Acute aortic dissection during axitinib therapy
561
Acute aortic dissection in a patient with metastatic renal cell carcinoma treated with axitinib
NAOYA NIWA, TORU NISHIYAMA, CHOICHIRO OZU, YASUTO YAGI & SHIRO SAITO National Hospital Organization Tokyo Medical Center, Department of Urology, Tokyo, Japan
Acta Oncol 2015.54:561-562. Downloaded from informahealthcare.com by Kainan University on 04/09/15. For personal use only.
To the Editor, Axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3, and has been approved for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy. Compared with first-generation tyrosine kinase inhibitors (TKIs), such as sorafenib, axitinib is a more specific VEGFR inhibitor. The toxicity profile of axitinib is tolerable. Common adverse events of axitinib include diarrhea, hypertension, and fatigue, and they have also been reported after using other TKIs. Other adverse events, such as palmar-plantar erythrodysesthesia, cutaneous toxicity, and myelosuppression, are less commonly reported after using axitinib than after using other TKIs [1]. A 51-year-old man with a renal tumor, but without any other comorbidities including hypertension, underwent left radical nephrectomy. Pathological examination revealed the tumor as a pT3aN0M0 clear cell renal cell carcinoma. Six months after surgery, multiple lung metastases were detected via thoracic computed tomography (CT), after which sunitinib was administered as a four-weeks-on and two-weeks-off schedule. Sunitinib was discontinued owing to grade 3 palmar-plantar erythrodysesthesia after two cycles of treatment, and the patient was switched to axitinib. Ten days after receiving axitinib, he presented to the urology outpatient department with sudden midsternal pain. He looked well, and his blood pressure was 127/66 mmHg. An electrocardiogram showed ST-segment elevation in all leads. Contrast-enhanced thoracoabdominal CT revealed acute aortic dissection (Stanford type A) from the ascending aorta to the left external iliac artery (Figure 1). The patient underwent emergency reconstruction of the ascending aorta. Acute aortic dissection is a life-threatening entity. The most common predisposing factor is hypertension, followed by atherosclerosis, history of cardiac
surgery, Marfan syndrome, and iatrogenic causes [2]. Hypertension is a frequent adverse event with axitinib and other small-molecule TKIs. Other cardiovascular toxicities including heart failure, left ventricular systolic dysfunction, and QT prolongation have also been reported. The mechanism of TKIassociated cardiotoxicity remains poorly understood. Possible mechanisms include the loss of vascular stability because of endothelial cell damage or decreased production of nitric oxide through inhibition of VEGF pathways [3]. To our knowledge, this is the first case of acute aortic dissection in a patient treated with axitinib. Only two cases of aortic dissection during treatment with small-molecule multitargeted TKIs (1 with sorafenib [4] and 1 with sunitinib [5]) were
Figure 1. Sagittal reconstruction of a contrast-enhanced computed tomography scan showing an aortic dissection involving the ascending aorta (arrowheads).
Correspondence: N. Niwa, Department of Urology, National Hospital Organization Tokyo Medical Center, 2-5-1, Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan. E-mail: [email protected] (Received 21 August 2014 ; accepted 3 September 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.963887
Acta Oncol 2015.54:561-562. Downloaded from informahealthcare.com by Kainan University on 04/09/15. For personal use only.
562
J. V. Brower et al.
previously published. Preexisting or drug-induced hypertension was observed in both cases. In this case, high blood pressure had not been observed before or during small-molecule multitargeted TKI therapy. We suspected in this case aortic dissection is associated with axitinib, because he had no predisposing factor of aortic dissection including hypertension and it occurred soon after the initiation of axitinib. However, the causality between axitinib and acute aortic dissection could not be completely established in this case and further clinical observation is required. Axitinib has a relatively short history since its official approval, and its mechanism of action is not yet understood fully. Therefore, clinicians should be aware of this life threatening complication associated with using axitinib and other TKIs.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised phase 3 trial. Lancet 2011;378:1931–9. [2] Sheikh AS, Ali K, Mazhar S. Acute aortic syndrome. Circulation 2013;128:1122–7. [3] Lenihan DJ, Kowey PR. Overview and management of cardiac adverse events associated with tyrosine kinase inhibitors. Oncologist 2013;18:900–8. [4] Serrano C, Suarez C, Andreu J, Carles J. Acute aortic dissection during sorafenib-containing therapy. Ann Oncol 2010;21:181–2. [5] Edeline J, Laguerre B, Rolland Y, Patard JJ. Aortic dissection in a patient treated by sunitinib for metastatic renal cell carcinoma. Ann Oncol 2010;21:186–7.
