Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Everolimus is a recently developed immunosuppressive drug for patients following solid organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of ciclosporin and tacrolimus and because of its lack of nephrotoxicity, it is a good alternative for calcineurin inhibitors in patients with renal dysfunction. In this paper we describe the case report of a 66-year-old caucasian female who underwent heart transplantation in December 2006. After induction with rabbit anti-thymocytic globulin, her immunosuppressive therapy comprised the combination of tacrolimus, mycophenolate mofetil (MMF) and steroids. Because of renal dysfunction, tacrolimus was changed for everolimus after 6 months. Unfortunately our patient developed severe stomatitis with aphthous ulcerations, shortly after the switch. Despite oral therapy (local anaesthetics), severe pain and malnourishment prompted interruption of everolimus and MMF and therapy was changed to ciclosporin and azathioprine. In addition, thalidomide was added. During the following weeks, there was progressive healing of the ulcerations. MMF was re-introduced and thalidomide was stopped after 6 weeks, without recurrent lesions after 4 months of follow-up.
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PMID:Severe stomatitis complicating immune-suppressive switch after cardiac transplantation. 2069 May 19

This multicenter, phase II trial evaluated the efficacy and safety of everolimus, an mTOR inhibitor, in patients with metastatic or recurrent bone and soft-tissue sarcoma after the failure of anthracycline- and ifosfamide-containing regimens. Everolimus was administered orally as 10 mg once daily. The primary endpoint was the progression-free rate (PFR) at 16 weeks, assessed by computed tomography scan according to RECIST v1.0. Between July 2010 and May 2011, 41 patients were enrolled in this study. Among them, 83% received two or more regimens of chemotherapy prior to study entry. In 38 patients who the primary endpoint was evaluable, 11 patients reached 16 weeks progression-free (one with partial response and 10 with stable disease), indicating a PFR at 16 weeks of 27% (95% confidence interval [CI], 16-42%). The PFR at 16 weeks was highest in patients with angiosarcoma (2 of 3, 67%). With a median follow-up of 10.9 months (range, 2.3-23.9 months) in living patients, the median progression-free survival was 1.9 months (95% CI, 1.3-2.4 months) and the median overall survival was 5.8 months (95% CI, 3.6-8.0 months). Most adverse events were generally mild and tolerable. Grade 3/4 toxicities included hyperglycemia (15%), stomatitis (7%), pain (5%), and asthenia (5%). Everolimus shows modest antitumor activity with manageable toxicities in heavily pretreated patients with bone and soft-tissue sarcoma.
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PMID:Multicenter phase II study of everolimus in patients with metastatic or recurrent bone and soft-tissue sarcomas after failure of anthracycline and ifosfamide. 2403 83

Skeletal metastases are an incurable complication afflicting the majority of patients who die from advanced breast cancer. They are most often osteolytic, characterized by net bone destruction and suppressed new bone formation. Life expectancy from first diagnosis of breast cancer bone metastases is several years, during which time skeletal-related events - including pain, fracture, hypercalcemia, and spinal cord compression - significantly degrade quality of life. The bone marrow niche can also confer hormonal and chemo-resistance. Most treatments for skeletal metastases target bone-destroying osteoclasts and are palliative. Recent results from the Breast cancer trials of Oral Everolimus-2 trial suggest that agents such as the mammalian target of rapamycin inhibitor everolimus may have efficacy against breast cancer bone metastases in part via stimulating osteoblasts as well as by inhibiting tumor growth. Selective estrogen receptor modulators similarly inhibit growth of estrogen receptor-positive breast cancers while having positive effects on the skeleton. This review discusses the future role of bone-anabolic agents for the specific treatment of osteolytic breast cancer metastases. Agents with both anti-tumor and bone-anabolic actions have been tested in the setting of multiple myeloma, a hematological malignancy that causes severe osteolytic bone loss and suppression of osteoblastic new bone formation. Stimulation of osteoblast activity inhibits multiple myeloma growth - a strategy that might decrease breast cancer burden in osteolytic bone metastases. Proteasome inhibitors (bortezomib and carfilzomib) inhibit the growth of myeloma directly and are anabolic for bone. Drugs with limited anti-tumor activity but which are anabolic for bone include intermittent parathyroid hormone and antibodies that neutralize the WNT inhibitors DKK1 and sclerostin, as well as the activin A blocker sotatercept and the osteoporosis drug strontium ranelate. Transforming growth factor-beta inhibitors have little tumor antiproliferative activity but block breast cancer production of osteolytic factors and are also anabolic for bone. Some of these treatments are already in clinical trials. This review provides an overview of agents with bone-anabolic properties, which may have utility in the treatment of breast cancer metastatic to the skeleton.
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PMID:Role of bone-anabolic agents in the treatment of breast cancer bone metastases. 2575 19

