Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Angiosarcoma of the Retroperitoneum: Report on a Patient Treated with Sunitinib

Angiosarcoma of the Retroperitoneum: Report on a Patient Treated with Sunitinib Hindawi Publishing Corporation Sarcoma Volume 2009, Article ID 360875, 4 pages doi:10.1155/2009/360875 Case Report Angiosarcomaofthe Retroperitoneum: Report on a Patient Treated with Sunitinib 1 1 1 2 3 Changhoon Yoo, Jeong-Eun Kim, Shin-Kyo Yoon, Song Cheol Kim, Jin-Hee Ahn, 3 3 3 Tae Won Kim, Cheolwon Suh, and Jae-Lyun Lee Department of Internal medicine, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736, South Korea Department of Surgery, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736, South Korea Department of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736, South Korea Correspondence should be addressed to Jae-Lyun Lee, jaelyun@amc.seoul.kr Received 13 January 2009; Accepted 20 April 2009 Recommended by Cyril Fisher A 52 year-old woman presented with an incidentally detected retroperitoneal angiosarcoma and multiple hepatic metastases. After chemotherapy with weekly paclitaxel and doxorubicin, angiosarcoma had progressed rapidly. Because few chemotherapeutic options were available for her, sunitinib (37.5 mg/day, daily) as a salvage regimen was administered. Although sunitinib was interrupted after two weeks due to hematologic abnormalities, some metastatic nodules were regressed. Therefore, sunitinib was recommenced at a reduced dose (25 mg/day, daily). Serial computed tomography scans showed variable response in each tumor, however, sunitinib at least delayed tumor progression, compared to previous chemotherapy. With this case report, we suggest sunitinib may be effective against angiosarcomas. When sunitinib is administered to patients with angiosarcomas, hematologic abnormalities should be monitored frequently as severe hematologic toxicity may be caused either by sunitinib per se or angiosarcoma. Copyright © 2009 Changhoon Yoo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction ongoing [4]. Herein, we report on a patient with advanced angiosarcoma who responded favorably to sunitinib after Angiosarcomas are rare subtypes of soft tissue sarcomas failure of paclitaxel and doxorubicin. originating from the vascular endothelium, and commonly occur in skin and soft tissues [1]. The clinical presentation 2. Case Report of angiosarcomas is heterogeneous and multidisciplinary treatment is often necessary [2]. To treat localized disease, A 52 year-old woman presented with an incidentally detected surgery followed by radiotherapy is a standard modality. In retroperitoneal mass and multiple liver nodules. Her ini- patients with advanced disease, paclitaxel- and doxorubicin- tial computed tomography (CT) and positron emission based regimens have been valuable [1, 2]. However, the tomography (PET) scans showed a huge retroperitoneal prognosis of patients with advanced angiosarcoma remains mass with direct invasion into the spleen, pancreas tail, poor, particularly when the condition progresses to a stage and stomach, and three metastatic hepatic nodules. The where cytotoxic agents are not effective [2, 3]. Today, with size of the retroperitoneal mass was 12.5 × 10 cm and the the development of drugs targeted to particular molecules dimensions of the hepatic metastases were 4.4 × 4.1cm involved in disease, several subtypes of sarcomas have been in segment IV, and 2.5 × 1.9cm and 1.2 × 1.1 cm in the successfully treated and a number of clinical trials are right posterior segment. Percutaneous needle biopsy of 2 Sarcoma (a) (b) (c) (d) Figure 1: Serial CT scans show variable response in retroperitoneal mass (arrowhead), multiple nodules of left hepatic lobe and two nodules (arrows) of right posterior lobe. (a) At initial presentation, (b) after one cycle of weekly paclitaxel, (c) after two cycles of doxorubicin, (d) after 3 months of sunitinib a hepatic nodule was performed. In histology, irregular and hematologic abnormalities were suggestive of the Kasabach- sinusoidal vascular proliferation, atypical endothelial lining, Merritt phenomenon (KMP), except that coagulopathy was and undifferentiated tumor cells were noted. These findings absent. One month later, the thrombocytopenia and anemia were consistent with angiosarcoma. This is supported by had regressed. At that time, a CT scan yielded interesting immunohistochemical study that shown tumor cells were findings. Some of the numerous scattered hepatic nodules positive for CD 31 and CD34. had disappeared, whereas others showed no change in Weekly paclitaxel (80 mg/m , on days 1, 8, 15, and 22, size, and the size of the retroperitoneal mass had also every 6 weeks) was administered as first-line chemotherapy. decreased, with evidence of internal necrosis, although two Our patient tolerated this regime