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)

To evaluate the therapeutic effects and systemic toxicities of a capecitabine-based home therapy regimen in patients with metastatic renal cell carcinoma, 30 patients were enrolled in a phase II clinical trial. Treatment consisted of oral capecitabine combined with subcutaneous recombinant human interferon-alpha 2a, recombinant human interleukin-2 and oral 13-cis-retinoic acid. There were two (7%) complete responses (CRs) and eight (27%) partial remissions (PRs), for an overall objective response rate of 34% (95% CI 17-53%). Except one, all responses are ongoing, with a median duration of 9+ and 8+ months for CRs and PRs, respectively. Additionally, 12 patients (40%) reached stable disease. Eight patients (27%) showed continued disease progression despite treatment. Therapy was well tolerated and was given in the outpatient setting. Capecitabine-related World Health Organization (WHO) grade 2 and 3 toxicities were observed in five and two patients respectively, and were limited to fatigue, nausea/vomiting, diarrhoea, stomatitis, dermatitis and hand-and-foot syndrome. The substitution of capecitabine for 5-FU in the pre-existing biochemotherapy regimen did not result in a reduced therapeutic efficacy and showed significant anti-tumour activity in patients with advanced renal cell carcinoma.
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PMID:Capecitabine in the treatment of metastatic renal cell carcinoma. 1094 96

The efficacy of combined interferon-alpha and ribavirin was studied in interferon-naive hepatitis C patients. Results show that reduced liver inflammation was more likely in combination therapy, as were reductions in liver enzyme levels and HCV clearance from the blood. Adverse effects using combination therapies were similar to those using interferon-alpha alone. Patients using combination therapy experienced greater nausea. Bone marrow suppression was also recorded. Overall, the relapse rate appears to be reduced when ribavirin is included in the treatment. However, while there was improvement in disease condition from using combination therapy, many subjects did not respond positively. A longer-lasting form of interferon is currently being tested.
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PMID:Combination therapy for hepatitis C. 1136 30

In this adjuvant three-arm multicenter trial, we studied whether modulating the standard 5-fluorouracil (5-FU) treatment with either folinic acid (FA) or interferon-alpha-2a (IFN-alpha) was superior to the recommended standard of adjuvant treatment in R0 resected colon cancer, 5-FU plus levamisole (LEV) for 12 months, in terms of toxicity and outcome. From July 1992 to October 1999, a total of 813 patients with resected colon cancer in stage II (T4N0M0; n = 63) or stage III (TxN1-3M0; n = 750) were randomized into three treatment groups and stratified according to N stage and participating centers (64 hospitals). The patients received a postoperative loading dose of 5-FU (450 mg/m2 on days 1 to 5 [arms A and C]) or 5-FU (450 mg/m2) plus FA (Rescuvolin, Medac, Hamburg, Germany, 200 mg/m2 on days 1 to 5 [arm B]). After completion of the first chemotherapy cycle, LEV was administered orally at a dosage of 150 mg per day on days 1 to 3, once every 2 weeks. After a 4-week chemotherapy-free interval, the treatment was continued weekly for 52 weeks. Treatment in one arm A ("standard") (n = 279) consisted of 5-FU intravenously (450 mg/m2 on day 1, once a week) plus LEV. 5-FU plus LEV was modulated in arm B (n = 283) with FA (200 mg/m2 on day 1, once a week) and in arm C (n = 251) with IFN-alpha at 6 million units three times a week repeated weekly. Treatment dosages were adjusted if toxic events above WHO grade 2 occurred. Patients were closely followed to determine recurrence and survival; the latter was calculated according to Kaplan-Meier analysis. Toxic events above WHO grade 2, mainly leukopenia, diarrhea, and nausea, occurred in 113 (14%) of 649 patients who had completed treatment in arms A (8.4%), B (13.5%), and C (31.7%). Discontinuance rates were as follows: 28% for all patients, 29% in arm A, 21% in arm B, and 34% in arm C. Overall relapse rates were 27% for all patients, 30% in arm A, 24% in arm B, and 28% in arm C. Relapses were local (8%), distant (78%), or combined (12%). Four-year overall survival rates in arms A, B, and C were 66.1%, 77.5%, and 66.2%, respectively. The 4-year survival rate in arm B was significantly higher compared to arm A (P <0.02, log-rank test) with arm A being equal to arm C. Adjuvant therapy with 5-FU plus FA plus LEV for 12 months is superior to the recommended standard (5-FU + LEV for 12 months). IFN-alpha modulation of 5-FU (plus LEV) adds to the toxicity with no therapeutic benefit.
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PMID:Toxicity and effects of adjuvant therapy in colon cancer: results of the German prospective, controlled randomized multicenter trial FOGT-1. 1141 51

