ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2011
Phase I trial of lenalidomide and CCI-779 in patients with relapsed multiple myeloma: evidence for lenalidomide-CCI-779 interaction via P-glycoprotein.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 85 citations in OpenAlex.
- Pharmacogenetic study of the impact of ABCB1 single-nucleotide polymorphisms on lenalidomide treatment outcomes in patients with multiple myeloma: results from a phase IV observational study and subsequent phase II clinical trial.Cancer chemotherapy and pharmacology · 2018Trial
- A Phase I/II Trial of Panobinostat in Combination With Lenalidomide in Patients With Relapsed or Refractory Hodgkin Lymphoma.Clinical lymphoma, myeloma & leukemia · 2017Trial
- No clinically significant drug interactions between lenalidomide and P‑glycoprotein substrates and inhibitors: results from controlled phase I studies in healthy volunteers.Cancer chemotherapy and pharmacology · 2014Trial
- Chemosensory role of intracellular TAS2Rs, the activation of which triggers drug excretion by ABCB1 in cancer cells.Scientific reports · 2025Article
- Push Forward Clinical Management of Hematological Toxicity due to Lenalidomide Overexposure: Model-Informed Precision Dosing for Chinese Population With Renal Insufficiency.CPT: pharmacometrics & systems pharmacology · 2025Article
- Targeting neuroinflammation: 3-monothiopomalidomide a new drug candidate to mitigate traumatic brain injury and neurodegeneration.Journal of biomedical science · 2025Article
- ABCG2 Mediates Resistance to the Dual EGFR and PI3K Inhibitor MTX-211 in Cancer Cells.International journal of molecular sciences · 2024Article
- Imperatorin Restores Chemosensitivity of Multidrug-Resistant Cancer Cells by Antagonizing ABCG2-Mediated Drug Transport.Pharmaceuticals (Basel, Switzerland) · 2023Article
- A New Generation of IMiDs as Treatments for Neuroinflammatory and Neurodegenerative Disorders.Biomolecules · 2023Review
- Article
- A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma.Scientific reports · 2021Observational
- Drug and Solute Transporters in Mediating Resistance to Novel Therapeutics in Multiple Myeloma.ACS pharmacology & translational science · 2021Review
- Overexpression of ABCB1 and ABCG2 contributes to reduced efficacy of the PI3K/mTOR inhibitor samotolisib (LY3023414) in cancer cell lines.Biochemical pharmacology · 2020Article
- Licochalcone A Selectively Resensitizes ABCG2-Overexpressing Multidrug-Resistant Cancer Cells to Chemotherapeutic Drugs.Journal of natural products · 2020Article
- The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside.Frontiers in oncology · 2020Review
- The Selective Class IIa Histone Deacetylase Inhibitor TMP195 Resensitizes ABCB1- and ABCG2-Overexpressing Multidrug-Resistant Cancer Cells to Cytotoxic Anticancer Drugs.International journal of molecular sciences · 2019Article
- Development of a physiologically based pharmacokinetic model for intravenous lenalidomide in mice.Cancer chemotherapy and pharmacology · 2019Article
- Avapritinib: A Selective Inhibitor of KIT and PDGFRα that Reverses ABCB1 and ABCG2-Mediated Multidrug Resistance in Cancer Cell Lines.Molecular pharmaceutics · 2019Article
- Influence of ABCB1 polymorphisms on the pharmacokinetics and toxicity of lenalidomide in patients with multiple myeloma.Medical oncology (Northwood, London, England) · 2019Article
- Population pharmacokinetics of lenalidomide in patients with B-cell malignancies.British journal of clinical pharmacology · 2019Article
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21 authors at 1 institution in 1 country.
Funding
Abstract
purposeMultiple myeloma (MM) is an incurable plasma-cell neoplasm for which most treatments involve a therapeutic agent combined with dexamethasone. The preclinical combination of lenalidomide with the mTOR inhibitor CCI-779 has displayed synergy in vitro and represents a novel combination in MM. PATIENTS AND
methodsA phase I clinical trial was initiated for patients with relapsed myeloma with administration of oral lenalidomide on days 1 to 21 and CCI-779 intravenously once per week during a 28-day cycle. Pharmacokinetic data for both agents were obtained, and in vitro transport and uptake studies were conducted to evaluate potential drug-drug interactions.
resultsTwenty-one patients were treated with 15 to 25 mg lenalidomide and 15 to 20 mg CCI-779. The maximum-tolerated dose (MTD) was determined to be 25 mg lenalidomide with 15 mg CCI-779. Pharmacokinetic analysis indicated increased doses of CCI-779 resulted in statistically significant changes in clearance, maximum concentrations, and areas under the concentration-time curves, with constant doses of lenalidomide. Similar and significant changes for CCI-779 pharmacokinetics were also observed with increased lenalidomide doses. Detailed mechanistic interrogation of this pharmacokinetic interaction demonstrated that lenalidomide was an ABCB1 (P-glycoprotein [P-gp]) substrate.
conclusionThe MTD of this combination regimen was 25 mg lenalidomide with 15 mg CCI-779, with toxicities of fatigue, neutropenia, and electrolyte wasting. Pharmacokinetic and clinical interactions between lenalidomide and CCI-779 seemed to occur, with in vitro data indicating lenalidomide was an ABCB1 (P-gp) substrate. To our knowledge, this is the first report of a clinically significant P-gp-based drug-drug interaction with lenalidomide.
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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.