Phase I trial of bortezomib daily dose: safety, pharmacokinetic profile, biological effects and early clinical evaluation in patients with advanced solid tumors

Investigational New Drugs
R BahledaJean-Charles Soria

Abstract

Purpose This phase I study investigated bortezomib in solid tumors used as a daily subcutaneous regimen. Previous regimens showed only modest activity in solid tumors which was potentially related to sub-optimal tumor penetration. We aimed at exploring if daily low dose administration of bortezomib may allow a greater and tolerable pharmacokinetic exposure which might be required for antitumor activity in solid tumors. Patients and methods This 3 + 3 design, dose escalation, monocentric study aimed at defining the maximum tolerated dose of daily low dose schedule of bortezomib. Tolerability, pharmacokinetics, pharmacodynamics, antitumor activity, biomarkers for proteasome inhibition, pre- and post-treatment tumor biopsies were also evaluated. Results A total of eighteen patients were dosed in 3 bortezomib cohorts (0.5, 0.6 and 0.7 mg/m2), with 3, 11 and 4 patients respectively. Three patients experienced dose-limiting toxicities: Grade (G) 3 Sweet's syndrome (at 0.6 mg/m2), G3 asthenia and anorexia or ataxia (2 patients at 0.7 mg/m2). The most common study drug-related adverse events (all grades) were thrombocytopenia (72%), fatigue (56%), neuropathy (50%), anorexia (44%) and rash (39%). Dose 0.6 mg/m2 of bortezomib was conside...Continue Reading

References

Jun 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christos N PapandreouChristopher J Logothetis
Dec 24, 2009·Cancer Research·Sebastian BauerAnette Duensing
Dec 18, 2013·Pharmacotherapy·Chrystia M ZobniwBernd G Barthel
Mar 19, 2015·Indian Journal of Dermatology, Venereology and Leprology·Mar Llamas-VelascoM Aragüés

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Citations

Sep 2, 2020·Scientific Reports·Angéla TakácsLászló Kőhidai
Aug 29, 2021·Pharmaceuticals·Angéla TakácsLászló Kőhidai

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