Angiosarcoma of the scalp successfully treated with pazopanib
Authors: Hajime Tomita, Yuta Koike, Misachi Asai, Fumihide Ogawa, Kuniko Abe, Miki Tanioka, Atsushi Utani
Journal: Journal of the American Academy of Dermatology (2013)

To the Editor: Angiosarcoma of the scalp has one of the worst prognoses among malignant skin tumors.1Young R.J. Brown N.J. Reed M.W. Hughes D. Woll P.J. Angiosarcoma.Lancet Oncol. 2010; 11: 983-991Abstract Full Text Full Text PDF PubMed Scopus (529) Google Scholar Standard treatment guidelines for angiosarcoma do not currently exist.1Young R.J. Brown N.J. Reed M.W. Hughes D. Woll P.J. Angiosarcoma.Lancet Oncol. 2010; 11: 983-991Abstract Full Text Full Text PDF PubMed Scopus (529) Google Scholar To the best of our knowledge, this is the first case of angiosarcoma of the scalp that responded significantly to oral pazopanib administration.A 63-year-old man presented with scalp tumors that had developed 2 months earlier. Histopathologic examination revealed atypical hyperchromatic endothelial cells, which were positive for CD31, CD34, D2-40, and VEGFR2 and which formed vascular channels. The two tumors, 60 and 20 mm in diameter, were excised with negative surgical margins; however, 4 additional surgical operations were required to remove multiple recurrences. Subsequently, weekly docetaxel (25 mg/m2, on days 1, 8, and 15, and every 4 weeks thereafter) was administered at 8 months after initial onset; however, this treatment regimen failed to suppress the development of further cutaneous tumors. Therefore, intravenous recombinant interleukin-2 (7 × 105 U/day) combined with a 100-Gy electron beam irradiation was administered for 11 to 18 months after onset. However, new tumors grew outside the area of irradiation. At 18 months after onset, the patient developed multiple ulcers on the scalp, a 30- × 20-mm indurated plaque on the left cheek, marked edema of the face (Fig 1, A), and enlargement of the involvement of multiple cervical, mandibular, and intraparotid lymph nodes (Fig 2, A).Fig 2Angiosarcoma treated with pazopanib. Serial computed tomography scans. Scans show varying responses in multiple intraparotid lymph nodes (arrows). A, Before pazopanib therapy. B, Nineteen days after the commencement of pazopanib therapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Owing to the refractory nature of the tumors, pazopanib treatment was initiated at a dose of 800 mg once daily. At day 3 of pazopanib treatment, edema of the face began to subside, and the patient began to open both eyes; the edema finally disappeared by day 14. The left cheek indurated plaque completely disappeared (Fig 1, B). In addition, a computed tomography scan at day 19 showed shrinking of the multiple cervical, mandibular, and intraparotid lymph nodes (Fig 2, B). Toxic side effects of grade 3 thrombocytopenia and grade 2 neutropenia were apparent. Pazopanib therapy of 800 mg was discontinued after 2 weeks and restarted at a reduced dose of 600 mg once daily. Thereafter, the appearance of grade 3 proteinuria required that the dose be reduced further to 400 mg once daily. However, partial tumor reduction has been maintained for 26 weeks and the patient is now undergoing a pazopanib treatment without toxic side effects.Pazopanib is a multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α/β, and c-kit.2Heudel P. Cassier P. Derbel O. Dufresne A. Meeus P. Thiesse P. et al.Pazopanib for the treatment of soft-tissue sarcoma.Clin Pharmacol. 2012; 4: 65-70PubMed Google Scholar VEGFR-2 is up-regulated in angiosarcoma.3Miettinen M. Rikala M.S. Rys J. Lasota J. Wang Z.F. Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors.Am J Surg Pathol. 2012; 36: 629-639Crossref PubMed Scopus (60) Google Scholar Angiosarcoma cells in the present case were also positive for VEGFR-2, suggesting that signals impinging on VEGFR-2 stimulate tumorigenesis. Accordingly, it is possible that pazopanib led to clinical improvement by inhibiting VEGFR-2 tyrosine kinase activity.The administration of pazopanib results in rare toxic effects.4Sternberg C.N. Hawkins R.E. Wagstaff J. Salman P. Mardiak J. Barrios C.H. et al.A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update.Eur J Cancer. 2013; 49: 1287-1296Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar It is possible that taxane chemotherapy contributed to these toxic effects.Other VEGFR inhibitors (bevacizumab, sorafenib, and sunitinib) have also been reported to be effective treatments for angiosarcoma.1Young R.J. Brown N.J. Reed M.W. Hughes D. Woll P.J. Angiosarcoma.Lancet Oncol. 