ArticleBritish journal of cancer2012
Phase I clinical trial of the Src inhibitor dasatinib with dacarbazine in metastatic melanoma.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review.Journal of the American Heart Association · 2017Pooled it
- Trial
- BCL2-Associated Transcription Factor 1 Promotes SRC/Hypoxia-Inducible Factor 1 Subunit α-Mediated Cancer Stemness in Radioresistant Triple-Negative Breast Cancer.Oncology research · 2026Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- The Contribution of Nanomedicine in Ocular Oncology.Cancers · 2025Review
- Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.Cancers · 2022Review
- Unbiased High-Throughput Drug Combination Pilot Screening Identifies Synergistic Drug Combinations Effective against Patient-Derived and Drug-Resistant Melanoma Cell Lines.SLAS discovery : advancing life sciences R & D · 2021Article
- The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma.Cancers · 2021Review
- RTK Inhibitors in Melanoma: From Bench to Bedside.Cancers · 2021Review
- Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned so Far.Cancers · 2020Review
- Structure and Characterization of a Covalent Inhibitor of Src Kinase.Frontiers in molecular biosciences · 2020Article
- QT Interval Prolongation Associated With Cytotoxic and Targeted Cancer Therapeutics.Current treatment options in oncology · 2019Review
- SIRT2 Contributes to the Resistance of Melanoma Cells to the Multikinase Inhibitor Dasatinib.Cancers · 2019Article
- STAT3 enhances the constitutive activity of AGC kinases in melanoma by transactivating PDK1.Cell & bioscience · 2019Article
- Post-treatment de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma.BMC cell biology · 2018Article
- Synergistic anti-tumor effects of dasatinib and dendritic cell vaccine on metastatic breast cancer in a mouse model.Oncology letters · 2018Article
- Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.Current pharmaceutical design · 2017Review
- Targeting of BRAF resistant melanoma via extracellular matrix metalloproteinase inducer receptor.The Journal of surgical research · 2014Article
- Combination of dasatinib and gemcitabine reduces the ALDH1A1 expression and the proliferation of gemcitabine-resistant pancreatic cancer MIA PaCa-2 cells.International journal of oncology · 2014Article
- SRC family kinase inhibition as a novel strategy to augment melphalan-based regional chemotherapy of advanced extremity melanoma.Annals of surgical oncology · 2014Article
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Authors and funding
11 authors.
Funding
Abstract
backgroundSrc inhibitors sensitise melanoma cells to chemotherapy in preclinical models. The combination of dasatinib and dacarbazine was tested in a phase I trial in melanoma.
methodsPatients had ECOG performance status 0-2 and normal organ function. Dacarbazine was administered on day 1 and dasatinib on day 2 through 19 of each 21-day cycle. Both were escalated from 50 mg b.i.d. of dasatinib and 800 mg m(-2) of dacarbazine. Available pre-treatment biopsies were sequenced for BRAF, NRAS, and C-Kit mutations.
resultsDose-limiting toxicity was reached at dasatinib 70 mg b.i.d./dacarbazine 1000 mg m(-2), and was predominantly haematological. In 29 patients receiving dasatinib 70 mg b.i.d., the objective response rate (ORR) was 13.8%, the clinical benefit rate (ORR+SD) was 72.4%, the 6-month progression-free survival (PFS) was 20.7%, and the 12-month overall survival (OS) was 34.5%. Two out of three patients who were wild type for BRAF, NRAS, and c-KIT mutations had confirmed partial responses, and one had a minor response.
conclusionThe recommended phase II dose is dasatinib 70 mg b.i.d with dacarbazine 800 mg m(-2). PFS and OS data for dasatinib at 70 mg b.i.d. with dacarbazine compared favourably with historical controls. Preliminary data support evaluating tumour mutation status further as a biomarker of response.
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