Treatments of AIDS-related Kaposi's sarcoma

Aversa, Savina; Cattelan, Anna María; Salvagno, Luigi; Crivellari, Gino; Banna, Giuseppe Luigi; Trevenzoli, Marco; Chiarion-Sileni, Vanna; Monfardini, S.

doi:10.1016/j.critrevonc.2004.10.009

Cited by 49 publications

(34 citation statements)

References 99 publications

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“…29,38 IFN-␣ has been used as adjuvant antiangiogenic therapy in neoplasias, 29 diabetic retinopathy, 39 hemangiomas, and Kaposi sarcoma. 28,40 While the exact pathways by which IFN-␣ inhibits angiogenesis are not well characterized and have focused primarily on tumor cell lines, potential mechanisms include VEGF gene transcription inhibition 33 and induction of TRAIL secretion and Fas expression on myelomonocytic cells, with potential angiogenesis impairment via apoptosis. 41,42 In our experiments, neither of these mechanisms accounted for the antiangiogenic effects of IFN-␣ and, given the pleiotropic effects of IFN-␣ on angiogenesis genes, 43 it is likely that the mechanisms are multifactorial.…”

Section: Discussionmentioning

confidence: 99%

Interferon-α promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis

Denny

Thacker

Mehta

et al. 2007

Blood

253

292

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Section: Discussionmentioning

confidence: 99%

Interferon-α promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis

Denny

Thacker

Mehta

et al. 2007

Blood

253

292

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“…Their use in combination with nucleoside inhibitors of HIV reverse transcriptase (highly active antiretroviral therapies) has led to a better clinical outcome in AIDS patients (14). Recent publications suggest that protease inhibitors used in the therapy of HIV-1 patients could have antineoplastic properties through a mechanism of inhibition of the growth of tumor-induced blood vessels, as suggested by the regression of Kaposi sarcomas in HIV-1 human herpes virus 8 -coinfected patients (15 -17).…”

mentioning

confidence: 99%

Evaluation of Antitumoral Properties of the Protease Inhibitor Indinavir in a Murine Model of Hepatocarcinoma

Esposito

Palescandolo

Spugnini³

et al. 2006

Clinical Cancer Research

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Purpose: Accumulating evidences show a higher incidence of hepatic neoplasm in HIV/ hepatitis C virus (HCV)^coinfected individuals compared with HCV-monoinfected patients. Treatment with HIV-1 protease inhibitors inhibited cancer-promoted angiogenesis in HIVinfected patients affected by Kaposi sarcoma. We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models. Experimental Design:We analyzed effects of indinavir on cell growth and invasiveness in Huh7 and SK-HEP-1hepatocarcinoma cell lines and on in vivo tumor growth of the same cells in nude mice. Morphologic and molecular analyses on explanted tumors were carried out to evaluate vascularization and apoptosis. Results: We observed a reduced ability to invade an in vitro extracellular matrix for both cell lines treated with indinavir compared with controls (P = 0,001). Moreover, indinavir treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation, whereas there was no effect on cell proliferation.The drug was also able to delay in vivo tumor growth.The inhibition of tumor growth was statistically significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover, the drug showed antiangiogenic and proapoptotic actions, as revealed by vessel count and apoptotic index by terminal deoxynucleotide transferase^mediated nick end labeling in explanted tumors. Finally, treatment with indinavir did not block the production of vascular endothelial growth factor in the tumors. Conclusion: Indinavir could be helpful to prevent the development of hepatocarcinomas in HIV/HCV^coinfected individuals. In view of the current trend to substitute protease inhibitors with other antiretroviral agents, this information may have clinical implications.

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“…Ideally, a phase III clinical trial comparing all the alternative drugs, including first and second-line, would provide great evidence for treatment choice, however; the low incidence of AIDS-KS caused by the impact of HAART in immune system recovery reduces sample size and interest in studying this condition in USA. Also, since less patients are now progressing to advanced stages of the disease, a less aggressive along with HAART are usually sufficient to treat the early stages of disease and reduce skin lesion, very commonly associated with AIDS and stigmatized by our society [30,33].…”

Section: Chemotherapy Treatment For Ksmentioning

confidence: 99%

A review of the efficacy and outcomes studies of currently approved chemotherapy treatments for advanced AIDS-Kaposi's sarcoma

Raimundo

Asche

2011

HIV & AIDS Review

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a b s t r a c tBackground: Acquired Immune Deficiency Syndrome (AIDS)-related Kaposi's sarcoma (KS) is a rare aggressive tumor. The benefits of drug therapy are established by clinical trials but it has been a challenge to draw comparisons between the different advanced AIDS-KS pharmacotherapy available. This review aims to evaluate the currently approved chemotherapy drugs for the treatment of AIDS-related advanced KS as well as the economic burden and impact on the quality of life of patients. Material and methods: Relevant articles were identified through a systematic review of the literature via a search of the National Center for Biotechnology Information (NCBI) PubMed database and the Internet (clinicaltrials.gov) using relevant medical subject heading (MESH) terms. Results: A total of 7 phase II and 4 phase III trials of liposomal anthracyclines (liposomal doxorubicin [PLD] and/or liposomal daunorubicin [DNX]) were identified. An evaluation of the trials comparing PLD to a competitor showed statistical difference p;0.01. DNX phase III trials were also evaluated and showed no statistical differences (p = 0.64). For paclitaxel, 6 clinical trials were selected (5 phase II and 1 phase III); however heterogeneity was not evaluated. 4 cost-effectiveness studies were compared and 3 concluded that PLD is more cost-effective than the competitor. 4 quality of life studies were analyzed. Conclusion: AIDS-KS impacts the patient's life physical, emotional and economic well being. In this work we compared studies of liposomal anthracyclines, still; further research among all the approved drugs for KS is warranted to evaluate efficacy as well as its economic burden worldwide.

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Treatments of AIDS-related Kaposi's sarcoma

Cited by 49 publications

References 99 publications

Interferon-α promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis

Interferon-α promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis

Evaluation of Antitumoral Properties of the Protease Inhibitor Indinavir in a Murine Model of Hepatocarcinoma

A review of the efficacy and outcomes studies of currently approved chemotherapy treatments for advanced AIDS-Kaposi's sarcoma

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