Abstract | BACKGROUND: METHODS: Patients received OM-174 twice weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 μg/m(2). Blood samples for pharmacokinetic analysis and cytokine dosages were collected. NK cells activity and Toll-like receptors 4 polymorphism analysis were also performed. RESULTS: Seventeen patients were included. The highest dose administered was 1000 μg/m(2) repeated in 15 injections. The most common toxicities were a chills, fever, nausea/ vomiting, diarrhea, fatigue and headache. No patient experienced haematological side effects. As no dose limiting toxicity was observed, despite a grade 3 respiratory complication, the maximal tolerated dose and recommended dose were not established. Three patients exhibited disease stabilization with a mean duration of 4 months. Pharmacokinetic profile of OM-174 was characterized by a low distribution volume and clearance. Analysis of TLR 4 polymorphysm showed that most (16/17) patients carried the wild type alleles. A progressive increase in NK cell number and activity was observed only in patients receiving 1000 μg/m(2) of OM-174. A peak of IL-8 and IL-10 concentrations were observed after each OM-174 injection. Peaks of TNF-alpha and IL-6 concentrations were detected after the first infusion and decreased progressively suggesting tolerance. CONCLUSION: OM-174 therapy was well tolerated at biologically active concentrations. Whereas the recommended dose was not determined, further studies are planned in combination with chemotherapy as animal models suggest a strong synergistic antitumor effect. TRIAL REGISTRATION: NCT01800812 (ClinicalTrials.gov Identifier).
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Authors | Nicolas Isambert, Pierre Fumoleau, Catherine Paul, Christophe Ferrand, Sylvie Zanetta, Jacques Bauer, Kevin Ragot, Gérard Lizard, Jean-François Jeannin, Marc Bardou |
Journal | BMC cancer
(BMC Cancer)
Vol. 13
Pg. 172
(Apr 02 2013)
ISSN: 1471-2407 [Electronic] England |
PMID | 23547558
(Publication Type: Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Antineoplastic Agents
- Cytokines
- Lipopolysaccharides
- Toll-Like Receptor 4
- defoslimod
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Topics |
- Adult
- Aged
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacology, therapeutic use)
- Cell Line, Tumor
- Cytokines
(blood)
- Disease Models, Animal
- Drug Administration Schedule
- Female
- Humans
- Killer Cells, Natural
(drug effects, immunology)
- Lipopolysaccharides
(administration & dosage, pharmacology, therapeutic use)
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasms
(drug therapy, genetics, immunology)
- Polymorphism, Genetic
- Rats
- Toll-Like Receptor 4
(genetics)
- Treatment Outcome
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