271–290. 3. Kridel R, Myit S, Pache JC, Gaspoz JM. Pulmonary tumor embolism: a rare cause of acute right heart failure with elevated Ddimers. J Thorac Oncol 2008;3:1482–1483. 4. Kane RD, Hawkins HK, Miller JA, Noce PS. Microscopic pulmonary tumor emboli associated with dyspnea. Cancer 1975;36:1473– 1482. 5. Bassiri AG, Haghighi B, Doyle RL, Berry GJ, Rizk NW. Pulmonary tumor embolism. Am J Respir Crit Care Med 1997;155: 2089 –2095. 6. Roberts KE, Hamele-Bena D, Saqi A, Stein CA, Cole RP. Pulmonary tumor embolism: a review of the literature. Am J Med 2003;115:228 –232.
Thymic Small Cell Carcinoma Shows Marked Response to Amrubicin To the Editor: Thymic small cell carcinoma (small cell carcinoma, neuroendocrine type according to the World Health Organization histologic classification) is a rare aggressive mediastinal neoplasm, and the optimal treatment remains undefined. In this report, we describe a case of thymic small cell carcinoma that showed marked response to second-line Disclosure: The authors declare no conflicts of interest. Copyright © 2009 by the International Association for the Study of Lung Cancer ISSN: /09/0406-0778
778
1200.0
CBDCA+paclitaxel
AMR
1000.0
800.0
600.0
400.0
200.0
0.0
NSE
PROGRP
CBDCA , Carboplatin ; AMR, amrubicin ; NSE, neuron specific enolase (ng/ml); ProGRP; pro-gastrin releasing peptide (pg/ml)
FIGURE 2. Clinical course and serum levels of neuron specific enolase (NSE) and progastrin-releasing peptide (ProGRP).
chemotherapy with single-agent amrubicin (AMR), a synthetic anthracycline analogue and potent deoxyribonucleic acid topoisomerase II inhibitor. A 57-year-old man was diagnosed to have thymic small cell carcinoma with pericardial sac invasion, pleural dissemination and pulmonary metastasis (stage IVb according to the classification proposed by Masaoka et al). The patient was initially treated by combination chemotherapy with paclitaxel and carboplatin, in September 2006. Four cycles of the chemotherapy were administered, and partial response was confirmed. However, regrowth of the mass in the anterior mediastinum and that of the pulmonary metastasis were observed (Figure 1A). In addition, the serum levels of neuron-specific enolase (80 ng/ ml) and progastrin-releasing peptide (ProGRP, 515 ng/ml) were also elevated (Figure 2). For the treatment in the second-line setting, AMR administration
was begun in May 2007 at the dose of 40 mg/m2/d on days 1 to 3, every 3 weeks. A chest computed tomography after four cycles of AMR treatment demonstrated a marked reduction in the size of the anterior mediastinal mass and that of the pulmonary metastasis, confirming partial response (Figure 1B). Both the serum neuron-specific enolase and ProGRP levels decreased to their respective normal ranges (Figure 2). The adverse events related to AMR were no higher than grade 1 in severity, according to the Common Toxicity Criteria for Adverse Events, Version 3.0 grading system, proposed by the National Cancer Institute. Only grade 1 neutropenia and leukopenia were observed. After seven cycles of AMR treatment, the chest computed tomography obtained in January 2008 revealed regrowth of the anterior mediastinal mass and the serum level of ProGRP was also elevated. Although, subsequent treatments
Copyright © 2009 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology • Volume 4, Number 6, June 2009
(third-line chemotherapy with gemcitabine, fourth-line therapy with irinotecan, and fifth-line therapy with a combination of carboplatin and paclitaxel) were administered with disease progression, no responses to these treatments were observed, and the patient died in November 2008. Several reports have indicated the efficacy of combination regimens containing cisplatin and doxorubicin, such as Cisplatin ⫹ Doxorubicin ⫹ Vincristine ⫹ Cyclophosphamide and Cisplatin ⫹ Vincristine ⫹ Doxorubicin ⫹ Etoposide, against thymic carcinoma.1,2 Consequently, doxorubicin has been considered as highly reliable agent against thymic carcinoma. AMR is a totally synthetic anthracycline, and has been demonstrated to have equivalent or stronger antitumor effect as compared with doxorubicin in an experimental animal model.3 Phase II
