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 University of Southern California School of Medicine, reported that DaunoXome produces significant improvement in Kaposi's sarcoma (KS) lesions that have penetrated the lungs. In a new clinical trial involving 35 patients with pulmonary KS, 15 (43%) showed complete or partial resolution of symptoms. Another 17 patients (49%) realized some benefit from DaunoXome treatment.
Kaposi's sarcoma lesions penetrate the lungs of up to 47% of patients and are potentially life-threatening. Dr. Gill was the principal investigator of DaunoXome's US phase III clinical trial for advanced HIV-associated KS.
Geoffrey M. Mukwaya, MD, a member of NeXstar's clinical staff, presented pharmacokinetic data from phase II and III clinical trials in advanced HIV-associated KS. These data showed that DaunoXome is cleared from the bloodstream more slowly than free daunorubicin(Drug information on daunorubicin). This longer circulation half-life of DaunoXome allows for greater concentration of daunorubin in tumors than is otherwise possible with free drug. However, circulation half-life is not long enough to produce side effects associated with continuous infusion of anthracycline 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 III clinical trial in which DaunoXome was compared to the standard three-drug regimen ABV (Adriamycin, bleomycin(Drug information on bleomycin), and vincristine) as a therapy for advanced HIV-associated KS. The phase III data showed that DaunoXome is as effective as ABV, yet produces significantly fewer of the side effects that adversely affect a patient's quality of life. For example, alopecia occurred in 8% of patients treated with DaunoXome, compared with 36% of the patients who received ABV. Similarly, only 13% of those treated with DaunoXome experienced neuropathy, 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 time to treatment failure was also longer for DaunoXome-treated patients than for ABV-treated patients (115 vs 99 days).
Lack of Long-Term Cardiotoxicity
In Dr. Gill's second presentation, he said that there is less cardiotoxicity seen after long-term DaunoXome therapy. Normally, cardiotoxicity is the chief treatment-limiting side effect associated with anthracycline chemotherapy, and its incidence increases exponentially after cumulative doses of 500 mg/m2. In studies involving 277 patients receiving DaunoXome-therapy for advanced HIV-associated KS, 53 received cumulative doses totaling over 600 mg/m², and none of these patients showed signs of anthracycline-induced cardiotoxicity. Of the 53 patients, 34 received between 600 and 999 mg/m², 12 received between 1,000 and 1,499 mg/m2, and 7 received more than 1,500 mg/m².
"Taken together, these four presentations demonstrate DaunoXome's novel therapeutic profile, both in terms of efficacy and safety," said Michael E. Ross, md, NeXstar's Vice-President for Medical and Regulatory Affairs. "The lack of cardiac toxicity seen at doses more than three-fold higher than the normal safe level of anthracycline therapy is particularly exciting. Being able to give high cumulative doses of DaunoXome bodes well not only for the long-term safety of DaunoXome therapy in the treatment of advanced HIV-associated KS, but also for potential utility in the aggressive treatment of other cancers known to respond to anthracycline therapy, such as breast cancer, lymphoma, leukemia and small-cell lung cancer."