A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor.
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.
Yang
Shih-Hung
SH
Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei 10016, Taiwan.
Lin
Chia-Chi
CC
Lin
Zhong-Zhe
ZZ
Tseng
Yun-Long
YL
Hong
Ruey-Long
RL
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
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014747:Vinblastine; D000077235:Vinorelbine
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