studies with single-agent AMR in previously treated extensive small cell lung cancer have shown variable clinical responses and survivals.4,5 Thus, it might be reasonable to suppose that AMR, an anthracycline, is not only a reliable agent against thymic carcinoma, but also against thymic small cell carcinoma. To our knowledge, this is the first report to suggest the activity of AMR against advanced thymic small cell carcinoma in the second-line setting. AMR can be an active agent against advanced thymic small cell carcinoma. Satoshi Igawa, MD, PhD Haruyasu Murakami, MD, PhD Nobuyuki Yamamoto, MD, PhD Divisions of Thoracic Oncology Shizuoka Cancer Center Nagaizumi Shizuoka, Japan [email protected]
Copyright © 2009 by the International Association for the Study of Lung Cancer
Letters to the Editor
REFERENCES 1. Koizumi T, Takabayashi Y, Yamagishi S, et al. Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol 2002;25:266 –268. 2. Yoh K, Goto K, Ishii G, et al. Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide is an effective treatment for advanced thymic carcinoma. Cancer 2003; 98:926 –931. 3. Yamaoka T, Hanada M, Ichii S, Morisada S, Noguchi T, Yanagi Y. Cytotoxicity of amrubicin, a novel 9-aminoanthracycline, and its active metabolite amrubicinol on human tumor cells. Jpn J Cancer Res. 1998;89:1067– 1073. 4. Onoda S, Masuda N, Seto T, et al; Thoracic Oncology Research Group Study 030. Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 2006;24:5448 –5453. 5. Kato T, Nokihara H, Ohe Y, et al. Phase II trial amrubicin in patients with previously treated small cell lung cancer (SCLC). J Clin Oncol 2006;24(Suppl):7061.
779
Letters to the Editor
necessary to refine the diagnostic criteria of both entities. Robert Kridel, MD Division of Oncology Department of Internal Medicine Geneva University Hospitals Geneva, Switzerland [email protected]
Jean-Claude Pache, MD Department of Medical Genetics and Laboratories Geneva University Hospitals Geneva, Switzerland
FIGURE 1. A, Computed tomography before administration of AMR. B, Marked diminution in size of the mass in the anterior mediastinum.
REFERENCES 1. von Herbay A, Illes A, Waldherr R, Otto HF. Pulmonary tumor thrombotic microangiopathy with pulmonary hypertension. Cancer 1990;66:587–592. 2. Winterbauer RH, Elfenbein IB, Ball WC Jr. Incidence and clinical significance of tumor embolization to the lungs. Am J Med 1968;45: 271–290. 3. Kridel R, Myit S, Pache JC, Gaspoz JM. Pulmonary tumor embolism: a rare cause of acute right heart failure with elevated Ddimers. J Thorac Oncol 2008;3:1482–1483. 4. Kane RD, Hawkins HK, Miller JA, Noce PS. Microscopic pulmonary tumor emboli associated with dyspnea. Cancer 1975;36:1473– 1482. 5. Bassiri AG, Haghighi B, Doyle RL, Berry GJ, Rizk NW. Pulmonary tumor embolism. Am J Respir Crit Care Med 1997;155: 2089 –2095. 6. Roberts KE, Hamele-Bena D, Saqi A, Stein CA, Cole RP. Pulmonary tumor embolism: a review of the literature. Am J Med 2003;115:228 –232.
Thymic Small Cell Carcinoma Shows Marked Response to Amrubicin To the Editor: Thymic small cell carcinoma (small cell carcinoma, neuroendocrine type according to the World Health Organization histologic classification) is a rare aggressive mediastinal neoplasm, and the optimal treatment remains undefined. In this report, we describe a case of thymic small cell carcinoma that showed marked response to second-line Disclosure: The authors declare no conflicts of interest. Copyright © 2009 by the International Association for the Study of Lung Cancer ISSN: /09/0406-0778
778
1200.0
CBDCA+paclitaxel
AMR
1000.0
800.0
600.0
400.0
200.0
0.0
NSE
PROGRP
CBDCA , Carboplatin ; AMR, amrubicin ; NSE, neuron specific enolase (ng/ml); ProGRP; pro-gastrin releasing peptide (pg/ml)
FIGURE 2. Clinical course and serum levels of neuron specific enolase (NSE) and progastrin-releasing peptide (ProGRP).
