Phase III study of paclitaxel (Pac) versus pegylated liposomal doxorubicin (PLD) for the treatment of advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS): An Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium

Abstract

20503 Background: PLD (doxorubicin HCL liposome injection, Doxil®, Tibotec Therapeutics, Raritan, NJ) and paclitaxel (Taxol®, Bristol Myers, Inc, New York, NY) are active in the treatment of HIV-associated KS; however, optimal therapy is undefined. Methods: A randomized phase III, multicenter trial was initiated to compare the efficacy of Pac (100 mg/m2) every 2 weeks to PLD (20 mg/m2) every 3 weeks for chemotherapy-naïve AIDS-related KS. Treatment continued until disease progression or unacceptable toxicity; concurrent antiretrovirals were permitted. 216 pts were required to detect at least a 3-month improvement in median progression free survival (PFS) for Pac compared with PLD (80% power, 2-sided alpha 0.05). Response was assessed using KS response and clinical benefit criteria, and global assessment of quality of life (QOL) using the Functional Assessment of Health Index (FAHI; version 3) plus 3 supplemental questions concerning pain, swelling, and satisfaction with physical appearance (measured at baseline and during/after treatment). Results: The trial was terminated early due to poor accrual; 46 pts were randomized to PLD, 43 to Pac. 11 pts were ineligible, 4 never started therapy and 6 lacked disease assessment or progression data, resulting in 68 pts for the efficacy analysis (34 in each arm) and 82 in the toxicity analysis. After a median follow-up of 35.8 months (mo.), there was no significant difference in PFS, response rate, or overall survival. Due to early termination, the study was not adequately powered to detect the hypothesized difference in PFS. There was no significant difference in QOL between the two arms. Grade 3–4 toxicity was comparable, including grade 4 neutropenia (34% vs. 27%) and infection (13% vs. 11%). Conclusions: Paclitaxel and PLD have comparable efficacy and toxicity in patients with HIV-associated KS. [Table: see text] [Table: see text]