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)

Patients with newly diagnosed gliomas were treated with adoptive transfer of ex vivo activated T lymphocytes, derived from lymph nodes (LNs) draining autologous tumor vaccines, to determine the long-term toxicity of this treatment. Twelve consecutive patients were enrolled: 2 with grade II astrocytoma, 4 with anaplastic gliomas, and 6 with glioblastoma multiforme. Patients were injected intradermally with short-term cultured autologous irradiated tumor cells, admixed with granulocyte macrophage colony-stimulating factor, to stimulate draining LNs. The LN cells were activated with staphylococcal enterotoxin A for 48 h and then cultured in medium containing interleukin 2 for an additional 6-8 days and subsequently transferred i.v. to the patients. The number of cells obtained from the LNs ranged from 9 x 10(7) to 1.1 x 10(9), and the median cell proliferation was 41-fold. The dose of T cells infused ranged from 0.6 to 5.5 x 10(10) with a median of 1.1 x 10(10), the majority of which were CD 4+ (mean, 71%). The entire treatment was performed as outpatient therapy and was associated with a toxicity of grade 2 or less, consisting mainly of fever, nausea, and myalgias during the first 24 h. There were no indications of late adverse events from this treatment even among three patients with follow-up greater than 2 years post T cell transfer. Moreover, four patients demonstrated partial regression of residual tumor. This Phase I clinical trial of adoptive immunotherapy for patients with newly diagnosed malignant gliomas demonstrates feasibility, lack of long-term toxicity, and several objective clinical responses.
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PMID:T cell adoptive immunotherapy of newly diagnosed gliomas. 1087 70

Although the efficacy of the nitrosourea-based combination chemotherapy procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, and vincristine (PCV) has been previously demonstrated in the setting of anaplastic/intermediate-grade gliomas, the benefit for glioblastoma patients remains unproven. In the current study, we sought to determine whether the addition of alpha-difluoromethylornithine (eflornithine), an inhibitor of ornithine decarboxylase, which has shown encouraging results in the setting of recurrent glioma patients, to a nitrosourea-based therapy (PCV) would constitute a more effective adjuvant therapy in the treatment of glioblastoma multiforme patients in the postradiation therapy setting. Following conventional radiation therapy, 272 glioblastoma (GBM) patients were randomized to receive either alpha-difluoromethylornithine-PCV (DFMO-PCV; 134 patients) or PCV alone (138 patients), with survival and time to tumor progression being the primary endpoints. The starting dosage of DFMO was 3.0 g/m2 p.o. q8h for 14 days before and after treatment with N-(2-chloroethyl)-N-cyclohexyl-N-nitrosurea; PCV was administered as previously described1. Clinical and radiological (Gadolinium-enhanced MRI) follow-ups were nominally at the end of each 6 or 8 week cycle (PCV at 6 weeks; DFMO-PCV at 8 weeks). Laboratory evaluations for hematologic and other adverse effects were at 2 week intervals. There was no difference in median survival or median time-to-tumor progression between the two treatment groups, as measured from day of commencement of postradiotherapy chemotherapy [MS (months): DFMO-PCV, 10.5; Overall survival, as measured from time of tumor diagnosis at first surgery, was 13.3 and 14.2 months at the median and 6.2 and 8.7% at 5 years, respectively, for the DFMO-PCV and PCV arms. The treatment effect was unchanged after adjustment for age, performance status (KPS), extent of surgery, and other factors using the multivariate Cox proportional hazard model. Adverse effects associated with DFMO consisted of gastrointestinal (diarrhea nausea/vomiting), cytopenias, and minimal ototoxicity (limited to tinnitus) at the dose range tested. The addition of DFMO to the nitrosourea-based PCV regimen in this phase III study demonstrated no additional benefit in glioblastoma patients, underscoring the resistance of glioblastoma multiforme tumors to alkylating agents. For patients with anaplastic (intermediate grade) gliomas, in which the previously demonstrated benefit of post-radiation chemotherapy is more substantial, the evaluation of DFMO-PCV vs. PCV is still ongoing and hopefully will yield more encouraging results.
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PMID:Phase III randomized study of postradiotherapy chemotherapy with alpha-difluoromethylornithine-procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, vincristine (DFMO-PCV) versus PCV for glioblastoma multiforme. 1105 Dec 33

