ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases.Breast (Edinburgh, Scotland) · 2023Pooled it
- Pertuzumab Plus High-Dose Trastuzumab in Patients With Progressive Brain Metastases and HER2-Positive Metastatic Breast Cancer: Primary Analysis of a Phase II Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Preclinical evaluation of trastuzumab deruxtecan in a new HER2+ leptomeningeal colonization model.Cancer letters · 2026Article
- Article
- Mathematical Oncology: How Modeling Is Transforming Clinical Decision-Making.Cancer research · 2025Review
- Managing hydrocephalus in patients with leptomeningeal disease: A multicenter retrospective analysis.International journal of cancer · 2025Article
- Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.Neuro-oncology · 2024Review
- Applications of cerebrospinal fluid circulating tumor cells and circulating tumor-derived DNA in diagnosis, prognosis, and personalized treatment of CNS metastases.Frontiers in oncology · 2024Review
- Narrative Review of Multidisciplinary Management of Central Nervous Involvement in Patients with HER2-Positive Metastatic Breast Cancer: Focus on Elderly Patients.Advances in therapy · 2023Review
- Article
- Review
- EGFR is a potential dual molecular target for cancer and Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Major hurdles to the use of tyrosine kinase inhibitors in clinical prevention/interception studies: Do preclinical studies with EGFR inhibitors suggest approaches to overcome some of the limitations.Frontiers in cell and developmental biology · 2023Review
- Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis.Breast care (Basel, Switzerland) · 2022Review
- Leptomeningeal Metastases: New Opportunities in the Modern Era.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Leptomeningeal metastasis fromTranslational cancer research · 2022Article
- Advances in the Diagnosis and Treatment of Leptomeningeal Disease.Current neurology and neuroscience reports · 2022Review
- Optimizing the future: how mathematical models inform treatment schedules for cancer.Trends in cancer · 2022Review
- Optimal Strategy and Benefit of Pulsed Therapy Depend On Tumor Heterogeneity and Aggressiveness at Time of Treatment Initiation.Molecular cancer therapeutics · 2022Article
- Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeLapatinib and capecitabine cross the blood-tumor barrier in breast cancer brain metastasis but have modest clinical efficacy. Administration of high-dose tyrosine kinase inhibitor has been evaluated in brain metastases and primary brain tumors as a strategy to improve drug exposure in the central nervous system (CNS). We derived a rational drug scheduling of intermittent high-dose lapatinib alternating with capecitabine based on our preclinical data and Norton-Simon mathematical modeling. We tested this intermittent, sequential drug schedule in patients with breast cancer with CNS metastasis. PATIENTS AND
methodsWe conducted a phase I trial using an accelerated dose escalation design in patients with HER2-positive (HER2
resultsEleven patients were enrolled: brain only (4 patients, 36%), leptomeningeal (5 patients, 45%), and intramedullary spinal cord (2 patients, 18%). Grade 3 nausea and vomiting were dose-limiting toxicities. The MTD of lapatinib was 1,500 mg BID. Three patients remained on therapy for greater than 6 months.
conclusionsHigh-dose lapatinib is tolerable when given intermittently and sequentially with capecitabine. Antitumor activity was noted in both CNS and non-CNS sites of disease. This novel administration regimen is feasible and efficacious in patients with HER2
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