A Kaposi's sarcoma complete clinical response after sorafenib administration
Authors: A. Ardavanis, D. Doufexis, P. Kountourakis, G. Rigatos
Journal: Annals of Oncology (2008)

We present an unexpected complete clinical response of Kaposi sarcoma (KS) to Sorafenib (Nexavar®) administered as treatment to a renal cell carcinoma in a 60-year-old man.The patient presented with hematuria to our department in September 2006. A tumor in his left kidney was diagnosed and subsequently was radically operated; biopsy showed a Fuhrman grades 3–4 and a stage II (AJCC 2002) renal cell carcinoma. In July 2007, due to central nervous system (CNS) symptoms, brain computed tomography revealed two metastatic lesions; whole cranial irradiation—consisted of a 10 × 3 Gy dose—was administered and stereotactic radiosurgery (20 Gy) (Cyberknife) was followed.In October 2007, several raised pigmented skin lesions came up. Biopsy revealed a KS. No human immunodeficiency virus or herpes infection was documented and therefore it was characterized as sporadic type; full disease extent work-up at that time showed persistence of CNS lesions and no other metastatic sites.A modern targeted therapy was then considered with the hope of regression of the CNS deposits and delaying growth of eventual renal cell cancer (RCC) micrometastases. However, given the presence of coronary artery disease (treated with simvastatin, aspirin and metoprolol, with a left ventricular ejection fraction of 58% by equilibrium radionuclide ventriculography), sunitinib with its known side-effects on the cardiovascular system did not appear to be a safe option; we therefore decided to give sorafenib instead because it was not until after this decision that the respective side-effects of sorafenib came to our knowledge.After 2 months of Nexavar®, 400 mg b.i.d., well tolerated (only moderate skin rash), all Kaposi lesions regressed spectacularly (absolute flattening, only pigmentation persisting) while brain metastases were stable. So far, 2 months after documentation of remission, the latter persists and treatment is being continued without significant toxicity and a good performance status.KS is a highly vascular tumor and is believed to be caused by Human herpesvirus 8 (HHV8, KS-associated herpesvirus) [1.Boshoff C. Weiss R. AIDS-related malignancies.Nat Rev Cancer. 2002; 2: 373-382Crossref PubMed Scopus (308) Google Scholar]. HHV8 and KS cells produce cytokines that stimulate and promote angiogenesis through the production of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, transforming growth factor beta, platelet-derived growth factor alpha (PDGF-α), interleukin 1, and interleukin 6 [2.Cornali E. Zietz C. Benelli R. et al.Vascular endothelial growth factor regulates angiogenesis and vascular permeability in Kaposi's sarcoma.Am J Pathol. 1996; 149: 1851-1869PubMed Google Scholar, 3.Samaniego F. Markham P.D. Gendelman R. et al.Vascular endothelial growth factor and basic fibroblast growth factor present in Kaposi's sarcoma (KS) are induced by inflammatory cytokines and synergize to promote vascular permeability and KS lesion development.Am J Pathol. 1998; 152: 1433-1443PubMed Google Scholar]. Sorafenib is a multikinase inhibitor that inhibits VEGF receptors, PDGF receptors, fms-like tyrosine kinase 3, stem cell factor receptor.v-raf-leukemia viral oncogene 1 and v-raf murine sarcoma viral oncogene homolog B1 has been shown to prevent the growth of tumors [4.Flaherty K.T. Sorafenib in renal cell carcinoma.Clin Cancer Res. 2007; 13: 747s-752sCrossref PubMed Scopus (53) Google Scholar]; these effects might underlie the response of KS lesions observed.Sorafenib revealed activity in preventing brain metastasis progression from RCC in a patient with cardiovascular risk and an unexpected complete remission in a concomitant KS. Therefore, our findings merit further investigation. We present an unexpected complete clinical response of Kaposi sarcoma (KS) to Sorafenib (Nexavar®) administered as treatment to a renal cell carcinoma in a 60-year-old man. The patient presented with hematuria to our department in September 2006. A tumor in his left kidney was diagnosed and subsequently was radically operated; biopsy showed a Fuhrman grades 3–4 and a stage II (AJCC 2002) renal cell carcinoma. In July 2007, due to central nervous system (CNS) symptoms, brain computed tomography revealed two metastatic lesions; whole cranial irradiation—consisted of a 10 × 3 Gy dose—was administered and stereotactic radiosurgery (20 Gy) (Cyberknife) was followed. In October 2007, several raised pigmented skin lesions came up. Biopsy revealed a KS. No human immunodeficiency virus or herpes infection was documented and therefore it was characterized as sporadic type; full disease extent work-up at that time showed persistence of CNS lesions and no other metastatic sites. A modern targeted therapy was then considered with the hope of regression of the CNS deposits and delaying growth of eventual renal cell cancer (RCC) micrometastases. However, given the presence of coronary artery disease (treated with simvastatin, aspirin and metoprolol, with a left ventricular ejection fraction of 58% by equilibrium radionuclide ventriculography), sunitinib with its known side-effects on the cardiovascular system did not appear to be a safe option; we therefore decided to give sorafenib instead because it was not until after this decision that the respective side-effects of sorafenib came to our knowledge. After 2 months of Nexavar®, 400 mg b.i.d., well tolerated (only moderate skin rash), all Kaposi lesions regressed spectacularly (absolute flattening, only pigmentation persisting) while brain metastases were stable. So far, 2 months after documentation of remission, the latter persists and treatment is being continued without significant toxicity and a good performance status. KS is a highly vascular tumor and is believed to be caused by Human herpesvirus 8 (HHV8, KS-associated herpesvirus) [1.Boshoff C. Weiss R. AIDS-related malignancies.Nat Rev Cancer. 2002; 2: 373-382Crossref PubMed Scopus (308) Google Scholar]. HHV8 and KS cells produce cytokines that stimulate and promote angiogenesis through the production of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, transforming growth factor beta, platelet-derived growth factor alpha (PDGF-α), interleukin 1, and interleukin 6 [2.Cornali E. Zietz C. Benelli R. et al.Vascular endothelial growth factor regulates angiogenesis and vascular permeability in Kaposi's sarcoma.Am J Pathol. 1996; 149: 1851-1869PubMed Google Scholar, 3.Samaniego F. Markham P.D. Gendelman R. et al.Vascular endothelial growth factor and basic fibroblast growth factor present in Kaposi's sarcoma (KS) are induced by inflammatory cytokines and synergize to promote vascular permeability and KS lesion development.Am J Pathol. 1998; 152: 1433-1443PubMed Google Scholar]. Sorafenib is a multikinase inhibitor that inhibits VEGF receptors, PDGF receptors, fms-like tyrosine kinase 3, stem cell factor receptor. v-raf-leukemia viral oncogene 1 and v-raf murine sarcoma viral oncogene homolog B1 has been shown to prevent the growth of tumors [4.Flaherty K.T. Sorafenib in renal cell carcinoma.Clin Cancer Res. 2007; 13: 747s-752sCrossref PubMed Scopus (53) Google Scholar]; these effects might underlie the response of KS lesions observed. Sorafenib revealed activity in preventing brain metastasis progression from RCC in a patient with cardiovascular risk and an unexpected complete remission in a concomitant KS. Therefore, our findings merit further investigation.