Treatment options for patients with metastatic renal cell carcinoma are limited. Interferon-alpha has an overall response rate of 10-15% in phase II and III clinical trials and is considered a standard option for patients. Though the anti-estrogen toremifene has shown only modest single agent activity in renal cell carcinoma, evidence for synergy of anti-estrogens with interferon-alpha exists in renal cell and other cancers. Therefore, a phase II trial was undertaken to test the combination of interferon-alpha and toremifene in advanced renal cell carcinoma. Thirteen patients with measurable metastatic or unresectable local disease were treated with interferon-alpha at a dose of 5 million units/m2 three times a week and daily oral toremifene at 300 mg daily in divided doses. Patients were treated for 12 weeks and then restaged. Clinical response was the primary endpoint of the trial. Four patients (31%) had evidence of stable disease at 12 weeks, while the remaining nine patients (69%) progressed on treatment. Toxicity was moderate, with grade 2 or 3 fatigue, nausea and anorexia each noted in 31% of patients. We conclude that the combination of interferon-alpha plus toremifene demonstrates no significant activity in advanced renal cell carcinoma.
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PMID:A phase II trial of interferon-alpha and toremifene in advanced renal cell cancer patients. 1190 38

Systemic mastocytosis (SM), as opposed to cutaneous-only mastocytosis, implies the presence of neoplastic mast cell infiltration in extracutaneous tissue. Mast cell disease in adults is often systemic and often involves the bone marrow. Typical clinical and laboratory features of SM include urticaria pigmentosa, mast cell mediator symptoms (eg, headache, flushing, lightheadedness, urticaria and pruritus, nausea, diarrhea, abdominal pain, and vasodilatory shock), bone pain (eg, osteoporosis, lytic bone lesions, and fractures), hepatosplenomegaly, cytopenia, eosinophilia, elevated serum tryptase and histamine, and bone marrow fibrosis and angiogenesis. SM may be indolent (no evidence of organ dysfunction), aggressive (presence of organ dysfunction), associated with another often chronic myeloid hematologic disease (SM-AHD), or present as mast cell leukemia or sarcoma. Mast cell-mediator symptoms are treated with histamine antagonists and cromolyn sodium. Indolent SM does not require cytoreductive therapy. Aggressive SM and SM-AHD are managed based on their molecular profile. Recent information suggests that FIP1-like-1-platelet-derived growth factor receptor-alpha(+) SM responds well to imatinib mesylate, whereas interferon-alpha should be considered as a first-line treatment in all of the other cases, including patients with Asp816Val(+) SM. Cladribine has been shown to be effective in patients who develop resistance to interferon treatment.
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PMID:Systemic mastocytosis: current concepts and treatment advances. 1508 68

The prognosis for patients with metastatic renal cell carcinoma (RCC) remains unsatisfactory to date. Combined immunochemotherapy (ICT) strives for a synergistic effect avoiding a substantial increase of therapy-related adverse events. The combination therapy regimes consisting of either interferon-alpha-2a/vinblastine (IFN-alpha2a/VBL) or interferon-alpha-2a/interleukin-2/5-fluorouracil (IFN-alpha2a/IL-2/5-FU) demonstrated objective remission rates, surpassing the results obtained with the administration of single immunotherapeutic agents. Despite the data from a recently published study, the role of these two therapy combinations did not seem clearly defined. Therefore, we compared the impact of IFN-alpha2a/VBL and IFN-alpha2a/IL-2/5-FU on remission and survival as well as the safety profile in a retrospective study in patients with metastatic RCC. In a retrospective single-center study, 105 patients with metastatic RCC having received treatment between 1992 and 2002 with either s.c. IFN-alpha2a/ i.v. VBL ( n=70, group 1) or s.c. IFN-alpha2a/ s.c. IL-2/ i.v. 5-FU ( n=35, group 2) were evaluated. At a median follow-up of 17 months, remission and survival rates as well as the toxicity profiles of the respective groups were documented and compared. The median age throughout the entire patient population was 61 years. Patients in the IFN-alpha2a/VBL group reached a median overall survival of 20 months compared to 17 months for the patients in the IFN-alpha2a/IL-2/5-FU population ( p=0.850). The objective response rate in the first patient group reached 25.7%, whereas the tumor remission rate of group 2 amounted to 22.9% ( p=0.680). Patients showing an objective response reached a significantly higher survival rate than patients without response reaction (median survival was 36 vs 10 months, p=0.0001). The incidence of each therapy-induced adverse event was higher throughout the second treatment group. These differences were significant with respect to flu-like symptoms (85.7 vs 57.1%, p=0.003), grade 3/4 elevations of liver enzymes (14.3 vs 1.4%, p=0.007), nausea/vomiting (74.3 vs 50%, p=0.017), the severity of erythemas (74.3 vs 10%, p<0.001), and patients with lung edema (17.1 vs 2.9%, p=0.009). Eight patients discontinued the ICT, two of whom died of a myocardial infarction.Despite an overall limited prognosis, patients showing a tumor remission seem to benefit from ICT in terms of overall survival. While both treatment options offer comparable remission and survival rates, the IFN-alpha2a/VBL regimen induces fewer adverse events than the treatment with IFN-alpha2a/IL-2/5-FU.
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PMID:[Impact of immunochemotherapy on survival of patients with metastatic renal cell carcinoma. A retrospective study comparing interferon-alpha-2a/vinblastine versus interferon-alpha-2a/interleukin-2/5-fluorouracil]. 1523 86

