title: Phase I and pharmacokinetic study of nab-paclitaxel, nanoparticle albumin-bound paclitaxel, administered weekly to Japanese patients with solid tumors and metastatic breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. mandoh@ncc.go.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Ando
authors.forename: Kan
authors.initials: K
authors.lastname: Yonemori
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimizu
authors.forename: Taizo
authors.initials: T
authors.lastname: Hirata
authors.forename: Harukaze
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Mayu
authors.initials: M
authors.lastname: Yunokawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy / Q000208:ethnology / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism*; D017239:Paclitaxel / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel