Cancer Treatment Today

VISTIDE (cidofovir) is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). The FDA says: “THE SAFETY AND EFFICACY OF VISTIDE (cidofovir) HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER CMV INFECTIONS (SUCH AS PNEUMONITIS OR GASTROENTERITIS), CONGENITAL OR NEONATAL CMV DISEASE, OR CMV DISEASE IN NON-HIV-INFECTED INDIVIDUALS.”

It is a nephrotoxoc drug and cannot be administered to people with kidney dysfunction, which, however, is common after stem cell transplantation or aggressive chemotherapy. Therefore, some attempt to reconstitute the IV formulation and use it topically. It is a water-soluble polar molecule and is predicted to be absorbable across the gastrointestinal tract following oral administration although. No oral formulations are currently available and bioavailability studies have been performed to a limited extent only in animals. It has been compounded in bases for topical use although topical formulations are prohibitively expensive (approximately $65 US per gram of extemporaneously compounded 3% cidofovir cream or it can be compounded as a 1% solution. There are case reprots of using these preparations for condyloma acumina, veruca vulgaris, laryngeal papillomatosis, Kaposi’s sarcoma, poxvirus infections and herpetic infections.

De Clercq and Holy demonstrated that topical cidofovir was effective against human herpesvirus types 1 and 2 and thymidine kinase deficient herpesvirus type 1 in mice. They demonstrated that its efficacy was superior to acyclovir. Snoeck et al reported successful the use of topical cidofovir in 2 patients, one with AIDS and the othe, a bone amrrow transplant patient,  with resistant herpesvirus infections. Lateef et al used a topical preparation for a 4-year-old child with AIDS and a large facial ulcer secondary to herpesvirus type 1. Other case reprots were published by C.R.SIms in 2007, B. Muluneh in 2012

Lalezari et al reported a randomized, double blind, placebo controlled phase I/II clinical study of cidofovir gel in 30 patients with AIDS, all of whom had acyclovir-resistant herpes simplex infections. Eleven patients received 0.3% gel, nine patients received 1.0% gel and 10 were treated with placebo once a day for 5 days. Fifty percent of cidofovir patients had at least 50% improvement in infection in contrast with no improvement in the placebo patients. Thirty percent of the cidofovir treated patients had complete healing, compared with none of the placebo treated patients. The median time for negative viral cultures to be obtained from lesions in the cidofovir treated group was 2 days. Eighty seven per cent of CDV treated patients and no placebo treated patients developed negative viral cultures. Application site reactions occurred in 25 % of cidofovir-treated patients and in 20% of placebo-treated patients. Of the 6 patients treated with CDV who had complete healing, the response was sustained in 3.

Sacks et al described the successful use of cidofovir topical gel in otherwise healthy patients with recurrent genital herpes infection. Ninety-six patients were randomized in a double blind, placebo controlled trial. All patients were confirmed by viral culture or serology as having recurrent genital herpes simplex. Treatment consisted of a single application of cidofovir gel 1%, 3%, 5% or placebo within 12 hours of an outbreak. All patients treated with cidofovir showed a decrease both in median time for cultures to become negative and in the number of days to complete healing. Sacks et al concluded that topical cidofovir gel was well tolerated and possessed significant antiviral activity.

In conclusion, there a a number of case reports and series that support this drug, as well as two Phase II studies, one randomized. 1%, 3% and 5% solutions have shown activity.
Edward J. Zabawski,  Review of Topical and Intralesional Cidofovir
Jr.Dermatology Online Journal 6(1): 3, 2000

De Clercq E. Therapeutic potential of Cidofovir (HPMPC, Vistide) for the treatment of DNA virus (i.e. herpes-, papova-, pox- and adenovirus) infections. Verh K Acad Geneeskd Belg 1996;58(1):19-47; discussion 47-9.

Snoeck R, Andrei G, Gerard M, Silverman A, Hedderman A, Balzarini J, Sadzot-Delvaux C, Tricot G, Clumeck N, De Clercq E. Successful treatment of progressive mucocutaneous infection due to acyclovir- and foscarnet-resistant herpes simplex virus with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). Clin Infect Dis 1994;18(4):570-8.

Lateef F, Don PC, Kaufmann M, White SM, Weinberg JM. Treatment of acyclovir-resistant, foscarnet-unresponsive HSV infection with topical cidofovir in a child with AIDS [letter; comment] Arch Dermatol 1998;134(9):1169-70.

Lalezari J, Schacker T, Feinberg J, Gathe J, Lee S, Cheung T, Kramer F, Kessler H, Corey L, Drew WL, Boggs J, McGuire B, Jaffe HS, Safrin S. A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS. J Infect Dis 1997;176(4):892-8.

Sacks SL, Shafran SD, Diaz-Mitoma F, Trottier S, Sibbald RG, Hughes A, Safrin S, Rudy J, McGuire B, Jaffe HS. A multicenter phase I/II dose escalation study of single-dose cidofovir gel for treatment of recurrent genital herpes. Antimicrob Agents Chemother 1998;42(11):2996-9.

Sims CR, Thompson K, Chemaly RF, Shpall EJ, Champlin RE, Safdar A. Oral topical cidofovir: novel route of drug delivery in a severely immunosuppressed patient with refractory multidrug-resistant herpes simplex virus infection.Transpl Infect Dis. 2007 Sep;9(3):256-9.

B. Muluneh et al, Successful clerance of acyclovir resistant, foscarnet refractory herpes virus lesions with topical cidifivit in allogneic hematoppoietic stem cell transplant patient, J Oncol Pharm Pract, published online 24 May 2012

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