well; no significant toxic- hepatic masses in the right posterior segment had progressed ities were observed. After one cycle of paclitaxel, a CT scan slightly. When we considered the prolonged interruption (Figure 1(b)) revealed an increase in size of the three hepatic to treatment caused by toxicity, and the rapid rate of nodules and multiple new hepatic metastases. Therefore, progression prior to the introduction of sunitinib, we formed we administered two cycles of second-line chemotherapy the view that sunitinib was active against our patient’s employing doxorubicin (60 mg/m , day 1, every 3 weeks). tumors. Therefore, we recommenced sunitinib treatment, In a follow-up CT scan (Figure 1(c)), the diameter of but at a reduced dose (25 mg/day, daily). Although grade 2 retroperitoneal mass was somewhat increased from 12.8 cm thrombocytopenia and MAHA reoccurred, these toxicities to 13.9 cm. However, twelve hepatic metastatic nodules were less severe than before. On monthly CT scans, some were newly developed and the size of previously detected hepatic metastases and the retroperitoneal mass responded hepatic nodules was increased within two months. The to sunitinib. However, two hepatic metastases of the right disease status was rapidly deteriorated and we had few posterior segment further progressed; it was thus difficult chemotherapeutic options, but our patient’s general perfor- to interpret any overall chemotherapeutic effect of sunitinib. mance was sufficiently good to allow us to consider further To evaluate any antitumor activity on the two hepatic chemotherapy. masses, grosstumor volume wasmeasuredonserialCT After a full and careful discussion with the patient, scans (Figure 1) and the volume doubling times (VDT) we administered sunitinib (37.5 mg/day, daily) as a salvage between each chemotherapy regime were calculated, using regimen. After 2 weeks of sunitinib, the patient presented the equation: VDT = [t × log 2]/log [V /V ], where t is t o to the clinic with severe asthenia, and chemotherapy was the interval in days between two scans, and V and V are o t interrupted. A laboratory investigation revealed grade 4 tumor volumes at the previous and current examination, thrombocytopenia, grade 3 anemia, fragmented RBCs in respectively. The hepatic mass tumors had VDT values the peripheral blood smear, and decreased levels of both of 16 days on paclitaxel, 66 days on doxorubicin, and serum haptoglobin and fibrinogen. Prothombin time was 145 days on sunitinib. We thus concluded that sunitinib within normal limits. These data supported a diagno- could delay tumor progression and the treatment was sis of microangiopathic hemolytic anemia (MAHA). The continued. Sarcoma 3 After an additional 3 months of sunitinib therapy, recur- responses in some hepatic nodules and the retroperitoneal rent hematologic toxicities associated with MAHA/KMP and mass, and decreased VDTs of two hepatic metastases in the concomitant deterioration of the patient’s general condition right posterior segment. Eventually, her disease did progress. caused chemotherapy to be interrupted. Two months later, We suggest that individual tumor nodules may respond the patient died of tumor invasion to her heart and inferior differently to sunitinib. Tumor nodules may gain or lose vena cava, about 11 months after initial diagnosis. sunitinib sensitivity by operation of an unknown molecular mechanism whereas other nodules may show constitutive sunitinib sensitivity, as found in the polyclonal evolution of 3. Discussion GIST treated with imatinib [15]. Angiosarcomas are derived from vascular endothelial cells In conclusion, this is the first case report indicating andaccount forlessthan2%ofsofttissuesarcomas that sunitinib may be effective against angiosarcomas. When [3]. The median survival time of patients with advanced sunitinib is administered to patients with angiosarcomas, angiosarcomas is about 7-8 months [2, 5]. Larger tumor hematologic abnormalities should be monitored frequently size (>5 cm), location in the retroperitoneum, and advanced as severe hematologic toxicity may be caused either by disease, are associated with poor prognosis [6]. Doxorubicin- sunitinib per se or angiosarcoma. Further studies are needed based chemotherapy has been considered the standard to explore sunitinib efficacy in angiosarcoma treatment. treatment for patients with advanced angiosarcomas as well References as for those with other soft tissue sarcomas [2, 6, 7]. Recent reports have shown that paclitaxel is also effective against [1] K.M.Skubitz andD.R.D’Adamo,“Sarcoma,” Mayo Clinic angiosarcoma [5, 7–10]. However, few clinical drug trials on Proceedings, vol. 82, no. 11, pp. 1409–1432, 2007. angiosarcoma patients have been carried out because of the [2] J.A.Abraham,F.J.Hornicek,A.M.Kaufman, et al., low incidence of the disease; hence very