Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efficacy and safety of high dose administration of NK 622 (toremifene citrate) were studied in tamoxifen (TAM)--failed patients with breast cancer. The patients included in the study were the following failure cases in TAM therapy: unresponded cases in TAM therapy (TAM unresponded cases), temporary responded (CR, PR) but progressed cases in TAM therapy (TAM temporary responded cases), and those relapsing during TAM adjuvant therapy or within 6 months after the adjuvant therapy (TAM adjuvant failed cases). NK 622 of a 120 mg/day dose were orally given daily once at least for 8 weeks. The response rates in evaluable cases were 6.3% (1/16) in TAM unresponded cases, 11.1% (1/9) in TAM temporary responded cases, 15.4% (4/26) in TAM adjuvant failed cases, and 11.8% (6/51) in total cases including 1 CR and 5 PR cases. Long NC in which duration of NC maintained for more than 6 months was observed in 18.8% (3/16) of TAM unresponded cases, 22.2% (2/9) of TAM temporary responded cases, 11.5% (3/26) of TAM adjuvant failed cases, and 15.7% (8/51) of total cases. Rates of response and long NC were 14.3 and 19.0% in postmenopausal patients with estrogen receptor positive cancer, respectively. A median value of duration to the onset of response was 34 days (15-137). Median duration of response and long NC were 127 days (39-381) and 238.5 days (178-281), respectively. Adverse effects were experienced in 3 (5.1%) of 59 patients: nausea in 1, vertigo in 1 and increase of GOT, GPT, LDH and gamma-GTP in another 1. The side effects were moderate and reversible. From these results, NK 622 seems to become a safe and effective drug for TAM-failed patients with breast cancer by using a 120 mg/day dose.
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PMID:[Efficacy and safety of high dose NK 622 (toremifene citrate) in tamoxifen failed patients with breast cancer]. 842 90

Case Report on a Breast Cancer Patient: A description of medical history, diagnosis and therapy of a patient with breast cancer is presented. The patient showed primary symptoms of vertigo and truncal and gait ataxia. The cause of this cerebellar disorder was a paraneoplastic cerebellar degeneration (PCD) characterized by anti-Purkinje cell antibodies (anti-Yo) directed against specific epitops shared by Purkinje and tumour cells. The presence of these antibodies in some patients suggests an autoimmune mechanism, although their role in pathogenesis has not been established. Usually malignancies of the breast and the ovaries are associated with anti-Yo positive PCD. The intensive search for the underlying neoplasma led to the identification of a malignant tumour of the right breast. Tumour excision of subsequent immunosuppressive treatment resulted in a progression of PCD. Antibody titers remained nearly unchanged during the course of the disease.
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PMID:[Paraneoplastic cerebellar degeneration: case report of a patient with breast carcinoma]. 868 88

A 44-year-old male presented with a solitary cerebellopontine angle (CPA) metastasis from lung cancer. His initial symptoms were vertigo and hearing loss beginning 5 months after the diagnosis of the primary cancer. Two months later, right facial paresis developed. His neurological deterioration was rapid. Magnetic resonance (MR) imaging with enhancement disclosed the CPA tumor. The tumor was partially removed through the retroauricular retromastoid approach. Histological examination of the specimen revealed adenocarcinoma. The characteristic rapidly progressive symptoms and MR imaging with enhancement are the most sensitive and essential examinations for this lesion.
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PMID:Solitary metastasis of lung cancer to the cerebellopontine angle--case report. 886 54

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

Paraneoplastic cerebellar degeneration is a rare remote effect of ovarian and breast carcinoma especially, and is characterised clinically by rapidly evolving pancerebellar symptoms. A woman aged 83 developed progressive vertigo, cerebellar ataxia, nystagmus and dysarthria. The cerebrospinal fluid showed slight mononuclear pleocytosis, elevated total protein and IgG concentrations, and oligoclonal bands. A magnetic resonance investigation performed within the first month of symptoms was normal. A left pelvic mass was found, possibly a carcinoma of the colon or the left ovary. Cancer antigen 125 was elevated in the serum and antibodies against Purkinje cells (anti-Yo antibodies) were demonstrated in the serum and cerebrospinal fluid. These results suggested a carcinoma of the ovary as primary site of cancer. Autopsy revealed a left ovarian adenocarcinoma and marked loss of Purkinje cells in the cerebellum. The case illustrates that anti-Yo antibodies may serve as a marker not only for paraneoplastic cerebellar degeneration, but also for the nature of the neoplasm that caused it.
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PMID:[Paraneoplastic cerebellar degeneration. A case report]. 934 Aug 52

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.
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PMID:Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991). 963 13

Paraneoplastic cerebellar degeneration (PCD) is a clinical syndrome and known to be occasionally associated with small cell carcinoma of the lung (SCLC). PCD usually affects patients before the cancer is evident. The disorder evolves subacutely, and causes severe pancerebellar dysfunction. In this paper, we report a case of PCD associated with SCLC. A 65-year-old man presenting with 2 weeks of progressive vertigo, gait ataxia, and speech disturbance, was readmitted to our hospital. He had earlier been given a diagnosis of SCLC, oat cell carcinoma, and had undergone high-dose chemotherapy with peripheral blood stem cell transplantation during his first admission. Following that treatment regimen, the tumor disappeared completely and the patient had been in remission. Based on neurological findings and the presence of anti-neuronal antibodies a diagnosis of PCD was made. Although cyclophosphamide (500 mg/m2) was administered, the patient experienced no relief of his cerebellar ataxia. Six months afer readmission, he died of cardiac tamponade due to malignant pericarditis. A histological examination at autopsy found few Purkinje cells and a proliferation of Bergmann's astrocytes in the cerebellar cortex. These findings were consistent with the diagnosis of PCD.
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PMID:[A case of paraneoplastic cerebellar degeneration associated with small cell lung cancer]. 1021 46