Proton therapy and helical tomotherapy result in reduced dose deposition to the pancreas in the setting of cranio-spinal irradiation for medulloblastoma: Implications for reduced risk of diabetes mellitus in long-term survivors
JEFFREY V. BROWER1,2, SHAE GANS1, WILLIAM F. HARTSELL1, STEWART GOLDMAN1,3, JASON R. FANGUSARO1,3, NEHA PATEL4, RISHI R. LULLA1,3, NATASHA PILLAY SMILEY1,3, JOHN HAN-CHIH CHANG1 & VINAI GONDI1,2 1CDH
Proton Center, Warrenville, Illinois, USA, 2University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA, 3Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA and 4Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison, Wisconsin, USA Many pediatric cancer patients require cranio-spinal irradiation (CSI) as part of curative treatment for various childhood central nervous system malignancies. Notably, medulloblastoma represents the most common malignant pediatric brain tumor requiring CSI. Aggressive treatment regimens in this setting result in relatively high cure rates, with five-year overall survival (OS) ranging from 72% to 85% [1]. As a result of long-term survival following comprehensive treatment, many patients are at risk for the development of late effects [2]. Standard photon beam irradiation of the craniospinal axis has been associated with late effects to include vertebral growth arrest, cardiac dysfunction,
restrictive lung disease and gonadal dysfunction [3]. Furthermore, pediatric patients receiving central nervous system (CNS) irradiation may be subject to a number of well-characterized treatment-related late effects to include neurocognitive deficits, endocrine dysfunction, secondary malignancy and hearing deficits [4]. The capacity for increased target conformality of proton beam therapy (PBT) has been proposed to reduce late effects, with ongoing investigation into clinical outcomes [5,6]. Accumulating evidence from the literature demonstrates a linkage between the development of diabetes mellitus (DM) and total body/abdominal irradiation [7,8]. A recent multi-institution study, by deVathaire
Correspondence: J. Brower, University of Wisconsin Hospital and Clinics, 600 Highland Avenue, K4/B100, Madison, WI 53792, USA. Tel: ⫹ 1 608 263-8500; Fax: ⫹ 1 608 263-9167. E-mail: [email protected] (Received 7 September 2014 ; accepted 13 October 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.978368
561
Acute aortic dissection in a patient with metastatic renal cell carcinoma treated with axitinib
NAOYA NIWA, TORU NISHIYAMA, CHOICHIRO OZU, YASUTO YAGI & SHIRO SAITO National Hospital Organization Tokyo Medical Center, Department of Urology, Tokyo, Japan
Acta Oncol 2015.54:561-562. Downloaded from informahealthcare.com by Kainan University on 04/09/15. For personal use only.
To the Editor, Axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3, and has been approved for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy. Compared with first-generation tyrosine kinase inhibitors (TKIs), such as sorafenib, axitinib is a more specific VEGFR inhibitor. The toxicity profile of axitinib is tolerable. Common adverse events of axitinib include diarrhea, hypertension, and fatigue, and they have also been reported after using other TKIs. Other adverse events, such as palmar-plantar erythrodysesthesia, cutaneous toxicity, and myelosuppression, are less commonly reported after using axitinib than after using other TKIs [1]. A 51-year-old man with a renal tumor, but without any other comorbidities including hypertension, underwent left radical nephrectomy. Pathological examination revealed the tumor as a pT3aN0M0 clear cell renal cell carcinoma. Six months after surgery, multiple lung metastases were detected via thoracic computed tomography (CT), after which sunitinib was administered as a four-weeks-on and two-weeks-off schedule. Sunitinib was discontinued owing to grade 3 palmar-plantar erythrodysesthesia after two cycles of treatment, and the patient was switched to axitinib. Ten days after receiving axitinib, he presented to the urology outpatient department with sudden midsternal pain. He looked well, and his blood pressure was 127/66 mmHg. An electrocardiogram showed ST-segment elevation in all leads. Contrast-enhanced thoracoabdominal CT revealed acute aortic dissection (Stanford type A) from the ascending aorta to the left external iliac artery (Figure 1). The patient underwent emergency reconstruction of the ascending aorta. Acute aortic dissection is a life-threatening entity. The most common predisposing factor is hypertension, followed by atherosclerosis, history of cardiac
surgery, Marfan syndrome, and iatrogenic causes [2]. Hypertension is a frequent adverse event with axitinib and other small-molecule TKIs. Other cardiovascular toxicities including heart failure, left ventricular systolic dysfunction, and QT prolongation have also been reported. The mechanism of TKIassociated cardiotoxicity remains poorly understood. Possible mechanisms include the loss of vascular stability because of endothelial cell damage or decreased production of nitric oxide through inhibition of VEGF pathways [3]. To our knowledge, this is the first case of acute aortic dissection in a patient treated with axitinib. Only two cases of aortic dissection during treatment with small-molecule multitargeted TKIs (1 with sorafenib [4] and 1 with sunitinib [5]) were
Figure 1. Sagittal reconstruction of a contrast-enhanced computed tomography scan showing an aortic dissection involving the ascending aorta (arrowheads).
