Results of a Clinical Pharmacokinetic (PK) Bioequivalence (BE) Study of Liposomal Paclitaxel (LEP-ETU) Versus Paclitaxel (T) in Patients with Advanced Cancer

2017 Background: LEP-ETU is an easy-to-use liposomal formulation of paclitaxel developed to reduce toxicities associated with the excipient polyoxyethylated castor oil that is used in paclitaxel (Taxol [T]), while maintaining or enhancing efficacy. A phase I study of LEP-ETU demonstrated an MTD of 325 mg/m2 and a similar PK profile at a dose of 175 mg/m2 compared to published T data (Damjanov et al, J Clin Oncol 2005;23 Suppl:147s). Methods: This randomized, two-period crossover, clinical BE study was designed to directly compare the PK of paclitaxel following intravenous administration of LEP-ETU and T delivered over 180 minutes at a dose of 175 mg/m2 in patients with a variety of advanced solid tumors. Patients were randomized to receive either one treatment cycle of LEP-ETU followed by one cycle of T, or one cycle of T followed by one cycle of LEP-ETU. Eligible patients were permitted to continue LEP-ETU treatment in an extension study. Results: Fifty-eight patients were treated, and 32 evaluable patients were analyzed for BE. The latter group of patients met pre-specified evaluability criteria of having received 100% of each dose during the specified administration interval and having had the necessary blood samples drawn to determine Cmax and AUC. Mean total paclitaxel Cmax values for LEP-ETU and T were 4955.0 ng/mL and 5108.8 ng/mL, respectively. Mean total paclitaxel AUC0–8 values for LEP-ETU and T were 15853.8 ng·h/mL and 18550.8 ng·h/mL, respectively. Ratios of the geometric means of LEP-ETU divided by T for Cmax were 97% (90% CI, 91%-103%) and for AUC0–8 were 84% (90% CI, 80%-90%). These results meet the established 80–125% BE criteria. The most frequently reported adverse events were fatigue, alopecia, and myalgia. Of the 37 patients deemed suitable to continue LEP-ETU treatment in the extension study, 57% have received = 4 cycles of LEP-ETU with at least stable disease. Conclusion: LEP-ETU has met BE criteria compared to T. A comparative efficacy and safety study of LEP-ETU and T at a dose of 175 mg/m2 has been planned to confirm the potential of LEP-ETU to have comparable or improved treatment effect with a better safety profile than T. [Table: see text]