A case is reported of glioblastoma multiforme (GM) of the cerebellum associated with an intracerebellar hemorrhage. A 54-year-old male was admitted to our hospital with sudden onset of headache and nausea. CT scan showed right intracerebellar hemorrhage. The patient received conservative therapy and was discharged without any neurological deficits. However a second cerebellar hemorrhage attacked him ten days after discharge. His level of consciousness deteriorating, he underwent suboccipital craniectomy and the hematoma with the surrounding elastic tissues was excised. There were no findings suggesting hemorrhage within the tumor on the preoperative neuroimagings, but histological examination confirmed GM with massive hemorrhage. To our knowledge, only 2 cases of cerebellar GM with massive hemorrhage have been reported in the literature. Our case indicates cerebellar GM should be taken into account as a possible cause of cerebellar hemorrhage.
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PMID:[A case of cerebellar glioblastoma with massive cerebellar hemorrhage]. 1179 54

This phase II study in recurrent high-grade glioma evaluated the response rate, toxicities, and time to treatment failure of high-dose carboplatin modulated by a 24-h infusion of thymidine (75 g/m(2)). The trial was based on preclinical data and a prior phase I study ( J. Clin. Oncol. 17, 2922-2931, 1999); a phase II recurrent high-grade glioma study was initiated in July of 1998. Thymidine was given over 24 h; carboplatin was given over 20 min at hour 20 of the thymidine infusion. The starting dose of carboplatin had a value of 7 for the area under the curve (AUC), with allowance for dose escalation of 1 AUC unit per cycle if grade 2 toxicity was observed. Treatment cycles were repeated every 4 weeks. Accrual as of September 1999 was 45 patients [4 were unevaluable]: 76% with glioblastoma multiforme (GBM), 20% with anaplastic oligodendroglioma, 2% with mixed type, and 2% with anaplastic astrocytoma. Most patients had prior chemotherapy (78%). As observed in the earlier phase I study (in which carboplatin pharmacokinetics were unaltered by thymidine or antiseizure medications), thymidine was myeloprotective, resulting in a minimal need for dose reduction for patients having a >2 grade toxicity (in only 4% of the courses of treatment). Of 101 total courses, the number of courses (at the AUCs) was 3 (5), 4 (6), 58 (7), 20 (8), 11 (9), and 5 (10). Grade 3 nonhematologic toxicities included headache (4%), altered consciousness (3%), fatigue (1%), and nausea (3%). Responses included 2 partial (1 oligodendroglioma, 1 GBM; 5%); 3 minor (1 anaplastic astrocytoma, 2 GBM; 7.3%); 6 stable disease (14.6%); and 30 progressive disease (73.2%). For GBM patients, median survival was 23 weeks (with a 95% confidence interval of 20 to 50 weeks), and progression-free survival was 8 weeks (with a 95% confidence interval of 7-16 weeks). These results in GBM were comparable to other phase II GBM trials and thus do not represent a therapeutic advance in the treatment of GBM. Taken collectively, however, results are consistent with continued investigation of thymidine in combination with chemotherapeutic agents for high-grade glioma and other malignant diseases. The significant myeloprotection afforded by thymidine may have particular relevance to polychemotherapeutic regimens.
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PMID:A phase II trial of thymidine and carboplatin for recurrent malignant glioma: a North American Brain Tumor Consortium Study. 1191 2