little information on “Treatment and outcome of 82 patients with angiosarcoma,” treatment is available, especially when the disease progresses Annals of Surgical Oncology, vol. 14, no. 6, pp. 1953–1967, after a short period of response to or stabilization with 2007. [3] M. G. Fury, C. R. Antonescu, K. J. Van Zee, M. F. Brennan, and doxorubicin or paclitaxel. R. G. Maki, “A 14-year retrospective review of angiosarcoma: Recently, tyrosine kinase inhibitors (TKIs) have emerged clinical characteristics, prognostic factors, and treatment as novel agents in the treatment of soft tissue sarcomas outcomes with surgery and chemotherapy,” Cancer Journal, [4]. There are no published clinical data on the use vol. 11, no. 3, pp. 241–247, 2005. of TKIs as therapy for angiosarcoma patients. However, [4] A. C. Shor, S. V. Agresta, G. Z. D’Amato, and V. K. Sondak, angiosarcomas originate from vascular endothelial tissues “Therapeutic potential of directed tyrosine kinase inhibitor and express proangiogenic factors including VEGF [4]. These therapy in sarcomas,” Cancer Control, vol. 15, no. 1, pp. 47– findings suggest a possible role for TKIs in angiosarcoma 54, 2008. treatment, and several TKIs directed against angiosarcomas [5] N. Penel, B. N. Bui, J.-O. Bay, et al., “Phase II trial of weekly are currently in clinical trials [4, 11]. Sunitinib, recently paclitaxel for unresectable angiosarcoma: the ANGIOTAX approved for patients with imatinib-refractory GIST and study,” Journal of Clinical Oncology, vol. 26, no. 32, pp. 5269– 5274, 2008. advanced renal cell carcinoma, inhibits several tyrosine [6] M. Koch, G. P. Nielsen, and S. S. Yoon, “Malignant tumors of kinases and has antiangiogenic activity. The drug may thus blood vessels: angiosarcomas, hemangioendotheliomas, and be active against vascular endothelial cell-derived or vascular hemangioperictyomas,” Journal of Surgical Oncology, vol. 97, endothelial cell-dependent cancers [4, 11]. no. 4, pp. 321–329, 2008. During treatment with sunitinib, our patient suffered [7] N. Penel, A. Lansiaux, and A. Adenis, “Angiosarcomas and from severe thrombocytopenia and MAHA. Although suni- taxanes,” Current Treatment Options in Oncology, vol. 8, no. tinib suppresses bone marrow function, and a single case 6, pp. 428–434, 2007. report of sunitinib-induced thrombotic thrombocytopenia [8] K. M. Skubitz and P. A. Haddad, “Paclitaxel and pegylated- purpura has appeared [12], it is difficult to conclude that the liposomal doxorubicin are both active in angiosarcoma,” reported hematologic abnormalities were caused by sunitinib Cancer, vol. 104, no. 2, pp. 361–366, 2005. alone, becausesuchproblemshavebeenreportedinonly [9] M. Schlemmer, P. Reichardt, J. Verweij, et al., “Paclitaxel very few GIST or renal cell carcinoma patients enrolled in in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma large phase III clinical studies. The occurrence of severe group,” European Journal of Cancer, vol. 44, no. 16, pp. 2433– anemia, and thrombocytopenia with laboratory features of 2436, 2008. MAHA, might be in part attributable to KMP, a syndrome [10] F. Fata, E. O’Reilly, D. Ilson, et al., “Paclitaxel in the treatment associated with vascular tumors, which shows features of patients with anglosarcoma of the scalp or face,” Cancer, vol. similar to those of MAHA and consumptive coagulopathy 86, no. 10, pp. 2034–2037, 1999. [12–14]. [11] L. Balasubramanian and A. M. Evens, “Targeting angiogenesis In this case report, our patient had advanced angiosar- for the treatment of sarcoma,” Current Opinion in Oncology, coma and her clinical features suggested the worst possible vol. 18, no. 4, pp. 354–359, 2006. outcome [6]. The tumor was progressing rapidly and [12] E. Kapiteijn, A. Brand, J. Kroep, and H. Gelderblom, “Suni- showed no response to conventional chemotherapy. We tinib induced hypertension, thrombotic microangiopathy and used sunitinib as a last resort. The overall response to reversible posterior leukencephalopathy syndrome,” Annals of sunitinib was hard to evaluate, but we observed dramatic Oncology, vol. 18, no. 10, pp. 1745–1747, 2007. 4 Sarcoma [13] D. M. Adams and M. S. Wentzel, “The role of the hematolo- gist/oncologist in the care of patients with vascular anomalies,” Pediatric Clinics of North America, vol. 55, no. 2, pp. 339–355, [14] C. Alliot,B.Tribout,M.Barrios,and M.-F.Gontier,“Angiosar- coma variant of Kasabach-Merritt syndrome,” European Jour- nal of Gastroenterology and Hepatology, vol. 13, no. 6, pp. 731– 734, 2001. [15] E. Wardelmann, S. Merkelbach-Bruse, K. Pauls, et al., “Poly- clonal evolution of multiple secondary KIT mutations in gas- trointestinal stromal tumors under treatment with imatinib mesylate,” Clinical Cancer Research, vol. 12, no. 6, pp. 1743– 1749, 2006. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Sarcoma Hindawi Publishing Corporation

