A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor.
Summary of "A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor."
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(R)) 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((R)) 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(R) 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(R) 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(R) was well tolerated and exhibited more favorable pharmacokinetic profiles than free vinorelbine. Based on dose-limiting skin toxicity, further evaluation of NanoVNB(R) starting from 18.5 mg/m(2) as a single agent or in combination with other chemotherapeutic agents for vinorelbine-active malignancies is warranted.
Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei, 10016, Taiwan.
This article was published in the following journal.
Name: Investigational new drugs
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20809205
- DOI: http://dx.doi.org/10.1007/s10637-010-9522-3
Medical and Biotech [MESH] Definitions
Leukemia, Myelogenous, Chronic, Bcr-abl Positive
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Clinical Trial, Phase Iii
Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques after phase II trials. A large enough group of patients is studied and closely monitored by physicians for adverse response to long-term exposure, over a period of about three years in either the United States or a foreign country.
Clinical Trials, Phase Iii As Topic
Comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries.
Leukemia, Myeloid, Chronic-phase
The initial phase of chronic myeloid leukemia consisting of an relatively indolent period lasting from 4 to 7 years. Patients range from asymptomatic to those exhibiting ANEMIA; SPLENOMEGALY; and increased cell turnover. There are 5% or fewer blast cells in the blood and bone marrow in this phase.
Clinical Trial, Phase Ii
Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques based on several hundred volunteers, including a limited number of patients, and conducted over a period of about two years in either the United States or a foreign country.
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