A phase I trial of ABI-007, nanoparticle paclitaxel, administered to patients with advanced non-hematologic malignancies

Abstract

2027 Background: To evaluate the safety/tolerability, maximum tolerated dose (MTD), and anti-tumor effect of nanoparticle paclitaxel (ABI-007). This novel Cremophor-free formulation was administered intravenously during weekly monotherapy to patients with advanced non-hematologic malignancies. This single center, Phase I, open-label study also evaluated the pharmacokinetic profile of ABI-007. Methods: Thirty nine patients were enrolled and received doses of ABI-007 ranging from 80 mg/m2/day to 200 mg/m2/day as a 30 minute IV infusion once a week for 3 weeks followed by a week of rest. A standard “3+3” design was used for dose escalation. Patients were divided into 2 groups, those who had been heavily pre-treated (HP) with prior anti-neoplastic therapy and those who had not (LP). Results: Thirty-nine patients were treated with >169 courses (3 cycles/course) of ABI-007. There were no hypersensitivity reactions to this formulation. The DLT in this trial for HP patients was grade 4 neutropenia and grade 3 peripheral neuropathy for LP patients. The MTD for HP patients is 100 mg/m2. The MTD for LP patients is 150 mg/m2. Other toxicities reported included fatigue, nausea/vomiting, mild anemia, and alopecia. To date, 5 patients have had a partial response including one with lung cancer (4 mos.), one with breast cancer (7mos.), and three with ovarian cancer (13 mos., 10 mos., and 4 mos.). These patients all had prior therapy with paclitaxel. Over the dose range of 80–150 mg/m2, the range of mean values for plasma clearance was 22–31 L/hr/m2, the means for plasma half-life were 15–18 hr, and the means for apparent volume of distribution were 549–772 L/m2. Pharmacokinetic analyses of ABI-007 exhibited linear increases for Cmax and area under the curve (AUC). Conclusion: Our results indicate that ABI-007 can be given safely on a weekly schedule without premedication for possible anaphylaxis and with minimum toxic side effects. Antitumor activity has been documented in patients with lung, ovarian, and breast cancer, and in patients who have had prior taxane therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American BioSciences, Inc.