chemotherapy with single-agent amrubicin (AMR), a synthetic anthracycline analogue and potent deoxyribonucleic acid topoisomerase II inhibitor. A 57-year-old man was diagnosed to have thymic small cell carcinoma with pericardial sac invasion, pleural dissemination and pulmonary metastasis (stage IVb according to the classification proposed by Masaoka et al). The patient was initially treated by combination chemotherapy with paclitaxel and carboplatin, in September 2006. Four cycles of the chemotherapy were administered, and partial response was confirmed. However, regrowth of the mass in the anterior mediastinum and that of the pulmonary metastasis were observed (Figure 1A). In addition, the serum levels of neuron-specific enolase (80 ng/ ml) and progastrin-releasing peptide (ProGRP, 515 ng/ml) were also elevated (Figure 2). For the treatment in the second-line setting, AMR administration
was begun in May 2007 at the dose of 40 mg/m2/d on days 1 to 3, every 3 weeks. A chest computed tomography after four cycles of AMR treatment demonstrated a marked reduction in the size of the anterior mediastinal mass and that of the pulmonary metastasis, confirming partial response (Figure 1B). Both the serum neuron-specific enolase and ProGRP levels decreased to their respective normal ranges (Figure 2). The adverse events related to AMR were no higher than grade 1 in severity, according to the Common Toxicity Criteria for Adverse Events, Version 3.0 grading system, proposed by the National Cancer Institute. Only grade 1 neutropenia and leukopenia were observed. After seven cycles of AMR treatment, the chest computed tomography obtained in January 2008 revealed regrowth of the anterior mediastinal mass and the serum level of ProGRP was also elevated. Although, subsequent treatments
Copyright © 2009 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology • Volume 4, Number 6, June 2009
(third-line chemotherapy with gemcitabine, fourth-line therapy with irinotecan, and fifth-line therapy with a combination of carboplatin and paclitaxel) were administered with disease progression, no responses to these treatments were observed, and the patient died in November 2008. Several reports have indicated the efficacy of combination regimens containing cisplatin and doxorubicin, such as Cisplatin ⫹ Doxorubicin ⫹ Vincristine ⫹ Cyclophosphamide and Cisplatin ⫹ Vincristine ⫹ Doxorubicin ⫹ Etoposide, against thymic carcinoma.1,2 Consequently, doxorubicin has been considered as highly reliable agent against thymic carcinoma. AMR is a totally synthetic anthracycline, and has been demonstrated to have equivalent or stronger antitumor effect as compared with doxorubicin in an experimental animal model.3 Phase II
studies with single-agent AMR in previously treated extensive small cell lung cancer have shown variable clinical responses and survivals.4,5 Thus, it might be reasonable to suppose that AMR, an anthracycline, is not only a reliable agent against thymic carcinoma, but also against thymic small cell carcinoma. To our knowledge, this is the first report to suggest the activity of AMR against advanced thymic small cell carcinoma in the second-line setting. AMR can be an active agent against advanced thymic small cell carcinoma. Satoshi Igawa, MD, PhD Haruyasu Murakami, MD, PhD Nobuyuki Yamamoto, MD, PhD Divisions of Thoracic Oncology Shizuoka Cancer Center Nagaizumi Shizuoka, Japan [email protected]
Copyright © 2009 by the International Association for the Study of Lung Cancer
Letters to the Editor
REFERENCES 1. Koizumi T, Takabayashi Y, Yamagishi S, et al. Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol 2002;25:266 –268. 2. Yoh K, Goto K, Ishii G, et al. Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide is an effective treatment for advanced thymic carcinoma. Cancer 2003; 98:926 –931. 3. Yamaoka T, Hanada M, Ichii S, Morisada S, Noguchi T, Yanagi Y. Cytotoxicity of amrubicin, a novel 9-aminoanthracycline, and its active metabolite amrubicinol on human tumor cells. Jpn J Cancer Res. 1998;89:1067– 1073. 4. Onoda S, Masuda N, Seto T, et al; Thoracic Oncology Research Group Study 030. Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 2006;24:5448 –5453. 5. Kato T, Nokihara H, Ohe Y, et al. Phase II trial amrubicin in patients with previously treated small cell lung cancer (SCLC). J Clin Oncol 2006;24(Suppl):7061.
779