title: A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor.
abstract: OBJECTIVE
  This phase I study was performed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of an untargeted liposomal formulation of vinorelbine (NanoVNB®) and to characterize its plasma pharmacokinetics in patients with advanced solid tumors which were refractory to conventional treatment or without an effective treatment.
  
  
  METHODS
  The study incorporated an accelerated titration design. Twenty-two patients with various solid tumors were enrolled. NanoVNB(®) was administered intravenously at doses of 2.2-23 mg/m(2) once every 14 days. Pharmacokinetic endpoints were evaluated in the first cycle. The safety profiles and anti-tumor effects of NanoVNB® were also determined.
  
  
  RESULTS
  Skin rash was the DLT and the most common non-hematological toxicity. The MTD was 18.5 mg/m(2). Drug-related grade 3-4 hematological toxicities were infrequent. Compared with intravenous free vinorelbine, NanoVNB® showed a high C(max) and low plasma clearance. Of the 11 patients completing at least 1 post-treatment tumor assessment, 5 had stable disease. No responders were noted.
  
  
  CONCLUSIONS
  NanoVNB® was well tolerated and exhibited more favorable pharmacokinetic profiles than free vinorelbine. Based on dose-limiting skin toxicity, further evaluation of NanoVNB® starting from 18.5 mg/m(2) as a single agent or in combination with other chemotherapeutic agents for vinorelbine-active malignancies is warranted.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei 10016, Taiwan.
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Yang
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Zhong-Zhe
authors.initials: ZZ
authors.lastname: Lin
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Tseng
authors.forename: Ruey-Long
authors.initials: RL
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D020714:Maximum Tolerated Dose; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013624:Taiwan; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014747:Vinblastine; D000077235:Vinorelbine
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