ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Pharmacokinetics and safety of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction: phase I NCI Organ Dysfunction Working Group Study NCI-6432.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00091117 (A Phase I Pharmacokinetic Study of PS-341 in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEPSponsored Organ Dysfunction Working Group), which is not on this map. Cited by 40 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Pharmacokinetic Study of PS-341 in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEPSponsored Organ Dysfunction Working Group
Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- The use of novel agents in multiple myeloma patients with hepatic impairment.Future oncology (London, England) · 2015Pooled it
- Pharmacokinetics and pharmacodynamics of nab-paclitaxel in patients with solid tumors: disposition kinetics and pharmacology distinct from solvent-based paclitaxel.Journal of clinical pharmacology · 2014Pooled it
- Pharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment.British journal of clinical pharmacology · 2016Trial
- Pharmacokinetic, pharmacodynamic and covariate analysis of subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma.Clinical pharmacokinetics · 2012Trial
- Stratifying osteosarcoma patients using an epigenetic modification-related prognostic signature: implications for immunotherapy and chemotherapy selection.Translational cancer research · 2024Article
- Review
- Article
- Phase I and Pharmacokinetic Study of Romidepsin in Patients with Cancer and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- A Translational Physiologically Based Pharmacokinetics/Pharmacodynamics Framework of Target-Mediated Disposition, Target Inhibition and Drug-Drug Interactions of Bortezomib.The AAPS journal · 2020Article
- Clinical Pharmacokinetic and Pharmacodynamic Considerations in Treating Non-Hodgkin Lymphoma.Clinical pharmacokinetics · 2020Review
- Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Subjects with Hepatic Impairment.Clinical pharmacokinetics · 2019Article
- Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later.Drugs in R&D · 2019Review
- Pharmacodynamics and pharmacokinetics of proteasome inhibitors for the treatment of multiple myeloma.Expert opinion on drug metabolism & toxicology · 2019Review
- Consequences of Performing Parallel Dose Finding Trials in Heterogeneous Groups of Patients.JNCI cancer spectrum · 2019Article
- Clinical Pharmacokinetics and Pharmacodynamics of Bortezomib.Clinical pharmacokinetics · 2019Review
- Bortezomib therapy in a real-world setting in patients with relapsed or refractory multiple myeloma.Oncology reviews · 2019Article
- Pharmacokinetics and Exposure-Response Analyses of Daratumumab in Combination Therapy Regimens for Patients with Multiple Myeloma.Advances in therapy · 2018Article
- A Bayesian Adaptive Design in Cancer Phase I Trials using Dose Combinations in the Presence of a Baseline Covariate.Journal of probability and statistics · 2018Article
- Population pharmacokinetics of nintedanib, an inhibitor of tyrosine kinases, in patients with non-small cell lung cancer or idiopathic pulmonary fibrosis.Cancer chemotherapy and pharmacology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
purposeThe proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. EXPERIMENTAL
designPatients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m(2) standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m(2), respectively, up to a 1.3 mg/m(2) maximum. Serial blood samples were collected for 24 hours postdose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements.
resultsSixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC(0-tlast)) or C(max) compared with patients with normal function. Mean dose-normalized AUC(0-tlast) was increased by approximately 60% on day 8 in patients with moderate or severe impairment.
conclusionsPatients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m(2).
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.