ABSTRACT
Acknowledgment ................................................................................................................. 277
References ........................................................................................................................... 278
I. INTRODUCTION Kaposi' s sarcoma (KS) is the most frequent opportunistic neoplasm encountered in patients
with acquired immunodeficiency syndrome (AIDS). About 20% of HIV -infected homosexual men present with KS as an index diagnosis of AIDS.l.2 Complications of AIDS-related KS depend primarily on the stage of the disease and its pattern of clinical manifestations (cutaneous vs. visceral). Gastrointestinal and pulmonary KS are potentially life threatening. Complications such as bleeding, ileus, and respiratory failure contribute to morbidity and mortality caused by KS. Edema of face or limbs occurs along with more severe categories of KS. Several different antitumor chemotherapeutic agents have been used as systemic intervention forKS when chemotherapy was indicated.3 Vinca alkaloids, doxorubicin, and bleomycin have been administered in several trials, either as a single agent or in different combinations.3· 8 Neither single-agent therapy nor any combination treatment has been satisfactory enough to be regarded as "standard" in systemic advanced KS. Although combinations such as doxorubicin,
bleomycin, and vincristine (ABV) provide comparably high response rates, this regimen results in considerable toxicity and complication rates (about 60% of patients developed opportunistic infection following ABV therapy).7•9
Conventional doxorubicin used as a monotherapy at a dose of 15 mg/m2 weekly resulted in a 10% partial response with no complete remissions being reported.w Pharmacologic data have been reported for Stealth liposomal encapsulated doxorubicin (DOX-SL™) showing long plasma half-life, an increased accumulation in tumor tissue compared with the same dose of free doxorubicin, and a decreased uptake by tissues such as liver, spleen, and bone marrow. 1H 3 In animal models it has been reported that the prolonged circulation time of DOX-SL correlates with superior therapeutic effectiveness.li We have used DOX-SL to treat patients with advanced KS in an open dose-escalating trial. Our objectives were to evaluate efficacy and toxicity of DOX-SL and to evaluate whether results of a first Phase 1/II trial would justify randomized trials comparing it to more traditional combination regimens.
