Document Detail


A phase I study of liposomal-encapsulated docetaxel (LE-DT) in patients with advanced solid tumor malignancies.
MedLine Citation:
PMID:  23274395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Docetaxel is a taxane anticancer drug used in a wide variety of solid tumors. Liposomes are versatile drug carriers that may increase drug solubility, serve as sustained release systems, provide protection from drug degradation and toxicities, and help overcome multidrug resistance. This phase I study was conducted to determine the maximum tolerated dose, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and clinical response of liposomal-encapsulated docetaxel (LE-DT) in patients with advanced solid tumor malignancies.
METHODS: LE-DT was administered using a standard 3 + 3 dose escalation schema with dose levels of 50, 65, 85, 110, and 132 mg/m(2) IV on a 3-week cycle. Toxicities were assessed using the NCI-CTCAE version 3.0, and response was assessed using RECIST criteria (version 1.0). PK samples were drawn during cycle 1 and analyzed using a non-compartmental analysis.
RESULTS: Twenty-four patients were treated for 1-30 cycles (median = 4). No DLTs were experienced through dose levels of 50, 65, 85, and 110 mg/m(2). Two out of two patients experienced grade 4 neutropenia at the 132 mg/m(2) dose level. When an additional three patients were treated at the expanded 110 mg/m(2) dose level, two experienced grade 4 neutropenia. The 85 mg/m(2) dose level was reassessed with an expanded group of three additional patients, and only one of three patients experienced grade 4 neutropenia. The protocol was amended to allow G-CSF during cycle 1, and an additional three patients were treated at 110 mg/m(2) with no DLTs experienced. No patient experienced significant neuropathy, even patients treated for 19, 20, and 30 cycles. PK followed a two-compartment elimination pattern; there was no correlation between PK and toxicity. Two patients with thyroid and neuroendocrine cancer had partial responses (PR, 8%), and one patient with non-small-cell lung cancer had an unconfirmed PR. Eight patients (33%) had stable disease lasting more than 3 months, for a clinical benefit rate of 41%.
CONCLUSION: LE-DT was well tolerated with expected toxicities of neutropenia, anemia, and fatigue, but without neuropathy or edema. Clinical benefit (SD + PR) was observed in 41% of the patients. The recommended phase II dose of LE-DT is 85 mg/m(2) without G-CSF or 110 mg/m(2) with G-CSF.
Authors:
John F Deeken; Rebecca Slack; Glen J Weiss; Ramesh K Ramanathan; Michael J Pishvaian; Jimmy Hwang; Karen Lewandowski; Deepa Subramaniam; Aiwu Ruth He; Ion Cotarla; Aquilur Rahman; John L Marshall
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article     Date:  2012-12-30
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  71     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-25     Completed Date:  2013-04-08     Revised Date:  2014-04-18    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  627-33     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT01151384
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antineoplastic Agents, Phytogenic / administration & dosage*,  therapeutic use*
Area Under Curve
Cohort Studies
Drug Administration Schedule
Drug Carriers
Drug Compounding
Drug Resistance, Neoplasm
Excipients
Female
Freeze Drying
Half-Life
Humans
Infusions, Intravenous
Liposomes
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms / drug therapy*
Taxoids / administration & dosage*,  therapeutic use*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
P30 CA016672/CA/NCI NIH HHS; P30 CA051008/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Drug Carriers; 0/Excipients; 0/Liposomes; 0/Taxoids; 15H5577CQD/docetaxel
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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