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Phase I and pharmacokinetic study of nab-paclitaxel, nanoparticle albumin-bound paclitaxel, administered weekly to Japanese patients with solid tumors and metastatic breast cancer.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2012 Feb; Vol. 69 (2), pp. 457-65. Date of Electronic Publication: 2011 Aug 19. - Publication Year :
- 2012
-
Abstract
- Purpose: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions: 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.
- Subjects :
- Adult
Aged
Albumin-Bound Paclitaxel
Albumins adverse effects
Albumins pharmacokinetics
Albumins therapeutic use
Antineoplastic Agents, Phytogenic adverse effects
Antineoplastic Agents, Phytogenic pharmacokinetics
Antineoplastic Agents, Phytogenic therapeutic use
Area Under Curve
Asian People
Breast Neoplasms drug therapy
Breast Neoplasms ethnology
Breast Neoplasms metabolism
Diarrhea chemically induced
Dose-Response Relationship, Drug
Drug Administration Schedule
Exanthema chemically induced
Female
Humans
Japan
Male
Metabolic Clearance Rate
Middle Aged
Nanoparticles administration & dosage
Nanoparticles adverse effects
Nanoparticles therapeutic use
Nausea chemically induced
Neoplasm Metastasis
Neoplasms ethnology
Paclitaxel adverse effects
Treatment Outcome
Neoplasms drug therapy
Neoplasms metabolism
Paclitaxel pharmacokinetics
Paclitaxel therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0843
- Volume :
- 69
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21853310
- Full Text :
- https://doi.org/10.1007/s00280-011-1726-5