A 56-year-old male with DM and HTN presented with flank pain and nausea. Review of systems was negative, physical examination was notable for mild hypovolemia and laboratory revealed BUN 51 mg/dl, creatinine (Cr) 5.1 mg/dl (baseline 1.5), Westergren ESR 122 mm/h, fractional excretion of sodium 0.2% and UA positive for blood and protein. Despite volume resuscitation the Cr continued to rise. Urine sediment analysis revealed granular casts, renal tubular epithelial cells and a negative Hansel's stain. Hemodialysis was initiated with Cr 13.7 mg/ dl for dyspnea and dysgeusia. Subsequent laboratory data revealed 2 separate positive anti-GBM antibody titers and prednisone therapy was initiated. Renal biopsy was performed for further diagnostic, therapeutic and prognostic information and demonstrated interstitial nephritis with linear IgG and albumin deposition consistent with diabetic nephropathy. Follow-up antibody titers were negative. prednisone was discontinued and Cr stabilized with conservative therapy. Anti-GBM antibody disease is characterized by circulating IgG antibodies directed against the glomerular basement membrane, specifically the alpha-3 (IV) collagen chain. Anti-GBM nephritis is a rapidly progressive, isolated glomerulonephritis in association with circulating anti-GBM antibodies. A positive immunofluorescence (IF) test is considered diagnostic in the appropriate clinical setting. Therapies include immunosuppressive agents to suppress new antibody production and plasmapheresis to eliminate circulating antibodies. Anti-GBM antibody is not rapidly cleared by steroid therapy and the recovery of renal function is rare if initiation Cr is greater than 7 mg/dl. This case demonstrates that the current ELISA for alpha-3 (IV) collagen is not pathognomonic for anti-GBM nephritis and that renal biopsy with IF for IgG and albumin may be indicated to prevent administration of potentially toxic treatment.
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PMID:Diabetic nephropathy with interstitial nephritis presenting with a false-positive anti-GBM antibody. 1203 99

Although many patients with oligodendrogliomas (ODs) and oligoastrocytomas (OAs) benefit from a combination of surgery and adjuvant radiotherapy, most patients eventually experience recurrence of their disease. Recent evidence has shown that ODs are more chemosensitive than other gliomas, including astrocytomas or glioblastoma multiforme. These initial findings have prompted further study of chemotherapy in treating ODs and mixed OAs. Advances in molecular genetic analysis have led to improvements in predicting response to chemotherapy and prognosis for ODs, OAs, and astrocytomas. Pure ODs are more chemosensitive than mixed ODs. This difference is related to different proportions of 1p/19q loss of heterozygosity in these neoplasms. Therefore, genetic analysis is likely to be key in determining appropriate treatment. The most common first-line chemotherapy for patients with OD is a procarbazine, lomustine, and vincristine (PCV) combination regimen. However, this regimen is associated with cumulative myelosuppression, nausea, vomiting, and weight loss. Therefore, other chemotherapy agents and regimens have been investigated. Perhaps the most promising is temozolomide, a novel alkylating agent that freely crosses the blood-brain barrier. Temozolomide is approved in the United States for the treatment of recurrent anaplastic astrocytomas and in Europe for any recurrent high-grade gliomas. Initial reports suggest that temozolomide is effective in treating ODs as first- and second-line chemotherapy. Unlike the PCV regimen, temozolomide is not associated with cumulative myelosuppression and is usually well tolerated. Further studies are needed to confirm the efficacy and safety profile of temozolomide and to determine the optimal dose and schedule for treating ODs.
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PMID:Recent developments in the molecular characterization and treatment of oligodendroglial tumors. 1267 85

A 74-year-old man was diagnosed with cerebellar glioblastoma multiforme (GBM). He initially presented with headache, nausea, vomiting, and truncal ataxia. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a round mass with ring enhancement in the vermis of the cerebellum. Subtotal removal of tumour was performed, and the pathological diagnosis was cerebellar glioblastoma multiforme. Subsequently, radiochemotherapy was performed. GBM of the cerebellum is rare and only accounts for a small fraction of all GBM. To our knowledge, there have only been 7 cases of senile cerebellar GBM reported. Our patient is one of the oldest cases recorded in the Asian literature.
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PMID:Glioblastoma multiforme of the cerebellum in an elderly man. 1536 8