Angiosarcoma of the Retroperitoneum: Report on a Patient Treated with Sunitinib

Download PDF
5 pages

Loading next page...
 
/lp/hindawi-publishing-corporation/angiosarcoma-of-the-retroperitoneum-report-on-a-patient-treated-with-PHlmwRnDxk

References (18)

Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2009 Changhoon Yoo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
1357-714X
eISSN
1369-1643
DOI
10.1155/2009/360875
Publisher site
See Article on Publisher Site

Abstract

Hindawi Publishing Corporation Sarcoma Volume 2009, Article ID 360875, 4 pages doi:10.1155/2009/360875 Case Report Angiosarcomaofthe Retroperitoneum: Report on a Patient Treated with Sunitinib 1 1 1 2 3 Changhoon Yoo, Jeong-Eun Kim, Shin-Kyo Yoon, Song Cheol Kim, Jin-Hee Ahn, 3 3 3 Tae Won Kim, Cheolwon Suh, and Jae-Lyun Lee Department of Internal medicine, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736, South Korea Department of Surgery, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736, South Korea Department of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736, South Korea Correspondence should be addressed to Jae-Lyun Lee, jaelyun@amc.seoul.kr Received 13 January 2009; Accepted 20 April 2009 Recommended by Cyril Fisher A 52 year-old woman presented with an incidentally detected retroperitoneal angiosarcoma and multiple hepatic metastases. After chemotherapy with weekly paclitaxel and doxorubicin, angiosarcoma had progressed rapidly. Because few chemotherapeutic options were available for her, sunitinib (37.5 mg/day, daily) as a salvage regimen was administered. Although sunitinib was interrupted after two weeks due to hematologic abnormalities, some metastatic nodules were regressed. Therefore, sunitinib was recommenced at a reduced dose (25 mg/day, daily). Serial computed tomography scans showed variable response in each tumor, however, sunitinib at least delayed tumor progression, compared to previous chemotherapy. With this case report, we suggest sunitinib may be effective against angiosarcomas. When sunitinib is administered to patients with angiosarcomas, hematologic abnormalities should be monitored frequently as severe hematologic toxicity may be caused either by sunitinib per se or angiosarcoma. Copyright © 2009 Changhoon Yoo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction ongoing [4]. Herein, we report on a patient with advanced angiosarcoma who responded favorably to sunitinib after Angiosarcomas are rare subtypes of soft tissue sarcomas failure of paclitaxel and doxorubicin. originating from the vascular endothelium, and commonly occur in skin and soft tissues [1]. The clinical presentation 2. Case Report of angiosarcomas is heterogeneous and multidisciplinary treatment is often necessary [2]. To treat localized disease, A 52 year-old woman presented with an incidentally detected surgery followed by radiotherapy is a standard modality. In retroperitoneal mass and multiple liver nodules. Her ini- patients with advanced disease, paclitaxel- and doxorubicin- tial computed tomography (CT) and positron emission based regimens have been valuable [1, 2]. However, the tomography (PET) scans showed a huge retroperitoneal prognosis of patients with advanced angiosarcoma remains mass with direct invasion into the spleen, pancreas tail, poor, particularly when the condition progresses to a stage and stomach, and three metastatic hepatic nodules. The where cytotoxic agents are not effective [2, 3]. Today, with size of the retroperitoneal mass was 12.5 × 10 cm and the the development of drugs targeted to particular molecules dimensions of the hepatic metastases were 4.4 × 4.1cm involved in disease, several subtypes of sarcomas have been in segment IV, and 2.5 × 1.9cm