DaunoXome Data Presented at International Cancer Meeting

June 1, 1996

NeXstar Pharmaceuticals made four DaunoXome-related presentations at the 9th NCI-EORTC Symposium on New Drugs in Cancer Therapy in Amsterdam, The Netherlands. Parkash S. Gill, MD, associate professor medicine and pathology at the

NeXstar Pharmaceuticals made four DaunoXome-related presentationsat the 9th NCI-EORTC Symposium on New Drugs in Cancer Therapyin Amsterdam, The Netherlands. Parkash S. Gill, MD, associateprofessor medicine and pathology at the University of SouthernCalifornia School of Medicine, reported that DaunoXome producessignificant improvement in Kaposi's sarcoma (KS) lesions thathave penetrated the lungs. In a new clinical trial involving 35patients with pulmonary KS, 15 (43%) showed complete or partialresolution of symptoms. Another 17 patients (49%) realized somebenefit from DaunoXome treatment.

Kaposi's sarcoma lesions penetrate the lungs of up to 47% of patientsand are potentially life-threatening. Dr. Gill was the principalinvestigator of DaunoXome's US phase III clinical trial for advancedHIV-associated KS.

Geoffrey M. Mukwaya, MD, a member of NeXstar's clinical staff,presented pharmacokinetic data from phase II and III clinicaltrials in advanced HIV-associated KS. These data showed that DaunoXomeis cleared from the bloodstream more slowly than free daunorubicin.This longer circulation half-life of DaunoXome allows for greaterconcentration of daunorubin in tumors than is otherwise possiblewith free drug. However, circulation half-life is not long enoughto produce side effects associated with continuous infusion ofanthracycline anticancer agents.

Theory for Advanced HIV-Associated KS

Dr. Gill made two other presentations at the Amsterdam meeting.The first summarized the results of the US randomized phase IIIclinical trial in which DaunoXome was compared to the standardthree-drug regimen ABV (Adriamycin, bleomycin, and vincristine)as a therapy for advanced HIV-associated KS. The phase III datashowed that DaunoXome is as effective as ABV, yet produces significantlyfewer of the side effects that adversely affect a patient's qualityof life. For example, alopecia occurred in 8% of patients treatedwith DaunoXome, compared with 36% of the patients who receivedABV. Similarly, only 13% of those treated with DaunoXome experiencedneuropathy, compared with 41% of those treated with the ABV regimen.In addition, median survival for DaunoXome patients was 366 days,compared with 338 days for those treated with ABV. Median timeto treatment failure was also longer for DaunoXome-treated patientsthan for ABV-treated patients (115 vs 99 days).

Lack of Long-Term Cardiotoxicity

In Dr. Gill's second presentation, he said that there is lesscardiotoxicity seen after long-term DaunoXome therapy. Normally,cardiotoxicity is the chief treatment-limiting side effect associatedwith anthracycline chemotherapy, and its incidence increases exponentiallyafter cumulative doses of 500 mg/m2. In studies involving 277patients receiving DaunoXome-therapy for advanced HIV-associatedKS, 53 received cumulative doses totaling over 600 mg/m²,and none of these patients showed signs of anthracycline-inducedcardiotoxicity. Of the 53 patients, 34 received between 600 and999 mg/m², 12 received between 1,000 and 1,499 mg/m2, and7 received more than 1,500 mg/m².

"Taken together, these four presentations demonstrate DaunoXome'snovel therapeutic profile, both in terms of efficacy and safety,"said Michael E. Ross, md, NeXstar's Vice-President for Medicaland Regulatory Affairs. "The lack of cardiac toxicity seenat doses more than three-fold higher than the normal safe levelof anthracycline therapy is particularly exciting. Being ableto give high cumulative doses of DaunoXome bodes well not onlyfor the long-term safety of DaunoXome therapy in the treatmentof advanced HIV-associated KS, but also for potential utilityin the aggressive treatment of other cancers known to respondto anthracycline therapy, such as breast cancer, lymphoma, leukemiaand small-cell lung cancer."