title: Phase I and pharmacokinetic study of polymeric  micelle‑formulated paclitaxel in adult Chinese patients  with advanced solid tumors.
abstract: OBJECTIVE
  Polymeric micelle-formulated paclitaxel (PM paclitaxel) is a nanoscale drug delivery compound. This study investigated the maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetic (PK) profile of PM paclitaxel in Chinese patients with treatment-refractory advanced or relapsed solid tumors.
  
  
  METHODS
  Dose escalation of PM paclitaxel followed the standard ‘3 + 3’ rule, starting at 175 mg/m(2). PM paclitaxel was administered over 3 h every 3 weeks. Patients were treated until disease progression, intolerance, death, or consent withdrawal. Blood samples were collected for PK testing.
  
  
  RESULTS
  A ll 23 patients were evaluable for toxicity. Neutropenia,neuropathy, and myalgia were the most common toxicities; acute hypersensitivity reaction was not observed. One of six patients at dose level 4 (350 mg/m(2)) and two of six patients at dose level 5 (390 mg/m(2)) developed grade 4 neutropenia. The MTD was 350 mg/m(2). No patients discontinued treatment because of neuropathy. Partial response was seen in five of 20 patients (25 %) who had response assessment, three of whom had prior exposure to taxanes (two were heavily pretreated). Ten patients (50 %)had stable disease at cycle 2 and only five patients (25 %) had disease progression. The area under the curve and the maximum concentration of paclitaxel increased with escalating doses, suggesting that PM paclitaxel has linear PKs.
  
  
  CONCLUSIONS
  The main dose-limiting toxicity for PM paclitaxel was neutropenia, and the recommended dose for phase II study is 300 mg/m(2). PM paclitaxel is superior to conventional paclitaxel for its simplified premedication regimen and delivery of a higher paclitaxel dose without increased neuropathy.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lv
authors.forename: Junning
authors.initials: J
authors.lastname: Cao
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: Si
authors.initials: S
authors.lastname: Sun
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Weijian
authors.initials: W
authors.lastname: Guo
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008823:Micelles; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D017239:Paclitaxel