ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
A phase I study of a 2-day lapatinib chemosensitization pulse preceding nanoparticle albumin-bound Paclitaxel for advanced solid malignancies.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00313599 (A Phase I Dose Escalation Study of a 2 Day Oral Lapatinib Chemosensitization Pulse Given Prior To Weekly Intravenous Abraxane™ in Patients With Advanced Solid Tumors), which is not on this map. Cited by 20 papers.
What it found
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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.
A Phase I Dose Escalation Study of a 2 Day Oral Lapatinib Chemosensitization Pulse Given Prior To Weekly Intravenous Abraxane™ in Patients With Advanced Solid Tumors
Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- Effect of lapatinib on meningioma growth in adults with neurofibromatosis type 2.Journal of neuro-oncology · 2018Trial
- Report of safety of pulse dosing of lapatinib with temozolomide and radiation therapy for newly-diagnosed glioblastoma in a pilot phase II study.Journal of neuro-oncology · 2017Trial
- Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma.Neuro-oncology · 2015Trial
- Article
- Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer.PloS one · 2021Article
- Nanoparticles as immunomodulators and translational agents in brain tumors.Journal of neuro-oncology · 2021Review
- Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Mathematical modeling identifies optimum lapatinib dosing schedules for the treatment of glioblastoma patients.PLoS computational biology · 2018Article
- Imaging and therapy of ovarian cancer: clinical application of nanoparticles and future perspectives.Theranostics · 2018Review
- Bionanotechnology and the future of glioma.Surgical neurology international · 2015Article
- Overcoming the stromal barrier: technologies to optimize drug delivery in pancreatic cancer.Therapeutic advances in medical oncology · 2012Article
- Engineering solid lipid nanoparticles for improved drug delivery: promises and challenges of translational research.Drug delivery and translational research · 2012Article
- Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors.Cancer discovery · 2012Article
- "Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer.Neuro-oncology · 2011Article
- Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model.Nanotoxicology · 2011Article
- Off-target lapatinib activity sensitizes colon cancer cells through TRAIL death receptor up-regulation.Science translational medicine · 2011Article
- Reduced dose and intermittent treatment with lapatinib and trastuzumab for potent blockade of the HER pathway in HER2/neu-overexpressing breast tumor xenografts.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Article
- Molecular targeted approaches for treatment of pancreatic cancer.Current pharmaceutical design · 2011Review
- Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer.Breast cancer : basic and clinical research · 2011Article
- Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.Particle and fibre toxicology · 2010Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
purposeSystemic chemotherapy fails to access much of the tumor burden in patients with advanced cancer, significantly limiting its efficacy. In preclinical studies, brief high doses of tyrosine kinase inhibitors (TKI) targeting the human epidermal growth factor receptor (HER) family can prime tumor vasculature for optimal chemotherapeutic delivery and efficacy. This study investigates the clinical relevance of this approach. EXPERIMENTAL
designA phase I clinical study of escalating doses of the HER TKI lapatinib given as a 2-day pulse before a weekly infusion of nab-paclitaxel (100 mg/m(2)) was conducted in patients with advanced solid tumors.
resultsTwenty-five patients were treated. Treatment was associated with grade 1 to 2 toxicities including diarrhea, nausea, rash, neutropenia, neuropathy, fatigue, alopecia, and anemia. The two dose-limiting toxicities were grade 3 vomiting and grade 4 neutropenia, and the maximum tolerated dose of lapatinib was defined as 5250 mg/day in divided doses. Lapatinib concentrations increased with increasing dose. Dynamic Contrast Enhanced Magnetic Resonance Imaging studies in a subset of patients confirmed a decrease in tumor vascular permeability immediately following a lapatinib pulse. Sixty-five percent of evaluable patients experienced a partial or stable response on this therapy, 72% of whom were previously taxane-refractory.
conclusionA 2-day pulse of high-dose lapatinib given before weekly nab-paclitaxel is a feasible and tolerable clinical regimen, suitable for testing this novel vascular-priming chemosensitization hypothesis developed in preclinical models.
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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.