PHASE I II CLINICAL AND PHARMACOKINETIC EVALUATION OF LIPOSOMAL DAUNORUBICIN/

Purpose: Since liposomal encapsulation of anticancer drugs may enhance antitumor activity while reducing toxicity in vitro, we evaluated lip osomally encapsulated daunorubucin (Dauno Xome; Vestar, Inc, San Dimas , CA) for safety, pharmacokinetics, and potential efficacy in patients with AIDS-related Kaposi's sarcoma (AIDS-KS). Patients and Methods: F orty patients with advanced AIDS-KS were accrued. Successive cohorts r eceived DaunoXome at doses of 10, 20, 30, and 40 mg/m(2) given once ev ery 3 weeks, and 40, 50, and 60 mg/m(2) given once every 2 weeks. Sele cted KS and solid-tumor patients underwent pharmacokinetic evaluation. Results: The area under the plasma concentration curve (AUG) ranged f rom 16.9 mu g.h/mL to 375.3 mu g./mL and the alpha half-life ranged fr om 7.8 to 8.3 hours at 10 mg/m(2) to 60 mg/m(2), respectively. Both ph armacokinetic profiles were significantly better compared with free da unorubicin. DaunoXome was well tolerated with no significant alopecia, mucositis, or vomiting. Neutropenia (< 1,000/mu L) occurred in 17% of cycles and was severe (< 500/mu L) in only 2%. Anemia and thrombocyto penia were uncommon. Other adverse events included mild to moderate fa tigue, nausea, and diarrhea. Even after cumulative doses greater than 1,000 mg/m(2), no significant declines in cardiac function were observ ed. Twenty-two patients who received 50 and 60 mg/m(2) were assessable for tumor response; 12 (55%) had a partial response (PR) or clinical complete response (CR). The median survival duration in all patients w as 9 months. Prognostic factors for short survival were low CD4 lympho cyte counts (P = .004) and prior anthracycline therapy (P = .02). Conc lusion: DaunoXome has an improved pharmacokinetic profile compared wit h free daunorubicin, and is well tolerated. DaunoXome con be given saf ely at doses up to 60 mg/m(2) every 2 weeks and has significant antitu mor activity in patients with AIDS-KS. J Clin Oncol 13:996-1003. (C) 1 995 by American Society of Clinical Oncology.