Phase I and pharmacokinetic study of nab-paclitaxel, nanoparticle albumin-bound paclitaxel, administered weekly to Japanese patients with solid tumors and metastatic breast cancer

We conducted phase I and tolerability studies to determine the maximum tolerated dose (MTD) and recommended dose of nab-paclitaxel when administered weekly with solid tumors and to evaluate the tolerability of weekly administration at a dose of 150 mg/m(2) with metastatic breast cancer (MBC) as a first-line therapy in Japanese patients. In this phase I study, patients with advanced solid tumors received nab-paclitaxel at dose levels of 80-125 mg/m(2) as 30-min infusions once a week for three weekly doses repeated every 4 weeks. In the tolerability study, patients received 150 mg/m(2) nab-paclitaxel. Blood samples at the first dose of nab-paclitaxel were collected for pharmacokinetic analysis. Fifteen patients were treated for a median of five cycles in the phase I study. The MTD was 125 mg/m(2); the dose-limiting toxicity was neutropenia requiring skipping of the second or third weekly administration in the first cycle. In the tolerability study, six patients were treated for a median of six cycles; no intolerable toxicities were observed in the first cycle. Grade 3 sensory and motor neuropathy was observed in four and one patients, respectively. Ocular toxicities were observed in two patients (keratopathy and macular hole). Maximum paclitaxel concentration and area under the curve increased linearly with the dose. Weekly administration of nab-paclitaxel was well tolerated up to 100 mg/m(2) by heavily pretreated patients. For MBC patients, 150 mg/m(2) nab-paclitaxel as a first-line therapy was well tolerated. Dose reduction due to neuropathy allows multiple cycles of treatment.