PURPOSE: 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. PATIENTS & 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. CONCLUSION: 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.
PURPOSE: 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. PATIENTS & 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. CONCLUSION: 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: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: G Nasti; D Errante; R Talamini; G Rizzardini; M Fasan; G Landonio; C Zeroli; G Chichino; E Nigra; E Vaccher; U Tirelli Journal: J Clin Oncol Date: 2000-04 Impact factor: 44.544
Authors: Sean C Semple; Robert Leone; Jinfang Wang; Esther C Leng; Sandra K Klimuk; Merete L Eisenhardt; Zuan-Ning Yuan; Katarina Edwards; Norbert Maurer; Michael J Hope; Pieter R Cullis; Quet-Fah Ahkong Journal: J Pharm Sci Date: 2005-05 Impact factor: 3.534
Authors: Diederik F S Kehrer; Annelies M Bos; Jaap Verweij; Harry J Groen; Walter J Loos; Alex Sparreboom; Maja J A de Jonge; Marta Hamilton; Terri Cameron; Elisabeth G E de Vries Journal: J Clin Oncol Date: 2002-03-01 Impact factor: 44.544
Authors: E Bajetta; A Di Leo; L Biganzoli; L Mariani; F Cappuzzo; M Di Bartolomeo; N Zilembo; S Artale; E Magnani; L Celio; R Buzzoni; C Carnaghi Journal: J Clin Oncol Date: 1996-09 Impact factor: 44.544
Authors: Ryan F Schell; Brian J Sidone; Whitney P Caron; Mark D Walsh; Taylor F White; Beth A Zamboni; Ramesh K Ramanathan; William C Zamboni Journal: Nanomedicine Date: 2013-07-24 Impact factor: 5.307