Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bellini duct carcinoma accounts for 1-3% of all renal carcinomas and is characterized by an aggressive course and extremely poor prognosis. Conventional treatment for renal-cell carcinoma seems to be ineffective. Since the histology of Bellini duct carcinoma is similar to urothelial carcinoma, chemotherapy for urothelial cancer might be more promising than conventional treatment. We present a patient with renal carcinoma of the left kidney who underwent laparoscopic extrafascial nephrectomy and adrenalectomy. Histopathologic work-up showed Bellini duct carcinoma (pT3a, NX, G3, R0 and M0). Eight months after surgery, disease progression was observed with local recurrence, multiple pulmonal lesions, para-aortic and aortocaval lymphadenopathies and a solitary bone lesion. First-line treatment with interferon-alpha and interleukin-2, as well as second-line treatment with thalidomide, were ineffective. Disease progressed rapidly and the patient experienced a dramatic reduction in performance status and quality of life. Six courses of chemotherapy with cisplatin and gemcitabine were given, a treatment reported to be highly active in urothelial cancer. The treatment was well tolerated, with thrombopenia WHO grade II, anemia WHO grade I and nausea/vomitus WHO grade II being the most severe side effects. Follow-up computer tomography revealed partial remission with 50-100% response at the different sites of metastasis. This response was accompanied by a dramatic improvement in performance status (from an initial 60% to 100% Karnofsky index) and quality of life. The combination of cisplatin and gemcitabine was highly active in this patient with metastatic Bellini duct carcinoma, even given as third-line treatment. This regimen fulfils all criteria for palliative treatment, as our patient showed an impressive improvement in WHO performance status and therefore in quality of life. Histopathologic characteristics should be a major criterion for treatment strategy in renal carcinoma, particularly in Bellini duct carcinoma.
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PMID:Major response and clinical benefit following third-line treatment for Bellini duct carcinoma. 1598 94

Seventeen patients with locally advanced or metastatic renal cell carcinoma (RCC) were enrolled in this phase II trial. The purpose of the trial was to assess the efficacy of the administration of oral GD0039, and to further assess the pharmacokinetics and pharmacodynamics of this drug. Patients were given an initial dose of 37.5 micro g/kg b.i.d for 3 weeks followed by one week off in each cycle, with the treatment continuing until disease progression or adverse effects. All 17 patients discontinued treatment due to disease progression or toxicity. Adverse events such as fatigue, nausea and diarrhea were common but generally mild. No evidence of anti-tumor activity of GD0039 was seen in this study.
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PMID:Phase II study of the efficacy and safety of oral GD0039 in patients with locally advanced or metastatic renal cell carcinoma. 1603 17

At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on treatment. With this weekly schedule of administration, and in the doses studied, MEDI-522 seems to be without significant toxicity, may have effects on tumor perfusion, and may have clinical activity in renal cell cancer. These findings suggest the MEDI-522 could be further investigated as an antiangiogenic agent for the treatment of cancer.
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PMID:Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion. 1627 8

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated on a Phase II trial with imatinib. Eligible patients had histologically confirmed RCC, metastatic and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), Karnofsky performance status (KPS) of at least 70%, life expectancy of more than 3 months, and adequate hematological, renal, and liver function. Imatinib was given orally at a dose of 400 mg bid. The most common toxicities were Grade II/III nausea (28%) and Grade II renal insufficiency (14%). All patients had tumor tested by immunohistochemistry (IHC) for KIT protein (CD117, DAKO). One tumor (7%) demonstrated strong, diffuse expression and the rest were negative. No complete or partial responses were observed in 12 evaluable patients treated with imatinib.
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PMID:Phase II trial of imatinib (Gleevec) in patients with metastatic renal cell carcinoma. 1638 Aug 35

DNA methyltransferases (DNMTs) methylate DNA, promoting local chromatin condensation and consequent repression of gene expression. The purpose of this two-stage phase II trial was to assess the antitumor activity of MG98, a second generation antisense oligodeoxynucleotide inhibitor of human DNMT 1, in patients with metastatic renal carcinoma (MRC). Untreated adult patients with measurable MRC were treated with MG98 at a dose of 360 mg/m2 via 2-h iv infusion twice weekly for three consecutive weeks out of four. The primary endpoint was objective response or absence of progression for at least eight weeks. Pharmacokinetics and DNMT1 mRNA levels in peripheral blood mononuclear cells (PBMCs) were also analyzed at pre-specified intervals. Seventeen eligible patients received a median of two cycles of treatment (range, 1-7), and no objective responses were seen. Nine patients had progressive disease, six had stable disease, and the study was stopped after the first stage. The most common symptomatic toxicities were rigors, fatigue, fever, and nausea. Hematological toxicity was mild. Seven patients treated with prior nephrectomy had grade 3 or 4 elevations in hepatic transaminases. Significantly higher Cmax and AUC(0-->inf) values were observed in these patients. No conclusive pattern of decreased DNMT1 activity in PBMCs was detected post MG98 treatment. The lack of objective responses observed may be explained by a lack of target effect or the choice of tumor type. Transaminitis was observed in patients with prior nephrectomy and appeared to be associated with altered drug exposure in these patients.
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PMID:Phase II trial of DNA methyltransferase 1 inhibition with the antisense oligonucleotide MG98 in patients with metastatic renal carcinoma: a National Cancer Institute of Canada Clinical Trials Group investigational new drug study. 1650 49