and 1.2 × 1.1 cm in the successfully treated and a number of clinical trials are right posterior segment. Percutaneous needle biopsy of 2 Sarcoma (a) (b) (c) (d) Figure 1: Serial CT scans show variable response in retroperitoneal mass (arrowhead), multiple nodules of left hepatic lobe and two nodules (arrows) of right posterior lobe. (a) At initial presentation, (b) after one cycle of weekly paclitaxel, (c) after two cycles of doxorubicin, (d) after 3 months of sunitinib a hepatic nodule was performed. In histology, irregular and hematologic abnormalities were suggestive of the Kasabach- sinusoidal vascular proliferation, atypical endothelial lining, Merritt phenomenon (KMP), except that coagulopathy was and undifferentiated tumor cells were noted. These findings absent. One month later, the thrombocytopenia and anemia were consistent with angiosarcoma. This is supported by had regressed. At that time, a CT scan yielded interesting immunohistochemical study that shown tumor cells were findings. Some of the numerous scattered hepatic nodules positive for CD 31 and CD34. had disappeared, whereas others showed no change in Weekly paclitaxel (80 mg/m , on days 1, 8, 15, and 22, size, and the size of the retroperitoneal mass had also every 6 weeks) was administered as first-line chemotherapy. decreased, with evidence of internal necrosis, although two Our patient tolerated this regime well; no significant toxic- hepatic masses in the right posterior segment had progressed ities were observed. After one cycle of paclitaxel, a CT scan slightly. When we considered the prolonged interruption (Figure 1(b)) revealed an increase in size of the three hepatic to treatment caused by toxicity, and the rapid rate of nodules and multiple new hepatic metastases. Therefore, progression prior to the introduction of sunitinib, we formed we administered two cycles of second-line chemotherapy the view that sunitinib was active against our patient’s employing doxorubicin (60 mg/m , day 1, every 3 weeks). tumors. Therefore, we recommenced sunitinib treatment, In a follow-up CT scan (Figure 1(c)), the diameter of but at a reduced dose (25 mg/day, daily). Although grade 2 retroperitoneal mass was somewhat increased from 12.8 cm thrombocytopenia and MAHA reoccurred, these toxicities to 13.9 cm. However, twelve hepatic metastatic nodules were less severe than before. On monthly CT scans, some were newly developed and the size of previously detected hepatic metastases and the retroperitoneal mass responded hepatic nodules was increased within two months. The to sunitinib. However, two hepatic metastases of the right disease status was rapidly deteriorated and we had few posterior segment further progressed; it was thus difficult chemotherapeutic options, but our patient’s general perfor- to interpret any overall chemotherapeutic effect of sunitinib. mance was sufficiently good to allow us to consider further To evaluate any antitumor activity on the two hepatic chemotherapy. masses, grosstumor volume wasmeasuredonserialCT After a full and careful discussion with the patient, scans (Figure 1) and the volume doubling times (VDT) we administered sunitinib (37.5 mg/day, daily) as a salvage between each chemotherapy regime were calculated, using regimen. After 2 weeks of sunitinib, the patient presented the equation: VDT = [t × log 2]/log [V /V ], where t is t o to the clinic with severe asthenia, and chemotherapy was the interval in days between two scans, and V and V are o t interrupted. A laboratory investigation revealed grade 4 tumor volumes at the previous and current examination, thrombocytopenia, grade 3 anemia, fragmented RBCs in respectively. The hepatic mass tumors had VDT values the peripheral blood