Trial reportCancer chemotherapy and pharmacology2015
Pharmacokinetic and pharmacodynamic study of tariquidar (XR9576), a P-glycoprotein inhibitor, in combination with doxorubicin, vinorelbine, or docetaxel in children and adolescents with refractory solid tumors.
Trial report in Cancer chemotherapy and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 68 citations in OpenAlex.
- Impact of pharmacogenetics on variability in exposure to oral vinorelbine among pediatric patients: a model-based population pharmacokinetic analysis.Cancer chemotherapy and pharmacology · 2022Trial
- P-glycoprotein-mediated efflux of rapaprotin-L dictates sensitivity of cancer cells to the inducer of 26S proteasome disassembly.European journal of pharmacology · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- Enhanced plasma and brain concentrations and medulloblastoma cytotoxicity of asciminib and nilotinib by P-glycoprotein inhibition with tariquidar.Anti-cancer drugs · 2025Article
- Overcoming resistance in advanced urothelial carcinoma: mechanisms of escape from antibody-drug conjugates and FGFR3 inhibition.Frontiers in oncology · 2025Review
- Review
- A ciprofloxacin derivative with four mechanisms of action overcomes paclitaxel resistance in p53-mutant and MDR1 gene-expressing type II human endometrial cancer.Biomaterials · 2023Article
- Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.Cancers · 2023Review
- Comprehensive Evaluation of Multiple Approaches Targeting ABCB1 to Resensitize Docetaxel-Resistant Prostate Cancer Cell Lines.International journal of molecular sciences · 2022Article
- Early Mechanisms of Chemoresistance in Retinoblastoma.Cancers · 2022Article
- Infigratinib (BGJ 398), a Pan-FGFR Inhibitor, Targets P-Glycoprotein and Increases Chemotherapeutic-Induced Mortality of Multidrug-Resistant Tumor Cells.Biomedicines · 2022Article
- Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy.Theranostics · 2022Review
- Article
- Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapyActa pharmaceutica Sinica. B · 2021Article
- The Long-Term DEHP Exposure Confers Multidrug Resistance of Triple-Negative Breast Cancer Cells through ABC Transporters and Intracellular ROS.Antioxidants (Basel, Switzerland) · 2021Article
- A novel pharmacotherapy approach using P-glycoprotein (PGP/ABCB1) efflux inhibitor combined with ivermectin to reduce alcohol drinking and preference in mice.Alcohol (Fayetteville, N.Y.) · 2020Article
- Overcoming Multidrug Resistance: Flavonoid and Terpenoid Nitrogen-Containing Derivatives as ABC Transporter Modulators.Molecules (Basel, Switzerland) · 2020Review
- Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cellsActa pharmaceutica Sinica. B · 2020Article
- ABC Transporter Inhibition Plus Dexamethasone Enhances the Efficacy of Convection Enhanced Delivery in H3.3K27M Mutant Diffuse Intrinsic Pontine Glioma.Neurosurgery · 2020Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
purposeP-glycoprotein (Pgp), an ATP-dependent transport protein, confers multidrug resistance in cancer cells. Tariquidar binds and inhibits Pgp. To assess the toxicity, pharmacokinetics (PK), and pharmacodynamics of tariquidar, we conducted a phase I trial of tariquidar in combination with doxorubicin, docetaxel, or vinorelbine in children and adolescents with recurrent or refractory solid tumors.
methodsPatients less than 19 years of age with refractory or recurrent solid tumors were eligible. Tariquidar (1, 1.5, or 2 mg/kg) was administered alone and in combination with doxorubicin, docetaxel, or vinorelbine. PK of tariquidar and cytotoxic drugs was performed. Pgp function was assessed by a rhodamine efflux assay and (99m)Tc-sestamibi scintigraphy. Tumor Pgp expression was assessed by immunohistochemistry. Response was assessed using Response Evaluation Criteria in Solid Tumors.
resultsTwenty-nine subjects were enrolled. No tariquidar-related dose-limiting toxicity (DLT) was observed. DLT related to cytotoxic drugs occurred in 12 % of subjects receiving tariquidar 2 mg/kg. When administered in combination with tariquidar, the clearance of docetaxel and vinorelbine was reduced compared to prior studies. Inhibition of rhodamine efflux was dose dependent. After tariquidar administration, (99m)Tc-sestamibi accumulation in tumor increased by 22 %. Objective responses (1 complete, 2 partial) were observed. There was no association between tumor Pgp expression and response.
conclusionA tolerable and biologically active dose of tariquidar was established in children and adolescents. This trial demonstrates that modulators of resistance can be evaluated in combination with chemotherapy, and pharmacokinetic and pharmacodynamic endpoints can be useful in determination of recommended dose in children and adolescents.
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.