ArticleBritish journal of cancer2012
Targeting the endothelin axis with atrasentan, in combination with IFN-alpha, in metastatic renal cell carcinoma.
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 10 papers, 2 of them syntheses 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
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Integrative meta-analysis identifies microRNA-regulated networks in infantile hemangioma.BMC medical genetics · 2016Pooled it
- Incidence and risk of hypertension with ramucirumab in cancer patients: a meta-analysis of published studies.Clinical drug investigation · 2015Pooled it
- Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800).Clinical genitourinary cancer · 2015Trial
- Endothelin and the tumor microenvironment: a finger in every pie.Clinical science (London, England : 1979) · 2024Review
- 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications.Oncotarget · 2017Review
- Hippo signaling mediates proliferation, invasiveness, and metastatic potential of clear cell renal cell carcinoma.Translational oncology · 2014Article
- Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell carcinoma: role of the mTORC1/2 and hypoxia-inducible factor pathways.Cell death & disease · 2013Article
- Endothelin 1 in cancer: biological implications and therapeutic opportunities.Nature reviews. Cancer · 2013Review
- The association of IFI27 expression and fatigue intensification during localized radiation therapy: implication of a para-inflammatory bystander response.International journal of molecular sciences · 2013Article
- Trial Watch: Immunostimulatory cytokines.Oncoimmunology · 2013Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe endothelin system is involved in tumour growth. Atrasentan, a selective endothelin-A-receptor antagonist, blocks endothelin signalling. This phase I trial studied combining treatment of interferon-alpha (IFN-α) with atrasentan in renal cell carcinoma (RCC). PATIENTS AND
methodsThis study evaluated the safety and tolerance of IFN-α (9MU subcutaneously (s.c.) three times a week) in combination with atrasentan (2.5, 5 and 10 mg orally once daily) in untreated metastatic RCC. Cohort 10 mg was extended to obtain insights in efficacy and pharmacodynamics.
resultsObserved toxicities mainly consisted of known IFN-like toxicities (anorexia, chills, fever, fatigue and nausea), and of nasal congestion (associated to atrasentan). None of these toxicities were considered dose limiting. Cohort 10 mg was extended up to 32 patients; in a subset of patients treated according to the protocol (n=27), median overall survival (OS) was 17.3 months. One patient (3.1%) showed a partial response lasting 14.3 months. In an exploratory analysis, we observed that in the subset of patients with declining vascular endothelial growth factor (VEGF) levels (in combination with rising Endothelin-1 levels), median OS was 22.2 months compared with 2.2 months in patients with increasing VEGF levels.
conclusionCombination treatment of IFN-α 9MU-α s.c. three times a week and atrasentan 10 mg once daily is tolerated. Clinical activity, especially OS, and biomarkers in our view warrant further studies targeting the endothelin axis.
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