smear, and decreased levels of both of 16 days on paclitaxel, 66 days on doxorubicin, and serum haptoglobin and fibrinogen. Prothombin time was 145 days on sunitinib. We thus concluded that sunitinib within normal limits. These data supported a diagno- could delay tumor progression and the treatment was sis of microangiopathic hemolytic anemia (MAHA). The continued. Sarcoma 3 After an additional 3 months of sunitinib therapy, recur- responses in some hepatic nodules and the retroperitoneal rent hematologic toxicities associated with MAHA/KMP and mass, and decreased VDTs of two hepatic metastases in the concomitant deterioration of the patient’s general condition right posterior segment. Eventually, her disease did progress. caused chemotherapy to be interrupted. Two months later, We suggest that individual tumor nodules may respond the patient died of tumor invasion to her heart and inferior differently to sunitinib. Tumor nodules may gain or lose vena cava, about 11 months after initial diagnosis. sunitinib sensitivity by operation of an unknown molecular mechanism whereas other nodules may show constitutive sunitinib sensitivity, as found in the polyclonal evolution of 3. Discussion GIST treated with imatinib [15]. Angiosarcomas are derived from vascular endothelial cells In conclusion, this is the first case report indicating andaccount forlessthan2%ofsofttissuesarcomas that sunitinib may be effective against angiosarcomas. When [3]. The median survival time of patients with advanced sunitinib is administered to patients with angiosarcomas, angiosarcomas is about 7-8 months [2, 5]. Larger tumor hematologic abnormalities should be monitored frequently size (>5 cm), location in the retroperitoneum, and advanced as severe hematologic toxicity may be caused either by disease, are associated with poor prognosis [6]. Doxorubicin- sunitinib per se or angiosarcoma. Further studies are needed based chemotherapy has been considered the standard to explore sunitinib efficacy in angiosarcoma treatment. treatment for patients with advanced angiosarcomas as well References as for those with other soft tissue sarcomas [2, 6, 7]. Recent reports have shown that paclitaxel is also effective against [1] K.M.Skubitz andD.R.D’Adamo,“Sarcoma,” Mayo Clinic angiosarcoma [5, 7–10]. However, few clinical drug trials on Proceedings, vol. 82, no. 11, pp. 1409–1432, 2007. angiosarcoma patients have been carried out because of the [2] J.A.Abraham,F.J.Hornicek,A.M.Kaufman, et al., low incidence of the disease; hence very little information on “Treatment and outcome of 82 patients with angiosarcoma,” treatment is available, especially when the disease progresses Annals of Surgical Oncology, vol. 14, no. 6, pp. 1953–1967, after a short period of response to or stabilization with 2007. [3] M. G. Fury, C. R. Antonescu, K. J. Van Zee, M. F. Brennan, and doxorubicin or paclitaxel. R. G. Maki, “A 14-year retrospective review of angiosarcoma: Recently, tyrosine kinase inhibitors (TKIs) have emerged clinical characteristics, prognostic factors, and treatment as novel agents in the treatment of soft tissue sarcomas outcomes with surgery and chemotherapy,” Cancer Journal, [4]. There are no published clinical data on the use vol. 11, no. 3, pp. 241–247, 2005. of TKIs as therapy for angiosarcoma patients. However, [4] A. C. Shor, S. V. Agresta, G. Z. D’Amato, and V. K. Sondak, angiosarcomas originate from vascular endothelial tissues “Therapeutic potential of directed tyrosine kinase inhibitor and express proangiogenic factors including VEGF [4]. These therapy in sarcomas,” Cancer Control, vol. 15, no. 1, pp. 47– findings suggest a possible role for TKIs in angiosarcoma 54, 2008. treatment, and several TKIs directed against angiosarcomas [5] N. Penel, B. N. Bui, J.