Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bevacizumab (Avastin) in combination with intravenous 5-fluorouracil-based chemotherapy as first-line as well as second-line treatment of metastatic colorectal cancer improves survival. Although skin rash (type unspecified) has been described in some patients following infusion of bevacizumab, it is not a common toxicity of bevacizumab, while acneiform rash occurs in more than 90% of patients who receive cetuximab (Erbitux), the severity of which appears to be predictive of response. We report a patient with colorectal cancer who developed a rash secondary to bevacizumab that correlated with response. A 40-year-old patient with stage IV colorectal cancer received FOLFOX-4 and bevacizumab, which he tolerated very well except for a skin rash related to bevacizumab. The rash cleared every time bevacizumab was eliminated from the chemotherapy regimen. When use of bevacizumab was resumed, similar rash reappeared. Therefore, we believe that this observation of the rash emergence was linked to bevacizumab administration. The most common toxicities associated with bevacizumab include hypertension, hemorrhage, gastrointestinal perforation, arterial thromboembolism, wound healing and proteinuria. Exfoliative dermatitis and a nonspecific rash have been reported with bevacizumab. This case report, we believe, is the first report of a possible correlation between a rash and a positive drug response associated with bevacizumab, and may initiate further investigation of similar observation.
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PMID:Skin rash secondary to bevacizumab in a patient with advanced colorectal cancer and relation to response. 1707 24

Despite recent advances in chemotherapy, including the development of irinotecan and oxaliplatin, survival of patients with advanced colorectal cancer remains suboptimal. Thanks to an increased understanding of the biologic basis of cancer, investigators are turning to molecularly targeted therapy to further improve outcome. Current research in colorectal cancer focuses on inhibiting the epidermal growth factor receptor and vascular endothelial growth factor. Both are essential to tumor growth and frequently over-expressed in colorectal cancer cells. Epidermal growth factor receptor pathways promote survival of tumor cells through cell proliferation, differentiation, migration, adhesion, and transformation and inhibition of apoptosis, whereas the vascular endothelial growth factor is a key mediator of angiogenesis and may have other biologic roles. Recent phase II and III results show the feasibility and activity of inhibiting both by using monoclonal antibodies in combination with chemotherapy in patients with advanced colorectal cancer. Cetuximab (an epidermal growth factor receptor antibody) plus irinotecan yields an increased overall response in patients with irinotecan-refractory colorectal disease. In previously untreated patients, irinotecan/5-fluoruoracil/leucovorin plus cetuximab also generates an increased overall response rate. Randomized trials of the humanized anti-vascular endothelial growth factor antibody (rhuMAb vascular endothelial growth factor) plus chemotherapy yielded increased overall response rates and median survival times compared with chemotherapy alone. The primary toxicity of cetuximab is an acneform skin rash; rhuMAb vascular endothelial growth factor causes mild hypertension and may cause perturbations in coagulation. Treatment with either does not appear to exacerbate chemotherapy-related toxicity.
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PMID:Emerging therapies for metastatic colorectal cancer: focus on EGFR and VEGF inhibition. 1978 Feb 48

The spectrum of cardiac side-effects of cancer chemotherapy has expanded with the development of combination, adjuvant and targeted chemotherapies. Their administration in multiple regimens has increased greatly, including in older patients and in patients with cardiovascular and/or coronary artery disease (CAD). Cardiac toxicity of anthracyclines involves oxidative stress and apoptosis. Early detection combines 2D-echocardiography and/or radionuclide angiography and recent methods such as tissue Doppler imaging, strain rate echocardiography and sampling of serial troponin and/or NT-proBNP levels. Dexrazoxane has proven effective in the prevention of dose-related toxicity in children and adults. High doses of the alkylating drugs cyclophosphamide and ifosfamide may result in a reversible heart failure and in life-threatening arrhythmias. Myocardial ischemia induced by the antimetabolites 5-fluorouracil and capecitabine impacts prognosis of patients with prior CAD. Severe arrhythmias may complicate administration of microtubule inhibitors. Targeted therapies with the antibody-based tyrosine kinases (TK) inhibitors trastuzumab and, to a lesser extent, alemtuzumab induce heart failure or asymptomatic LV dysfunction in 1-4% and 10%, respectively. Cetuximab and rituximab induce hypotension, whereas bevacizumab may promote severe hypertension and venous thromboembolism. Small molecule TK inhibitors may also elicit LV dysfunction, in only few patients treated with imatinib mesylate, but in a substantially higher proportion of those receiving the multitargeted TK inhibitor sunitinib or the recently approved drugs erlotinib, lapatinib and dasatinib. Management of patients at increased cardiovascular risk associated with advancing age, previous CAD or targeted therapies may be optimized by referral to a cardiologist in a cross-specialty teamwork.
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PMID:Cardiac side-effects of cancer chemotherapy. 2039 20

Bevacizumab and cetuximab both improve treatment efficacy when administered with chemotherapy for metastatic colorectal carcinoma (mCRC). Cetuximab has enhanced efficacy in Kras wild-type tumors. However, inferior outcomes have been demonstrated concerning the concurrent use of bevacizumab and cetuximab with chemotherapy. There is an urgent need to define the optimal sequence of use of these two agents. With regard to the pre-clinical data that increased VEGF expression is associated with acquired resistance to anti-EGFR antibody, we performed a retrospective analysis on the outcomes of patients who received bevacizumab-containing regimens after cetuximab failure in Kras wild-type mCRC. From January 2006 to December 2011, patients who received bevacizumab-containing regimens for mCRC in our institution were reviewed. Patients were eligible for further analysis if the following criteria were met: i) Kras wild-type mCRC; ii) chemotherapy and cetuximab received as immediate prior treatment; iii) chemotherapy and bevacizumab received as the index line of treatment; and iv) imaging conducted for response evaluation. Outcome measures included median progression-free survival (mPFS) and objective response rate (ORR). Targeted adverse events were recorded in accordance with two prospective observational cohort studies; the BRiTE and BEAT studies. Fifty patients who received bevacizumab-containing regimens were reviewed and 18 of them met the criteria for further analysis. After a median follow-up of 12.1 months, the mPFS for the total group of patients was 26.3 weeks (95% CI, 19.5-33.0 weeks) with an ORR of 38.9%. Two patients (11.1%) had hypertension that required additional anti-hypertensive drugs and one patient did not survive due to a bowel perforation. No arterial thromboembolic events (ATEs), post-operative wound-healing complications (POWHCs) or grade III/IV bleeding were observed. In patients with Kras wild-type mCRC, bevacizumab-containing regimens following cetuximab failure have modest activity and manageable toxicity.
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PMID:Bevacizumab-containing regimens after cetuximab failure in Kras wild-type metastatic colorectal carcinoma. 2342 May 87

With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.
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PMID:Renal Toxicities of Targeted Therapies. 2592 90