Correspondence: N. Niwa, Department of Urology, National Hospital Organization Tokyo Medical Center, 2-5-1, Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan. E-mail: [email protected] (Received 21 August 2014 ; accepted 3 September 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.963887
Acta Oncol 2015.54:561-562. Downloaded from informahealthcare.com by Kainan University on 04/09/15. For personal use only.
562
J. V. Brower et al.
previously published. Preexisting or drug-induced hypertension was observed in both cases. In this case, high blood pressure had not been observed before or during small-molecule multitargeted TKI therapy. We suspected in this case aortic dissection is associated with axitinib, because he had no predisposing factor of aortic dissection including hypertension and it occurred soon after the initiation of axitinib. However, the causality between axitinib and acute aortic dissection could not be completely established in this case and further clinical observation is required. Axitinib has a relatively short history since its official approval, and its mechanism of action is not yet understood fully. Therefore, clinicians should be aware of this life threatening complication associated with using axitinib and other TKIs.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised phase 3 trial. Lancet 2011;378:1931–9. [2] Sheikh AS, Ali K, Mazhar S. Acute aortic syndrome. Circulation 2013;128:1122–7. [3] Lenihan DJ, Kowey PR. Overview and management of cardiac adverse events associated with tyrosine kinase inhibitors. Oncologist 2013;18:900–8. [4] Serrano C, Suarez C, Andreu J, Carles J. Acute aortic dissection during sorafenib-containing therapy. Ann Oncol 2010;21:181–2. [5] Edeline J, Laguerre B, Rolland Y, Patard JJ. Aortic dissection in a patient treated by sunitinib for metastatic renal cell carcinoma. Ann Oncol 2010;21:186–7.
Proton therapy and helical tomotherapy result in reduced dose deposition to the pancreas in the setting of cranio-spinal irradiation for medulloblastoma: Implications for reduced risk of diabetes mellitus in long-term survivors
JEFFREY V. BROWER1,2, SHAE GANS1, WILLIAM F. HARTSELL1, STEWART GOLDMAN1,3, JASON R. FANGUSARO1,3, NEHA PATEL4, RISHI R. LULLA1,3, NATASHA PILLAY SMILEY1,3, JOHN HAN-CHIH CHANG1 & VINAI GONDI1,2 1CDH
Proton Center, Warrenville, Illinois, USA, 2University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA, 3Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA and 4Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison, Wisconsin, USA Many pediatric cancer patients require cranio-spinal irradiation (CSI) as part of curative treatment for various childhood central nervous system malignancies. Notably, medulloblastoma represents the most common malignant pediatric brain tumor requiring CSI. Aggressive treatment regimens in this setting result in relatively high cure rates, with five-year overall survival (OS) ranging from 72% to 85% [1]. As a result of long-term survival following comprehensive treatment, many patients are at risk for the development of late effects [2]. Standard photon beam irradiation of the craniospinal axis has been associated with late effects to include vertebral growth arrest, cardiac dysfunction,
restrictive lung disease and gonadal dysfunction [3]. Furthermore, pediatric patients receiving central nervous system (CNS) irradiation may be subject to a number of well-characterized treatment-related late effects to include neurocognitive deficits, endocrine dysfunction, secondary malignancy and hearing deficits [4]. The capacity for increased target conformality of proton beam therapy (PBT) has been proposed to reduce late effects, with ongoing investigation into clinical outcomes [5,6]. Accumulating evidence from the literature demonstrates a linkage between the development of diabetes mellitus (DM) and total body/abdominal irradiation [7,8]. A recent multi-institution study, by deVathaire
Correspondence: J. Brower, University of Wisconsin Hospital and Clinics, 600 Highland Avenue, K4/B100, Madison, WI 53792, USA. Tel: ⫹ 1 608 263-8500; Fax: ⫹ 1 608 263-9167. E-mail: [email protected] (Received 7 September 2014 ; accepted 13 October 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.978368
