ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Phase I study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Pooled it
- Inefficiencies and Patient Burdens in the Development of the Targeted Cancer Drug Sorafenib: A Systematic Review.PLoS biology · 2017Pooled it
- Trial
- Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma: A Phase 2 Clinical Trial.JAMA oncology · 2016Trial
- BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma--A Trial of the ECOG-ACRIN Cancer Research Group (E2804).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02.Neuro-oncology · 2012Trial
- Two drug interaction studies of sirolimus in combination with sorafenib or sunitinib in patients with advanced malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Trial
- The Complex Role of MAPK/ERK Signaling Pathway in Different Types of Thrombocytopenia.Current issues in molecular biology · 2025Review
- DeepTraSynergy: drug combinations using multimodal deep learning with transformers.Bioinformatics (Oxford, England) · 2023Article
- Combined VEGFR and MAPK pathway inhibition in angiosarcoma.Scientific reports · 2021Article
- Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.Frontiers in molecular biosciences · 2020Review
- Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations.The oncologist · 2020Article
- Evolving Significance and Future Relevance of Anti-Angiogenic Activity of mTOR Inhibitors in Cancer Therapy.Cancers · 2017Review
- Potential therapeutic targets of epithelial-mesenchymal transition in melanoma.Cancer letters · 2017Review
- Quercetin as an Emerging Anti-Melanoma Agent: A Four-Focus Area Therapeutic Development Strategy.Frontiers in nutrition · 2016Review
- Sorafenib-based combined molecule targeting in treatment of hepatocellular carcinoma.World journal of gastroenterology · 2015Review
- Article
- Large-scale automatic extraction of side effects associated with targeted anticancer drugs from full-text oncological articles.Journal of biomedical informatics · 2015Article
- MEK and PI3K inhibition in solid tumors: rationale and evidence to date.Therapeutic advances in medical oncology · 2015Review
- Targeting drivers of melanoma with synthetic small molecules and phytochemicals.Cancer letters · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeThis phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma. PATIENTS AND
methodsPatients with stage IV or unresectable or recurrent stage III melanoma and Eastern Cooperative Oncology Group performance status of 0 to 1 were eligible. Sorafenib was given orally once or twice daily and temsirolimus was given i.v. weekly, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per Response Evaluation Criteria in Solid Tumors criteria. Consenting patients with accessible tumors underwent optional tumor biopsies before treatment and after the second infusion of temsirolimus. Tumor biopsies were analyzed for activating mutations in BRAF and NRAS, and for expression of P-extracellular signal-regulated kinase (P-ERK) and P-S6 proteins.
resultsA total of 25 patients were accrued to the study. The maximum tolerated doses were sorafenib 400 mg every morning and 200 mg every evening and temsirolimus 25 mg i.v. weekly. Dose-limiting toxicities included thrombocytopenia, hand-foot syndrome, serum transaminase elevation, and hypertriglyceridemia. There were no complete or partial responses with the combination; 10 patients achieved stabilization of disease as their best response. The median progression-free survival was 2.1 months. Matching pretreatment and day 15 tumor biopsies showed marked inhibition of P-S6 with treatment in 3 of 4 evaluable patients, but minimal inhibition of P-ERK.
conclusionsCombination therapy with sorafenib and temsirolimus resulted in significant toxicity at higher dose levels, failed to achieve any clinical responses in genetically unselected patient population, and did not inhibit P-ERK.
Indexed as
Identifiers
What OpenQuestion holds
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.