title: Phase I clinical trial of pegylated liposomal mitoxantrone plm60-s: pharmacokinetics, toxicity and preliminary efficacy.
abstract: OBJECTIVE
  Plm60-s is a pegylated liposomal mitoxantrone formulation, in which mitoxantrone was loaded into small unilamellar vesicles (~60 nm) made from solid lipid membrane. This two-arm, dose-escalating phase I study was designed to determine safety and pharmacokinetics of plm60-s, and to compare with those of conventional mitoxantrone injection (c-MI).
  
  
  METHODS
  Patients received an intravenous infusion of plm60-s at 6, 10, 12, 14, 16 and 18 mg/m(2) every 4 weeks. Three or 6 patients were in each group of dose level. If more than one third patients of a group experienced dose-limiting toxicity, dose climbing will stop. The control group of 3 patients received c-MI at 10 mg/m(2) every 28 days. Samples for pharmacokinetic studies were collected. The analysis of the safety and tolerability was done according to the record and laboratory examination, etc.
  
  
  RESULTS
  Twenty patients were enrolled. One grade 3 leukocytopenia occurred in plm60-s groups. Plm60-s was safer than c-MI at the same dose of 10 mg/m(2). Two complete responses and one partial response occurred in plm60-s group. In plasma, plm60-s exhibited sustained release of the content, resulting in the reduced peak concentrations and enhanced AUC of released MIT. Total mitoxantrone was linearly cleared, and mitoxantrone was predominantly in the liposomal encapsulation form. Repeated administration of plm60-s did not affect the clearance kinetics.
  
  
  CONCLUSIONS
  At a dose of up to 18 mg/m(2), plm60-s could be well tolerated and potential efficacy could be observed. The pharmacokinetic profile of plm60-s was remarkably altered. Further investigations are in progression.
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Yang
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
authors.forename: Chunlei
authors.initials: C
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Gui
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Han
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Song
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Du
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D008942:Mitoxantrone