2010; 11: 983-991Abstract Full Text Full Text PDF PubMed Scopus (529) Google Scholar Thus, VEGFR inhibitors, such as pazopanib, may provide an additional option for the treatment of angiosarcoma. To the Editor: Angiosarcoma of the scalp has one of the worst prognoses among malignant skin tumors.1Young R.J. Brown N.J. Reed M.W. Hughes D. Woll P.J. Angiosarcoma.Lancet Oncol. 2010; 11: 983-991Abstract Full Text Full Text PDF PubMed Scopus (529) Google Scholar Standard treatment guidelines for angiosarcoma do not currently exist.1Young R.J. Brown N.J. Reed M.W. Hughes D. Woll P.J. Angiosarcoma.Lancet Oncol. 2010; 11: 983-991Abstract Full Text Full Text PDF PubMed Scopus (529) Google Scholar To the best of our knowledge, this is the first case of angiosarcoma of the scalp that responded significantly to oral pazopanib administration. A 63-year-old man presented with scalp tumors that had developed 2 months earlier. Histopathologic examination revealed atypical hyperchromatic endothelial cells, which were positive for CD31, CD34, D2-40, and VEGFR2 and which formed vascular channels. The two tumors, 60 and 20 mm in diameter, were excised with negative surgical margins; however, 4 additional surgical operations were required to remove multiple recurrences. Subsequently, weekly docetaxel (25 mg/m2, on days 1, 8, and 15, and every 4 weeks thereafter) was administered at 8 months after initial onset; however, this treatment regimen failed to suppress the development of further cutaneous tumors. Therefore, intravenous recombinant interleukin-2 (7 × 105 U/day) combined with a 100-Gy electron beam irradiation was administered for 11 to 18 months after onset. However, new tumors grew outside the area of irradiation. At 18 months after onset, the patient developed multiple ulcers on the scalp, a 30- × 20-mm indurated plaque on the left cheek, marked edema of the face (Fig 1, A), and enlargement of the involvement of multiple cervical, mandibular, and intraparotid lymph nodes (Fig 2, A). Owing to the refractory nature of the tumors, pazopanib treatment was initiated at a dose of 800 mg once daily. At day 3 of pazopanib treatment, edema of the face began to subside, and the patient began to open both eyes; the edema finally disappeared by day 14. The left cheek indurated plaque completely disappeared (Fig 1, B). In addition, a computed tomography scan at day 19 showed shrinking of the multiple cervical, mandibular, and intraparotid lymph nodes (Fig 2, B). Toxic side effects of grade 3 thrombocytopenia and grade 2 neutropenia were apparent. Pazopanib therapy of 800 mg was discontinued after 2 weeks and restarted at a reduced dose of 600 mg once daily. Thereafter, the appearance of grade 3 proteinuria required that the dose be reduced further to 400 mg once daily. However, partial tumor reduction has been maintained for 26 weeks and the patient is now undergoing a pazopanib treatment without toxic side effects. Pazopanib is a multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α/β, and c-kit.2Heudel P. Cassier P. Derbel O. Dufresne A. Meeus P. Thiesse P. et al.Pazopanib for the treatment of soft-tissue sarcoma.Clin Pharmacol. 2012; 4: 65-70PubMed Google Scholar VEGFR-2 is up-regulated in angiosarcoma.3Miettinen M. Rikala M.S. Rys J. Lasota J. Wang Z.F. Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors.Am J Surg Pathol. 2012; 36: 629-639Crossref PubMed Scopus (60) Google Scholar Angiosarcoma cells in the present case were also positive for VEGFR-2, suggesting that signals impinging on VEGFR-2 stimulate tumorigenesis. Accordingly, it is possible that pazopanib led to clinical improvement by inhibiting VEGFR-2 tyrosine kinase activity. The administration of pazopanib results in rare toxic effects.4Sternberg C.N. Hawkins R.E. Wagstaff J. Salman P. Mardiak J. Barrios C.H. et al.A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update.Eur J Cancer. 2013; 49: 1287-1296Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar It is possible that taxane chemotherapy contributed to these toxic effects. Other VEGFR inhibitors (bevacizumab, sorafenib, and sunitinib) have also been reported to be effective treatments for angiosarcoma.1Young R.J. Brown N.J. Reed M.W. Hughes D. Woll P.J. Angiosarcoma.Lancet Oncol. 2010; 11: 983-991Abstract Full Text Full Text PDF PubMed Scopus (529) Google Scholar Thus, VEGFR inhibitors, such as pazopanib, may provide an additional option for the treatment of angiosarcoma.