The angiomyolipoma of renal origin is a rare benign tumour composed of fat cells, smooth muscle cells, and thick-wall blood vessels. Mostly these are sporadic origin, asymptomatic and benign in nature. Here we present two cases of Renal angiomyolipoma (AML) presenting as fever, pain, perirenal haematoma & frank haematuria. After initial stabilization, evaluated by contrast enhanced computer tomography (CECT) & diagnosed as renal angiomyolipoma because of low Hounsfield areas (10-20HU) suggestive for fat. Patient later underwent angiography with selective angioembolisation. Post intervention period was uneventful and was treated by an oral Everolimus 10 mg daily for a period of one year in first case & partial resection was done in second case. On two year follow-up both patients were doing well & had normal renal function without any recurrence. Embolisation is the emergency treatment of choice for bleeding angiomyolipoma. When preventive treatment is considered a nephron sparing approach by either transarterial embolisation or partial nephrectomy is clearly important. While angiomyolipoma in both kidneys or in solitary functioning kidneys, renal preservation is mandatory in order to avoid need for renal replacement therapy. Also, recently approved drug Everolimus may be considered for patients not suitable for surgery particularly in tumour seen with tuberous sclerosis.
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PMID:A Case Series & Review of Literature of Angiomyolipoma with Medical & Surgical Perspective. 2650 Sep 47

Everolimus was very effective in the treatment of Anne, a patient with TSC and renal angiomyolipomas. Anne's renal tumors continue to shrink in size, with a decrease of more than 50% achieved to date, and her GFR remains in the normal range. She no longer experiences chronic back pain due to kidney tumors and is not taking pain medications. She is active and able to exercise daily, and her blood pressure remains within normal limits. Usually diagnosed in childhood, TSC requires life-long management. Patients can have many manifestations of the disease, and nurses need to be made aware of them because they often play a critical role in educating patients and their families (Agricola et al., 2013). Currently, there is a great need for education and awareness in the medical field regarding TSC. The disease is often overlooked, misdiagnosed, or mismanaged. Patients can be given misleading information, which may lead to unnecessary procedures and distress. Moreover, with the correct management, patients with TSC have a normal life expectancy and preserved renal function.
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PMID:Tuberous Sclerosis Complex: One Woman's Search for Renal-Preserving Therapy. 2659 Dec 74

We report a case of a patient treated with everolimus and exemestane combination therapy for bone metastasis after breast surgery.The patient, a 58-year-old woman, consulted our department for back pain in October 2014.S he was diagnosed with left breast cancer when she was 41 years old.She had received Bt+Ax for left breast cancer and administered tamoxifen for 5 years.We decided on everolimus and exemestane combination therapy after observing an abnormal uptake in the 7th to 8th thoracic vertebrae on a PET-CT scan.The pain was controlled using oxycodone and fentanyl orally disintegrating tablet with zoledronic acid.After receiving treatment, the patient experienced pruritus and a Grade 2 rash, but they were managed with antihistamine administration and the treatment was continued.Four months later, the abnormal uptake on the right thoracic vertebrae shrunk; the pain almost disappeared, and oxycodone and fentanyl orally disintegrating tablet were discontinued.Subsequently, exemestane was used alone.Six months later, the range of abnormal uptake on the thoracic vertebrae progressed, and the disease was evaluated as PD.Four months later, everolimus and exemestane combination therapy was resumed, and the abnormal uptake on the thoracic vertebrae almost disappeared as observed on a PET scan.The effectiveness of the treatment was evaluated as CR because other local recurrence and new metastases were not found. Everolimus might exhibit bone resorption inhibiting effects and bone protection effects, but the decision regarding the periods of suitable use and the effects of long-term continuation of treatment are controversial, and further discussion based on experience of increasing use is required.
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PMID:[A Case of Recurrent Breast Cancer with Bone Metastasis Successfully Treated with Everolimus and Exemestane Therapy]. 2822 74