BACKGROUND The objective of this study was to compare the efficacy and toxicity of the liposome‐encapsulated doxorubicin, TLC D‐99 (Myocet, Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in first‐line treatment of metastatic breast carcinoma (MBC). METHODS Two hundred twenty‐four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D‐99 (75 mg/m2) or doxorubicin (75 mg/m2) every 3 weeks, in the absence of disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate. Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks' duration. The primary safety endpoint was cardiotoxicity. Cardiac function was monitored by multiple‐gated radionuclide cardioangiography scan, and the left ventricular ejection fraction (LVEF) was scored at a central laboratory. Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50%, or by 10 or more units to a final value of less than 50%, or onset of clinical congestive heart failure (CHF). RESULTS Median age was 54 years in both treatment groups. All relevant prog nostic factors were balanced, with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin‐treated group. Protocol‐defined cardiotoxicity was observed in 13% of TLC D‐99 patients (including 2 cases of CHF) compared to 29% of doxorubicin patients (including 9 cases of CHF). Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m2 for TLC D‐99 versus 570 mg/m2 for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall response rate was 26% in both treatment groups. The median TTP was 2.9 months on TLC D‐99 versus 3.1 months on doxorubicin. Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin (P = 0.09). Clinical toxicities, commonly associated with doxorubicin, appeared less common with TLC D‐99, although the difference was not statistically significant. There was only one report of palmar‐plantar erythrodysesthesia (Grade 2) with this liposomal formulation of doxorubicin. CONCLUSIONS Single‐agent TLC D‐99 produces less cardiotoxicity than doxorubicin, while providing comparable antitumor activity. Cancer 2002;94:25–36. © 2002 American Cancer Society.

Oral thalidomide was tolerated in this population at doses up to 1,000 mg/d for as long as 12 months and was found to induce clinically meaningful anti-KS responses in a sizable subset of the patients. Additional studies of this agent in KS are warranted.

Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease.