ArticleBritish journal of clinical pharmacology2008
Population pharmacokinetic and pharmacodynamic analysis to support treatment optimization of combination chemotherapy with indisulam and carboplatin.
Article in British journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed.
- Population pharmacokinetic and pharmacodynamic analysis of linezolid and a hematologic side effect, thrombocytopenia, in Japanese patients.Antimicrobial agents and chemotherapy · 2011Trial
- Translational PK-PD/TD modeling of antitumor effects and peripheral neuropathy in gemcitabine and nab-paclitaxel chemotherapy from xenograft mice to patients for optimal dose and schedule.Cancer chemotherapy and pharmacology · 2024Article
- Indisulam Reduces Viability and Regulates Apoptotic Gene Expression in Pediatric High-Grade Glioma Cells.Biomedicines · 2022Article
- Relationship Between Antithymocyte Globulin Concentrations and Lymphocyte Sub-Populations in Kidney Transplant Patients.Clinical pharmacokinetics · 2022Article
- Impact of granulocyte colony-stimulating factor on FOLFIRINOX-induced neutropenia prevention: A population pharmacokinetic/pharmacodynamic approach.British journal of clinical pharmacology · 2020Article
- Predicting Chemotherapy-Induced Neutropenia and Granulocyte Colony-Stimulating Factor Response Using Model-Based In Vitro to Clinical Translation.The AAPS journal · 2020Article
- Proteolysis-targeting chimeras in drug development: A safety perspective.British journal of pharmacology · 2020Review
- Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic-pharmacodynamic model in gastrointestinal cancer patients.Cancer chemotherapy and pharmacology · 2020Article
- Quantifying Drug-Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model.CPT: pharmacometrics & systems pharmacology · 2019Article
- Population Pharmacokinetic-Pharmacodynamic Modeling of 5-Fluorouracil for Toxicities in Rats.European journal of drug metabolism and pharmacokinetics · 2017Article
- Application of hematological toxicity modeling in clinical development of abexinostat (S-78454, PCI-24781), a new histone deacetylase inhibitor.Pharmaceutical research · 2013Article
- A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model.Investigational new drugs · 2012Article
- Predictive ability of a semi-mechanistic model for neutropenia in the development of novel anti-cancer agents: two case studies.Investigational new drugs · 2011Article
- The pharmacokinetic/pharmacodynamic pipeline: translating anticancer drug pharmacology to the clinic.The AAPS journal · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsIndisulam and carboplatin have shown synergistic activity in preclinical studies. In a dose escalation study of the combination, a treatment delay was frequently required in a 3-weekly regimen to allow recovery from myelosuppression from previous cycles. A 4-weekly regimen was better tolerated, but had a decreased dose-intensity which may compromise efficacy. The aims of this study were (i) to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to describe the myelosuppressive effect of the combination, and (ii) to use this model to select a dosing regimen for Phase II evaluation.
methodsSixteen patients were treated at four different dose levels of indisulam (1-h infusion on day 1) and carboplatin (30-min infusion on day 2). Pharmacokinetic data were analysed with nonlinear mixed effects modelling. A semiphysiological model describing chemotherapy-induced myelosuppression characterized the relationship between the pharmacokinetics and the haematological toxicity of indisulam and carboplatin. A simulation study was performed to evaluate the tolerability and dose-intensity for 3-weekly and 4-weekly treatment regimens.
resultsThe PK-PD model described the pharmacokinetics and the myelosuppressive effect of indisulam and carboplatin. The risk of a treatment delay at cycle 2 due to myelosuppression was unacceptably high (34-65%) in a 3-weekly regimen for various dose levels (350-600 mg m(-2) indisulam in combination with carboplatin to achieve an AUC of 4-6 mg min(-1) ml(-1)). This risk was acceptable for a 4-weekly regimen (9-24%), which is in line with the clinical study results.
conclusionsThis PK-PD study supports the selection of indisulam 500 mg m(-2) and a dose of carboplatin to achieve an AUC of 6 mg min(-1) ml(-1) in a 4-weekly regimen as the recommended dose for future studies.
Indexed as
Identifiers
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.