ArticleBMC cancer2015
NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases.Future oncology (London, England) · 2019Trial
- Randomized study of etirinotecan pegol versus irinotecan as second-line treatment for metastatic colorectal cancer.Cancer chemotherapy and pharmacology · 2017Trial
- The research progress on meningeal metastasis in solid tumors.Discover oncology · 2025Review
- PLX038A, a long-acting SN-38, penetrates the blood-tumor-brain-barrier, accumulates and releases SN-38 in brain tumors to increase survival of tumor bearing mice.Scientific reports · 2024Article
- The Effect of PEGylation on Drugs' Pharmacokinetic Parameters; from Absorption to Excretion.Current drug delivery · 2024Review
- Systemic treatments for breast cancer brain metastasis.Frontiers in oncology · 2022Review
- Blood-Brain Barrier in Brain Tumors: Biology and Clinical Relevance.International journal of molecular sciences · 2021Review
- Modulation of the blood-tumor barrier to enhance drug delivery and efficacy for brain metastases.Neuro-oncology advances · 2021Article
- A Very Long-Acting PARP Inhibitor Suppresses Cancer Cell Growth in DNA Repair-Deficient Tumor Models.Cancer research · 2021Article
- Nanoparticles Containing a Combination of a Drug and an Antibody for the Treatment of Breast Cancer Brain Metastases.Molecular pharmaceutics · 2020Article
- Characterization of Oncolytic Vaccinia Virus Harboring the Human IFNB1 and CES2 Transgenes.Cancer research and treatment · 2020Article
- Current state of clinical trials in breast cancer brain metastases.Neuro-oncology practice · 2019Article
- Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer.BMC cancer · 2018Article
- Bevacizumab, irinotecan, temozolomide, tyrosine kinase inhibition, and MEK inhibition are effective against pleomorphic xanthoastrocytoma regardless of V600E status.Journal of neuro-oncology · 2018Article
- Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases.Pharmacological research · 2018Review
- Liposomal Irinotecan Accumulates in Metastatic Lesions, Crosses the Blood-Tumor Barrier (BTB), and Prolongs Survival in an Experimental Model of Brain Metastases of Triple Negative Breast Cancer.Pharmaceutical research · 2018Article
- Translational gap in ongoing clinical trials for glioma.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2018Review
- Therapy of breast cancer brain metastases: challenges, emerging treatments and perspectives.Therapeutic advances in medical oncology · 2018Review
- Article
- Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.Breast cancer research and treatment · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundBrain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity.
methodsFemale nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively).
resultsNKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (>20 ng/g for 168 h) versus conventional irinotecan (>1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals.
conclusionsElevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m(2) NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results.
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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.