Phase I and Pharmacokinetic Study of ABI-007, Albumin-bound Paclitaxel, Administered Every 3 Weeks in Japanese Patients with Solid Tumors

OBJECTIVE: ABI-007 is a novel Cremophor(®) EL-free nanoparticle albumin-bound paclitaxel. This Phase I study was designed to evaluate tolerability and determine recommended dose for Japanese patients when ABI-007 was administered in every-3-week schedule. Pharmacokinetics of paclitaxel was also assessed. METHODS: Patients with advanced solid tumors refractory to standard therapy received a 30 min intravenous infusion of ABI-007 every 3 weeks without pre-medications at 200, 260 or 300 mg/m(2), respectively. Tolerability and recommended dose were determined by the standard ‘3 + 3’ rule. RESULTS: No dose-limiting toxicity was observed, despite the dose escalation. In another cohort, 260 mg/m(2) was re-evaluated and resulted in no dose-limiting toxicity. Grade 3 or 4 neutropenia was reported for the majority of patients (n = 8) but no incidence of febrile neutropenia. Non-hematological toxicities were generally mild except for Grade 3 sensory neuropathy (n = 3). Pharmacokinetic study demonstrated the area under the curve of paclitaxel increased with increasing the dosage, and comparable pharmacokinetic parameters to the western population. Partial response was observed in three non-small cell lung cancer patients. Two of whom had received docetaxel-containing chemotherapy prior to the study. CONCLUSIONS: ABI-007 administered in every-3-week schedule was well tolerated up to 300 mg/m(2), and recommended dose was determined at 260 mg/m(2) in consideration of efficacy, toxicities and similarity of pharmacokinetic profile in western studies. Additional studies of single-agent ABI-007 as well as platinum-based combinations, particularly in patients with non-small cell lung cancer, are warranted.