There have been great advances in the understanding of the pathogenesis
There have been great advances in the understanding of the pathogenesis of Kaposi’s sarcoma (KS). The better understanding of autocrine and paracrine factors in the proliferation and differentiation of KS cells [3]has provided a potential benefit derived from targeted therapy, a therapeutic field which has achieved an enormous development over the last decade. There are few reports regarding novel treatment options for KS, this includes the use of Imatinib in AIDS KS [4] and the use of Sirolimus in renal transplant KS patients [5].Page 1 of(page number not for citation purposes)BMC Nephrology 2007, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29072704 8:http://www.biomedcentral.com/1471-2369/8/Imatinib is a tyrosine-kinase inhibitor that induces apoptosis in Bcr-Abl positive cell lines, platelet-derived growth factor positive cells and c-kit positive gastrointestinal stromal cells. Limited information exists regarding its effects on KS cells [4]. Though the drug safety profile is good it can induce severe adverse events [6]. Because Imatinib is metabolized through the CYP3A3 enzyme it can result in adverse drugs interaction. Its safety in patients with renalinsufficiency or kidney graft is unknown. HHV-8 up-regulates the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR in endothelial cells. In vitro infection of human primary endothelial cells with HHV-8 causes long-term proliferation and survival of cells. Blocking the interaction between VEGF and Flk-1/ KDR can abolish VEGF induced proliferation. Sirolimus an immunosuppressive drug used in kidney transplantation [5], exhibits antiangiogenic activity related to impaired production of VEGF and limited proliferative response of endothelial cells to stimulation by VEGF, therefore inhibiting KS progression. Here we report a case of a kidney transplant patient who after unsuccessful treatments with different chemotherapeutics was given Imatinib for refractory and extensive cutaneous KS that resulted in severe toxicity and no clinical benefit. In contrast shifting the patient’s immunosuppressive maintenance therapy to Sirolimus led within one year to over 80 regression of the KS and is still showing sign of regression (Table 1)diagnosed as KS by skin biopsy. He received 19 administrations of vincristine (1 mg) and bleomycin (15 mg) weekly that resulted in flattening and fading of the lesions. Treatment was discontinued for two Olumacostat glasaretilMedChemExpress Olumacostat glasaretil months, and KS recurred, with pain and edema in both legs. On July 2002, with an almost 100 involvement of his lower limbs skin with KS but no visceral involvement he received 50 mg of liposomal-adriamycin. In addition, he was then prescribed valganciclovir 450 mg BID (corrected for creatinine clearance) [7] and three additional administrations of liposomal-adriamycin, up to December 2002. He showed 40 response again with early relapse. On January 2003 the patient developed disseminated herpes zoster, which was treated with IV acyclovir. In May 2003 KS progression was observed and received radiotherapy with no benefit Figure 1. In August 2003 he started oral etoposide at 50 mg QD for two weeks followed by two weeks off until May 2004 achieving a very slow 50 response. Tolerance was good and serum creatinine remain stable at around 1,4 mg/dl. Mophetil mycophenolate dose was reduced to 1 g/day and prednisone to 2.5 mg/day. On May 2004 the patient requested a second opinion and was prescribed Imatinib 200 mg qd for two weeks followed by 400 mg qd. After four weeks of Imatinib, his health deteriorated rapidly,.