In a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity.
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PMID:A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma. 1728 37

Triapine is a novel small molecule ribonucleotide reductase inhibitor that showed activity in renal cell carcinoma (RCC) cell lines. Evaluating new agents with novel mechanisms remains of interest for patients with incurable RCC. This was a single-arm, multicentre phase II trial where Triapine was given at a schedule of 96 mg/m2 2-h infusion daily x 4 repeated every 2 weeks in patients with recurrent RCC. A median of four cycles of Triapine was administered to 19 eligible patients. One response was seen (7%.) Median time to progression was 3.6 months. Common adverse events (AEs) were grade 1-2, with fatigue in 74%, nausea in 68% and vomiting in 58%. However grade 3/4 neutropenia was seen in 79% and acute reactions of hypoxia, hypotension, methemoglobinemia were seen. Dose reductions/delays due to AEs were common with only 47% of patients receiving > 90% of planned dose intensity. The study closed, at the end of stage 1 as it did not meet the minimal efficacy criteria to proceed. Further evaluation of Triapine at this dose and schedule in patients with advanced kidney cancer is not recommended.
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PMID:Phase II study of Triapine in patients with metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC IND.161). 1739 73

The aim of this study was to evaluate prospectively post-radiofrequency ablation (RFA) syndrome and to determine its effect on the quality of life in the 15 days after percutaneous RFA treatment. We carried out an internal review board-approved prospective study of the delayed symptoms that occurred after 71 consecutive RFA sessions in 53 patients (12 women and 41 men; age range 45-83 years; mean age 71.6 years) with 45 primary liver tumours, 34 liver metastases, 3 renal cell carcinoma (RCC), 2 residual lesions from RCC after nephrectomy and 1 pancreatic metastases from RCC. Postablation symptoms occurred in 17 of 53 (32%) patients. Six of 17 patients developed low-grade fever (from 37.5 to 38.5 degrees C). Other symptoms included delayed pain (9/17), nausea (7/17), vomiting (3/17), malaise (3/17) and myalgia (1). Postablation syndrome is a common phenomenon after RFA of solid abdominal tumours. Not only in our study but also in the previous ones the occurrence is observed in approximately one-third patients. Patients should be informed that these symptoms are self-limiting after RFA and most patients should be able to resume near-complete preprocedural levels of activity within 10 days after the procedure.
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PMID:Post-radiofrequency ablation syndrome after percutaneous radiofrequency of abdominal tumours: one centre experience and review of published works. 1795 90

A 71-year-old man, with a history of metastatic renal cell cancer (RCC), presented with symptoms of a small bowel obstruction with nausea, vomiting, cramps, and diarrhea. He underwent surgery and was found to have intraluminal metastases from his metastatic RCC. Intraluminal metastases are rare and usually present with obstruction, bleeding, or perforation. The mainstay of treatment remains complete surgical excision, even in the face of widely metastatic disease. Surgery not only palliates symptoms, but may also extend survival because metastatic RCC can be a very indolent and unpredictable disease. Furthermore, these patients can now be treated with a new class of antiangiogenic agents that are showing impressive response rates, which may also translate into improved overall survival.
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PMID:A case of small bowel obstruction due to intraluminal metastases from metastatic renal cell cancer. 1830 52

A case of synchronous adrenocortical carcinoma (ACC) and renal cell carcinoma (RCC) has not yet been described in the English medical literature, to our knowledge. We report a first such case of adrenocortical and renal cell carcinomas occurring simultaneously in a 53-year-old male. He presented with history of vague abdominal pain. Ultrasound followed by a computed tomography (CT) scan and a magnetic resonance imaging (MRI) examination revealed a 6.4 cm left adrenal mass and a 3.5 cm right renal mass. The patient had complaints of gastroparesis manifesting with constant nausea as well as intermittent abdominal bloating and abdominal pain. He also had history of profuse intermittent sweating. There was no history of palpitations or fluctuations in blood pressure. The patient's urinary vanillylmandelic acid (VMA) levels and serum cortisol levels were normal. His 24-hour urine metanephrine levels were slightly elevated. Left adrenalectomy and right partial nephrectomy were performed. In this case, it is important to determine whether these tumors represent metastases or two synchronous tumors, as this has implications on the patient's management and prognosis. Clinical and pathological clues that led to the diagnosis are discussed in detail.
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PMID:Synchronous renal cell carcinoma and adrenocortical carcinoma: a rare case report and clinicopathologic approach. 1840 53


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