Immunochemotherapy consisting of interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and gemcitabine (GEM) for metastatic renal cell carcinoma. A partial response maintained for 15 months, was obtained in one case resistant to IFN-alpha and IL-2 of para-aortic lymph node metastases (case 1). A minor response with 30% reduction of lung metastasis was obtained in one IFN-alpha resistant case, and the duration was 6 months (case 2). In one case, in contra-lateral renal metastasis, no disease progression was obtained for 6 months (case 3). One case with resistance to IFN-alpha and IL-2, and who had preoperative abnormalities of corrected serum calcium, serum c-reactive protein and hemoglobin, had progressive disease and died of cancer after 6 months (case 4). Grade 3 toxicity was noted in leucopenia (4/4), anemia (1/4), and nausea/ vomiting (1/4). Although the response duration was short, the combination immunochemotherapy consisting of IFN-alpha, IL-2 and GEM may be a promising salvage regimen for the patients with metastatic renal cell carcinoma.
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PMID:[Active combination immunochemotherapy with interferon-alpha, interleukin-2 and gemcitabine for four patients with metastatic renal cell carcinoma]. 1585 69

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

We report on a randomised trial that aimed to compare the efficacy of continued daily prednisolone treatment during the entire induction phase, with prednisolone given for 2 weeks of each cycle in combination with VMCP (vincristine, melphalan, cyclophosphamide, prednisolone)-interferon-alpha 2b (IFN-alpha 2b) treatment in 299 previously untreated elderly patients (median age: 67 years) with multiple myeloma. After completion of induction treatment patients were randomised to IFN-alpha 2b with or without prednisolone, thrice weekly. Response rate was 62% in the continuous and 60% in the control arm (intent to treat analysis, P=0.81). Progression-free survival [median: 20 months vs. 19 months; hazard ratio (HR): 0.99, 95% confidence interval (CI): 0.74-1.33, P=0.97] and overall survival (median: 34 months vs. 37 months; HR: 1.16, 95% CI: 0.85-1.59, P=0.35) were similar in both groups. Reduced performance status (Eastern Cooperative Oncology Group, grades 2-4) was the predominant risk factor for poor survival followed by age >65 years, high beta2-microglobulin, and impaired renal function. There was more grades 3-4 dyspnoea and cardiac impairment and grades 1-2 hyperglycaemia, but less nausea, emesis and anaemia in patients on continuous prednisolone therapy. In conclusion, continuing prednisolone treatment during the entire duration of the induction phase with VMCP-IFN-alpha 2b did not improve outcome.
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PMID:Continuous prednisolone versus conventional prednisolone with VMCP-interferon-alpha2b as first-line chemotherapy in elderly patients with multiple myeloma. 1622 52

Thrombocytopenia is one of the common manifestations of systemic lupus erythematosus (SLE). Its treatment consists of corticosteroids and/or other immunosuppressive drug such as azathioprine, vincristine, cyclosporine, and mycophenolate mofetil. Common adverse reactions of immunosuppressive treatment are infections, hematologic and liver function abnormalities, but neurologic complications may also be seen. Reversible posterior leukoencephalopathy syndrome (RPLS) is a syndrome manifested by headache, nausea, vomiting, seizures, cortical blindness, and visual disturbances. Neuroimaging shows bilateral subcortical and cortical edema with prominent posterior distribution. Moreover, treatment with immunosuppressive drugs such as cyclosporine, cisplatin, tacrolimus, and interferon-alpha can induce a condition resembling RPLS. We report a case of a young woman with SLE and thrombocytopenia, who developed severe perspiration, headache, and seizure after receiving cyclosporine. A brain magnetic resonance image showed multiple high signal intensities on T2-weighted images predominantly located at the parietooccipital lobe. The patient recovered completely clinically and radiologically after discontinuing cyclosporine.
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PMID:Reversible posterior leukoencephalopathy syndrome in systemic lupus erythematosus with thrombocytopenia treated with cyclosporine. 1727 58


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