Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stereotactic body radiation therapy (SBRT) delivers large doses of radiation with great accuracy, but is known to have deleterious effects on the vascular compartment of irradiated tissues. Combining SBRT with targeted anti-angiogenesis agents, while able to increase therapeutic efficacy, may unexpectedly precipitate vascular-based toxicities. In this report, we describe a patient with colon cancer who developed transverse myelopathy from regorafenib 2 years after receiving SBRT for three metastatic liver lesions. Regorafenib (Stivarga), formerly BAY 73-4506, (Bayer HealthCare Pharmaceuticals, Montville, NJ) is a multiple receptor tyrosine kinase inhibitor with anti-angiogenic effects used in metastatic colon cancer. Its most common side effects are fatigue, diarrhea and hypertension. However, severe neurologic toxicity has not been previously recognized. Here, we illustrate a case in which the patient developed hyperalgesia and radicular pain 2 weeks after starting regorafenib. Several studies report an increased neurological toxicity when angiogenesis inhibitors are given after radiation therapy, and we postulate that the angioinhibitory effects of regorafenib accelerated subclinical microvascular injury from SBRT. This unexpected toxicity may be clinically relevant when giving targeted angiogenesis inhibitors after SBRT.
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PMID:Regorafenib-induced transverse myelopathy after stereotactic body radiation therapy. 2543 37

Regorafenib (Stivarga, BAY 73-4506; Bayer Pharma AG, Berlin, Germany) is an oral multikinase inhibitor that targets the angiogenic tumor microenvironment and oncogenic kinases including vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR1, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), RAF, KIT, RET and BRAF. Its antiangiogenic effect is greater than that of its related drug, sorafenib. Regorafenib has been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (mCRC) in patients who have failed treatment with fluoropyrimidine, oxaliplatin and irinotecan based chemotherapy, an anti-VEGF therapy and, if KRAS wild type, an anti-EGFR therapy. The FDA based this approval on data from the CORRECT trial, which showed the efficacy of regorafenib compared with placebo. The most common grade 3-4 adverse reactions with the drug are hand foot skin reactions (HFSR), diarrhea, hypertension and fatigue. This review discusses the efficacy data, and the incidence and management of regorafenib's toxicities.
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PMID:Management of regorafenib-related toxicities: a review. 2632 19