ArticleInvestigational new drugs2018
Phase I study of the combination of crizotinib (as a MET inhibitor) and dasatinib (as a c-SRC inhibitor) in patients with advanced cancer.
Article in Investigational new drugs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evidence-Based Recommendations for Education Provided to Patients and Families Regarding the Adverse Events of ALK and MEK Inhibitors: A Systematic Review From the Children's Oncology Group.Journal of pediatric hematology/oncology nursingPooled it
- Phase II Study of Cabozantinib in Patients With Bone Metastasis.The oncologist · 2022Trial
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma.Cancers · 2022Review
- Targeted and systemic insights into the crosstalk between DNA-dependent protein kinase catalytic subunit and receptors of estrogen, progesterone and epidermal growth factor in the context of cancer.Molecular biology reports · 2022Review
- The hepatocyte growth factor/mesenchymal epithelial transition factor axis in high-risk pediatric solid tumors and the anti-tumor activity of targeted therapeutic agents.Frontiers in pediatrics · 2022Review
- SRC and PIM1 as potential co-targets to overcome resistance in MET deregulated non-small cell lung cancer.Translational lung cancer research · 2020Article
- MERTK in cancer therapy: Targeting the receptor tyrosine kinase in tumor cells and the immune system.Pharmacology & therapeutics · 2020Review
- Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned so Far.Cancers · 2020Review
- An Immune-Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood.Micromachines · 2020Article
- CXCL1-LCN2 paracrine axis promotes progression of prostate cancer via the Src activation and epithelial-mesenchymal transition.Cell communication and signaling : CCS · 2019Article
- Review
- Safety and Tolerability of c-MET Inhibitors in Cancer.Drug safety · 2019Review
- Targeting Upstream Kinases of STAT3 in Human Medulloblastoma Cells.Current cancer drug targets · 2019Article
- Targeting the HGF/MET Axis Counters Primary Resistance to KIT Inhibition inJCO precision oncology · 2018Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Background Both MET and c-SRC are important mediators of cancer progression and there is cross talk between the two molecules. Preclinical studies have demonstrated combination of MET and c-SRC inhibitors is effective in multiple cancer types. Methods We analyzed the safety and efficacy of administering a c-SRC inhibitor (dasatinib) in combination with a MET inhibitor (crizotinib) in a two-arm concurrent phase I study. Arm A consisted of crizotinib fixed at 250 mg twice per day with escalation of dasatinib. Arm B consisted of dasatinib fixed at 140 mg daily with escalation of crizotinib. Endpoints included dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), and response (RECIST 1.1). Results We enrolled 61 patients (arm A: 31, arm B: 30). The most common cancers were sarcoma (21%) and prostate cancer (16%). In Arm A, at dose level 2 (DL2), 40% (2/5) experienced DLTs. In the expanded DL1, 21% (4/19) experienced DLTs (all grade 3). In Arm B, at DL2, 50% (2/4) experienced DLTs. In the expanded DL1, 22% (4/18) experienced DLTs (all grade 3). RP2D was determined to be arm A, DL1 (250 mg crizotinib orally twice per day plus 50 mg dasatinib orally daily). Partial response (N = 1) and stable disease for ≥6 months (N = 3) were seen. Conclusions The combination of crizotinib and dasatinib is safe to administer but tolerability is limited given the high rate of adverse events. Responses and durable stable disease were limited. Further precision therapy approach using this specific combination may be difficult given the toxicity.
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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.