Phase I study of liposome entrapped paclitaxel (LEP-ETU) in patients with advanced cancer

2110 Background: The rationale for developing a liposomal formulation of paclitaxel is to improve the safety profile by eliminating toxicities associated with the drug formulation component, polyoxyethylated castor oil (Cremophor® EL), while maintaining or enhancing efficacy. This phase I study is designed to determine the MTD, DLT, and pharmacokinetics of LEP-ETU, an easy to use formulation of liposome entrapped paclitaxel, in patients with advanced cancers. Methods: Adult patients with incurable solid tumors receive intravenous LEP-ETU infusion over 90 minutes every 21 days until disease progression or unacceptable toxicity occurs. Dose escalation is planned with separate patient cohorts receiving 135 to 325 mg/m2 of LEP-ETU. Patients are monitored closely for any neurological changes and for tumor progression. Results: As of 16 December 2003, ten patients have received doses of 135 mg/m2 (n=3), 175 mg/m2 (n=4), or 225 mg/m2 (n=3). In the 6 men and 4 women enrolled, ages ranged from 23–80 years (median 65), and ECOG PS ranged from 0–2. Among the primary cancers were colon, breast, and pancreatic. Patients have completed up to 6 treatment cycles (median 2.5). To prevent infusion-related reactions (IRRs), patients have been premedicated on the day of infusion. In 25 of 26 such treatment cycles breakthrough IRRs have not occurred. Therefore, to assess whether premedication is clinically necessary, it is no longer required. No IRRs occurred in the single patient treated (225 mg/m2) without premedication to date. In the 225 mg/m2 cohort, 1 patient had Grade 2 neutropenia, and another had Grade 1 neuropathy, with both considered possibly related to study drug. No neutropenia or neuropathy considered related to study drug have occurred at the lower dose levels. No DLTs and no SAEs considered related to drug have been reported. Mean drug concentration versus time curves for the 135 and 175 mg/m2 cohorts parallel those reported for similar doses of paclitaxel/Cremophor EL. Conclusions: Patient accrual and dose escalation without premedication are continuing beyond the standard paclitaxel dose. At the doses administered thus far, LEP-ETU appears to be safe and well tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NeoPharm, Inc.