-O. Bay, et al., “Phase II trial of weekly are currently in clinical trials [4, 11]. Sunitinib, recently paclitaxel for unresectable angiosarcoma: the ANGIOTAX approved for patients with imatinib-refractory GIST and study,” Journal of Clinical Oncology, vol. 26, no. 32, pp. 5269– 5274, 2008. advanced renal cell carcinoma, inhibits several tyrosine [6] M. Koch, G. P. Nielsen, and S. S. Yoon, “Malignant tumors of kinases and has antiangiogenic activity. The drug may thus blood vessels: angiosarcomas, hemangioendotheliomas, and be active against vascular endothelial cell-derived or vascular hemangioperictyomas,” Journal of Surgical Oncology, vol. 97, endothelial cell-dependent cancers [4, 11]. no. 4, pp. 321–329, 2008. During treatment with sunitinib, our patient suffered [7] N. Penel, A. Lansiaux, and A. Adenis, “Angiosarcomas and from severe thrombocytopenia and MAHA. Although suni- taxanes,” Current Treatment Options in Oncology, vol. 8, no. tinib suppresses bone marrow function, and a single case 6, pp. 428–434, 2007. report of sunitinib-induced thrombotic thrombocytopenia [8] K. M. Skubitz and P. A. Haddad, “Paclitaxel and pegylated- purpura has appeared [12], it is difficult to conclude that the liposomal doxorubicin are both active in angiosarcoma,” reported hematologic abnormalities were caused by sunitinib Cancer, vol. 104, no. 2, pp. 361–366, 2005. alone, becausesuchproblemshavebeenreportedinonly [9] M. Schlemmer, P. Reichardt, J. Verweij, et al., “Paclitaxel very few GIST or renal cell carcinoma patients enrolled in in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma large phase III clinical studies. The occurrence of severe group,” European Journal of Cancer, vol. 44, no. 16, pp. 2433– anemia, and thrombocytopenia with laboratory features of 2436, 2008. MAHA, might be in part attributable to KMP, a syndrome [10] F. Fata, E. O’Reilly, D. Ilson, et al., “Paclitaxel in the treatment associated with vascular tumors, which shows features of patients with anglosarcoma of the scalp or face,” Cancer, vol. similar to those of MAHA and consumptive coagulopathy 86, no. 10, pp. 2034–2037, 1999. [12–14]. [11] L. Balasubramanian and A. M. Evens, “Targeting angiogenesis In this case report, our patient had advanced angiosar- for the treatment of sarcoma,” Current Opinion in Oncology, coma and her clinical features suggested the worst possible vol. 18, no. 4, pp. 354–359, 2006. outcome [6]. The tumor was progressing rapidly and [12] E. Kapiteijn, A. Brand, J. Kroep, and H. Gelderblom, “Suni- showed no response to conventional chemotherapy. We tinib induced hypertension, thrombotic microangiopathy and used sunitinib as a last resort. The overall response to reversible posterior leukencephalopathy syndrome,” Annals of sunitinib was hard to evaluate, but we observed dramatic Oncology, vol. 18, no. 10, pp. 1745–1747, 2007. 4 Sarcoma [13] D. M. Adams and M. S. Wentzel, “The role of the hematolo- gist/oncologist in the care of patients with vascular anomalies,” Pediatric Clinics of North America, vol. 55, no. 2, pp. 339–355, [14] C. Alliot,B.Tribout,M.Barrios,and M.-F.Gontier,“Angiosar- coma variant of Kasabach-Merritt syndrome,” European Jour- nal of Gastroenterology and Hepatology, vol. 13, no. 6, pp. 731– 734, 2001. [15] E. Wardelmann, S. Merkelbach-Bruse, K. Pauls, et al., “Poly- clonal evolution of multiple secondary KIT mutations in gas- trointestinal stromal tumors under treatment with imatinib mesylate,” Clinical Cancer Research, vol. 12, no. 6, pp. 1743– 1749, 2006. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

Journal

Sarcoma – Hindawi Publishing Corporation

Published: May 20, 2009

There are no references for this article.