Extracranial bone metastasis from glioblastoma multiforme (GBM) has rarely been reported in the literature, and most metastatic GBMs are multiple bone metastases. The authors describe the first case of a GBM with metastasis only to the axis. This 42-year-old man presented with a 2-month history of headache, nausea, vomiting, and disorientation. Magnetic resonance imaging demonstrated a right temporal tumor, which was diagnosed as a GBM based on tumor resection. The patient was treated using radiation (6000 cGy) and the intravenous administration of nimustine hydrochloride. Eighteen months thereafter, he experienced the sudden onset of neck pain. Magnetic resonance studies revealed a tumor in the axis that was diagnosed as GBM based on biopsy procedure.
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PMID:Glioblastoma multiforme metastasis to the axis. Case report. 1579 92

We studied the activity of T138067-sodium in patients with malignant gliomas. T138067-sodium is a unique new chemotherapy agent that inhibits microtubule formation by binding irreversibly and specifically to beta(1), beta(2)and beta(4) isotypes of 3-tubulin, causing cell arrest at G(2)/M and inducing apoptosis. Patients with recurrent anaplastic astrocytoma or glioblastoma multiforme were treated intravenously with 330 mg/m(2) of T138067-sodium weekly. Treatment was continued until the patient experienced either unacceptable toxicity or progressive disease. Patients had to have histologically proven glioma, have bidimensionally measurable disease at least 1 cm x 1 cm, and have received no more than one prior adjuvant chemotherapy. No chemotherapy or radiotherapy for recurrent disease was permitted. Nineteen patients entered the trial. One patient was found to be ineligible. There were two patients with anaplastic astrocytoma and 16 with glioblastoma multiforme. Only two patients had received prior adjuvant chemotherapy. The first seven patients had full pharmacokinetic sampling. No dose-limiting toxicity was seen, and pharmacokinetic results were consistent with those from nonglioma patients. The most common drug-related effects were fatigue (33%), nausea (28%), neutropenia (28%), and anorexia (17%). No patients stopped the study because of toxicity. No responses were seen in the 15 eligible patients who completed at least one cycle. Three patients had stable disease with a median duration of 2.6 months. Our results suggest that given in this dose and schedule T138067-sodium does not have activity in this population of anaplastic astrocytoma and glioblastoma multiforme.
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PMID:Phase 2 study of T138067-sodium in patients with malignant glioma: Trial of the National Cancer Institute of Canada Clinical Trials Group. 1583 Dec 36

On March 15, 2005, the U.S. Food and Drug Administration approved temozolomide (Temodar capsules, Schering-Plough Research Institute) for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment. Five hundred seventy-three glioblastoma multiforme patients were randomized to receive either temozolomide + radiotherapy (n = 287) or radiotherapy alone (n = 286). Patients in the temozolomide + radiotherapy arm received concomitant temozolomide (75 mg/m2) once daily for the duration of radiation therapy (42-49 days). This was followed, 4 weeks later, by six cycles of temozolomide, 150 or 200 mg/m2 daily for 5 days, every 4 weeks. Patients in the control arm received radiotherapy only. In both arms, radiotherapy was delivered as 60 Gy/30 fractions to the tumor site with a 2 to 3 cm margin. Pneumocystis carinii pneumonia prophylaxis was required during temozolomide + radiotherapy treatment and was continued until recovery of lymphocytopenia (Common Toxicity Criteria grade <1). At disease progression, temozolomide salvage treatment was given to 161 of 282 patients (57%) in the radiotherapy alone arm, and to 62 of 277 patients (22%) in the temozolomide + radiotherapy arm. Patients receiving concomitant and maintenance temozolomide + radiotherapy had significantly improved overall survival. The hazard ratio was 0.63 (95% confidence interval, 0.52-0.75; log-rank, P < 0.0001). Median survival was 14.6 months (temozolomide + radiotherapy) versus 12.1 months (radiotherapy alone). Adverse events during temozolomide treatment included thrombocytopenia, nausea, vomiting, anorexia, constipation, alopecia, headache, fatigue, and convulsions.
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PMID:Food and Drug Administration Drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. 1620 62


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