Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus‐associated Kaposi sarcoma

Abstract

Background Paclitaxel (PTX) and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency (HIV) associated Kaposi’s sarcoma (KS). We performed a randomized trial comparing the efficacy and toxicity of PTX and PLD, and determine the effects of therapy on symptom palliation and quality of life. Methods Patients with advanced HIV-associated KS were randomly assigned to receive PTX (100 mg/m2) IV every 2 weeks, or PLD 20 mg/m2 IV every 3 weeks. The KS Functional Assessment of HIV (FAHI) Quality of Life instrument was used before and after every other treatment cycle. Results The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the PTX arm and 37 in the PLD arm; 73% received highly active antiretroviral therapy (HAART) and 32% had undetectable viral load (<400 copies/mL). Treatment was associated with significant improvement in pain (P=0.024) and swelling (P<0.001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the PTX and PLD arms revealed comparable response rates (56% vs. 46%; p=0.49), median progression free survival (17.5 vs. 12.2 months; p=0.66), and 2-year survival (79% vs. 78%; p=0.75), but somewhat more grade 3–5 toxicity for PTX (84% vs. 66%, p=0.077). Conclusion Treatment with either PTX or PLD produces significant improvement in pain and swelling in patients with advanced, symptomatic, HIV-associated KS treated in the early HAART era.

A review of the efficacy and outcomes studies of currently approved chemotherapy treatments for advanced AIDS-Kaposi's sarcoma

“…They authors concluded that either paclitaxel or PLD leads to improvement in symptoms of AIDS-KS including pain and difficulty swelling. Also, in accordance to their previous published work [21], the two studied drugs are active to treat AIDS-KS even in an HAART era [31]. .…”

“…Von Roenn et al [21], conducted a phase III clinical trial comparing paclitaxel and liposomal doxorubicin for the treatment of advanced AIDS-KS where they found no statistical difference in efficacy, however; the study was terminated early due to slow accrual and difficulties in recruitment ( Table 2). Later in 2010, the same group published more results of the trial including data on quality of life [31]. They authors concluded that either paclitaxel or PLD leads to improvement in symptoms of AIDS-KS including pain and difficulty swelling.…”

Pulmonary manifestations of human herpesvirus-8 during HIV infection

“…Anthracyclines are well tolerated despite the risk of cardiac toxicity; response rates are almost 50%, with a median of 5 months response [57]. Chemotherapy with paclitaxel shows almost the same efficacy but can interact with protease inhibitors [58,59]. Protease inhibitors, such as ritonavir, are among the most potent antiviral drugs and are often a component of cART [60].…”

“…The easiest alternative is to switch the protease inhibitor for another antiviral drug; if necessary, paclitaxel and a protease inhibitor may be associated, with close monitoring [63]. Bleomycin and vinblastine show poor response when used as monochemotherapy and are usually combined with pegylated liposomal doxorubicin [59]. Furthermore, chemotherapy induces additional immunodeficiency, which necessitates prophylaxis against pneumocystosis and toxoplasmosis.…”

HIV-Associated Kaposi's Sarcoma

“…However, according to a small randomized study that was not sufficiently powered, it appears to be slightly less effective than pegylated liposomal doxorubicin [21]. Another option is paclitaxel, which has shown similar response rates in a small randomized trial on patients with advanced KS [22]. However, paclitaxel is more myelotoxic and almost always leads to complete alopecia, often during the very first cycle.…”