Kaposi's Sarcoma Advances Include New Gel, PDT, More

September 1, 1996

VANCOUVER, BC--Discussions of Kaposi's sarcoma at the 11th International Conference on AIDS included reports on a promising topical treatment, photodynamic therapy (PDT), a chemotherapy regimen that could save up to $1,000 per course, and the possibility of prevention using antiherpes drugs.

VANCOUVER, BC--Discussions of Kaposi's sarcoma at the 11th InternationalConference on AIDS included reports on a promising topical treatment,photodynamic therapy (PDT), a chemotherapy regimen that couldsave up to $1,000 per course, and the possibility of preventionusing antiherpes drugs.

A retinoid gel shows promise of becoming the first topical therapyfor Kaposi's sarcoma (KS), said Madeleine Duvic, MD, chief, DermatologySection, University of Texas M.D. Anderson Cancer Center.

In a phase I/II clinical trial, the 9-cis-retinoic acid (ALRT1057, being developed by Ligand Pharmaceuticals Inc., San Diego)proved safe and well tolerated. And although the trials was notdesigned to evaluate efficacy, the researchers found that thegel produced complete resolution of lesions in 9% of patientsand resolution of at least half of lesions in 23%.

Importantly, responses were seen in patients with a wide rangeof CD4 counts, including four patients with counts below 50 cells/mm3.Dr. Duvic suggested that the retinoid gel may make possible aform of "patient-controlled, conservative management"in the early phases of KS.

This multicenter study enrolled 63 patients with biopsy proven,multiple KS lesions. Patients applied the gel to selected indexlesions one to four times daily. Similar control lesions wereleft untreated (but could be treated after 8 to 16 weeks). Forty-threepatients with 179 treated index lesions and 119 control lesionsreceived at least 12 weeks of therapy (or had withdrawn priorto 12 weeks).

Responses Hard to Evaluate

Response in KS lesions has been notoriously hard to evaluate becausethe area of pigmentation associated with the lesion may not shrinkeven though response is demonstrable histopatholog-ically, Dr.Duvic said. This study used methodology developed by the AIDSClinical Trials Group, to evaluate response by measuring areaand elevation of the lesion.

Partial responses for treated lesions occurred in 13 patients(30%) vs 4 (9%) for control lesions. A complete flattening ofat least 50% of raised lesions was achieved in 26% of the treatedgroup vs 9% in the control group, and a 50% or greater decreasein the sum of the area of lesions occurred in 7% of the treatedgroup but in none of the control group.

"One or more lesions responded in 30% of patients,"Dr. Duvic said. Responses were sustained for a median follow-upof 16 weeks; only 4 of 28 lesions had relapsed after a medianof 12 weeks.

Photodynamic therapy with the investigational agent tin ethyletiopurpurin (SnET2, being developed by PDT, Inc., Santa Barbara,Calif) had a positive effect on KS skin lesions, particularlypapular stage KS, in studies at the U. of California, San Francisco,said Roy Grekin, MD, chief of dermatologic surgery.

In these phase I/II clinical trials, Dr. Grekin and his colleaguestreated 29 patients with 172 skin lesions using various drug andlight combinations. They found that a therapeutic dose of SnET2at 1.2 mg/kg with light irradiation at 300 J/cm² produceda response rate of 87% among papular stage KS lesions and 41%among macular stage KS lesions.

UCSF is now participating in PDT, Inc.'s multicenter phase II/IIIpivotal clinical trials of photodynamic therapy for KS, whichstarted last March.

Although the drug cost of treatment with DaunoXome (liposomaldaunoru-bicin) for advanced HIV-associated KS is slightly higherthan that of the standard three-drug ABV regimen (Adriamycin,bleomycin, vincristine), the total cost to administer a standardcourse of therapy is approximately 10% less for Dauno-Xome, GaleE. Savage, MD, said at the AIDS conference. The savings per courseof treatment (eight cycles over 16 weeks) came to $974.

Less Expensive to Administer

The pharmacoeconomic analysis by Dr. Savage, clinical managerin health economics with S&FA, Inc., in Alexandria, Virginia,included the costs of the chemotherapy drugs, drug administration,monitoring costs, and managing side effects.

Using this four-factor model and data from the pivotal phase IIIclinical trial of DaunoXome, Dr. Savage found that DaunoXome,because it is a single therapy as opposed to combined therapy,was less than half as expensive to administer as ABV therapy.Although some Dauno-Xome patients required more growth factors,this cost was more than offset by a drop in the costs associatedwith monitoring for side effects, Dr. Savage said.

The discovery in 1994 that a herpesvirus (known as human herpesvirus-8,HHV8, or KS-associated herpesvirus, KSHV) is involved in causingHIV-related KS immediately raised the question of possible preventionusing currently available antiherpes drugs.

This approach has now been studied retrospectively by the RoyalFree Hospital and Westminster Hospitals Collaborative Group, London."Both foscarnet and ganciclovir may have some activity inpreventing the occurrence of Kaposi's sarcoma," Amanda Mocroft,MSc, said at the conference.

The London investigators assessed the association between treatmentwith acyclovir (Zovirax), foscarnet (Foscavir), and ganciclovir(Cytovene) and risk of KS in 3,688 patients with HIV followedfor a median of 4.2 years.

Sixteen percent of patients (598) developed KS during the 4-yearperiod. The risk of developing KS was significantly lower in patientswho had been treated with foscarnet or ganciclovir. Risk was notdecreased by treatment with acyclovir.

The lower risk of developing KS associated with foscarnet or ganciclovirtreatment remained after the researchers adjusted for gender,exposure category, age, antiretroviral treatment, PCP prophylaxis,CD4 count, and development of AIDS-defining conditions, includinga separate adjustment for the development of cytomegalovirus orherpes simplex, Ms. Mocroft said. "Further studies of theantiviral effect of these drugs are clearly warranted," sheconcluded.