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A pilot study of cidofovir in patients with kaposi sarcoma
Richard F Little1, Florentino Merced-Galindez, Katherine Staskus
1HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Abstract:
A clinical trial was conducted to test the activity of cidofovir (CDV), a drug with in vitro activity against Kaposi sarcoma (KS)-associated herpesvirus (KSHV), in KS. Five patients with human immunodeficiency virus-associated KS (4 receiving antiretroviral therapy) and 2 patients with classical KS were administered CDV (5 mg/kg/dose) weekly for 2 weeks and then every other week. All 7 patients had progression of their KS at a median of 8.1 weeks (range, 5-27 weeks). Skin biopsy specimens of KS lesions showed no change in expression of latent or early lytic genes, but, in the 1 assessable patient, there was decreased expression of a late lytic gene. There was no decrease in the virus load of KSHV in peripheral blood mononuclear cells. This study does not provide proof of principle for the treatment of KS with CDV. However, it remains possible that antiherpesvirus therapy can be developed for herpes-induced tumors.
Insights
Cidofovir (CDV) did not effectively treat Kaposi sarcoma (KS) in a clinical trial, as all patients experienced disease progression. Further research into antiherpesvirus therapies for tumors like KS is still warranted.
Area of Science:
- Oncology
- Virology
- Pharmacology
Background:
- Kaposi sarcoma (KS) is a cancer associated with human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV).
- Cidofovir (CDV) exhibits in vitro activity against KSHV, suggesting potential therapeutic application in KSHV-associated malignancies.
Purpose of the Study:
- To evaluate the clinical activity of cidofovir (CDV) in patients with Kaposi sarcoma (KS).
Main Methods:
- A clinical trial administered weekly cidofovir (CDV) at 5 mg/kg/dose for two weeks, followed by bi-weekly dosing.
- The study included seven patients: five with HIV-associated KS and two with classical KS.
- Tumor biopsies and peripheral blood mononuclear cells were analyzed for viral gene expression and KSHV viral load.
Main Results:
- All seven patients showed progression of Kaposi sarcoma (KS) at a median of 8.1 weeks.
- No significant changes were observed in latent or early lytic KSHV gene expression in KS lesions.
- One patient showed decreased late lytic gene expression; KSHV viral load in peripheral blood mononuclear cells remained unchanged.
Conclusions:
- This study did not establish proof of principle for using cidofovir (CDV) to treat Kaposi sarcoma (KS).
- The findings suggest that while CDV may not be effective, antiherpesvirus therapies could potentially be developed for KSHV-induced tumors.