A Phase I study of angiogenesis inhibitor TNP-470 was conducted in patients with advanced cancer. TNP-470 (25-235 mg/m2) was administered i.v. over 4 h once a week to patients who had solid tumors refractory to the best available treatment or with a high risk of recurrence and who had normal renal, hepatic, and hematological function and no evidence of coagulopathy. The aims of the study were to determine the maximum tolerated dose, dose-limiting toxicities (DLTs), and the pharmacokinetics of TNP-470 given on a once-weekly schedule. Thirty-six patients, ages 23-75 (median, 54 years), with an Eastern Cooperative Oncology Group performance status of 0-2 were treated. The number of patients at each dose level (mg/m2) were 6 (25), 3 (50), 3 (75), 3 (100), 3 (133), 12 (177), and 6 (235). The principal toxicities of TNP-470 were dizziness, lightheadedness, vertigo, ataxia, decrease in concentration and short-term memory, confusion, anxiety, and depression, which occurred at doses of 133, 177, and 235 mg/m2. Two patients treated at 235 mg/m2 experienced DLT in the form of grade III cerebellar neurotoxicity after 6 weeks of treatment. Overall, these neurological symptoms were dose-related, had an insidious onset, progressively worsened with treatment, and resolved completely within 2 weeks of stopping the drug. One patient with malignant melanoma had stabilization of the previously growing disease for 27 weeks while on the treatment. Two patients, one with adenocarcinoma of the colon and the other with a soft tissue sarcoma, had no clinically detectable disease but were at high risk for recurrence at the initiation of treatment and received 13 months and > 3 years of treatment, respectively, with no evidence of disease recurrence. The remaining patients had progression of their disease after 1-6 months of treatment. The mean plasma half-life (t(1/2)) of TNP-470 and its principal metabolite, AGM-1883, were extremely short (harmonic mean, t(1/2) of 2 and 6 min, respectively) with practically no drug detectable in the plasma by 60 min after the end of the infusion. MII, an inactive metabolite, had a considerably longer t(1/2) of approximately 2.6 h. Mean peak TNP-470 concentrations were > or = 400 ng/ml at doses > or = 177 mg/m2. On the basis of this study, the maximum tolerated dose of TNP-470 administered on a weekly schedule was 177 mg/m2 given i.v over 4 h. The principal DLT was neurotoxicity, which appeared to be dose-related and was completely reversible. On the basis of the short plasma t(1/2) of TNP-470, exploration of a prolonged i.v. infusion schedule is warranted.
Clin Cancer Res 1999 Aug
PMID:A Phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer. 1047 76

Paraneoplastic cerebellar degeneration (PCD) is the most frequently seen paraneoplastic syndrome affecting the brain. PCD is most commonly associated with cancers of the ovary, breast, and lung. The anti-Purkinje cell antibodies (anti-Yo) that specifically damage the Purkinje cells of the cerebellum are found in the patient's serum and cerebrospinal fluid. The typical presentation of PCD includes limb and truncal ataxia, often along with dysarthria. This report describes the case of a 47-year-old woman without significant medical history who developed new onset of unsteady gait, headache, and vertigo. The imaging studies suggested rhombencephalitis. The patient initially responded to corticosteroid treatment. Unfortunately, her gait ataxia worsened and she developed dysarthria, neither of which responded to increasing dosages of corticosteroids. Extensive imaging studies showed no evidence of tumor, but the patient was found to have positive anti-Yo antibodies and elevated cancer antigen 125 (CA-125). Pathology results from exploratory laparotomy revealed stage III C adenocarcinoma of the ovary. This case demonstrates that PCD may be the presenting symptom of an occult malignancy. The pathogenesis, diagnosis, and treatment of PCD, and its rehabilitation implications, are reviewed.
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PMID:Paraneoplastic cerebellar degeneration as the first evidence of cancer: a case report. 1085 34

TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostate cancer. In early clinical reports, TNP-470 is tolerated up to 177 mg/m(2) with neurotoxic effects (fatigue, vertigo, ataxia, and loss of concentration) being the principal dose limiting toxicity (DLT). Terminal half-life values are short and have shown intermittent and intrapatient variation (range: 0.05 - 1.07 h). Recently, mechanistic studies have identified cell cycle mediators and the protein methionine aminopeptidase-2 (MetAP-2) as molecular targets of TNP-470 and fumagillin. Animal studies confirm some toxic effects on normal angiogenic processes such as the female reproductive system and wound healing, which will require caution and close monitoring in the clinic. TNP-470 is one of the first anti-angiogenic compounds to enter clinical trials, making it a valuable prototype for future trials of angiogenesis inhibitors in oncology.
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PMID:TNP-470: an angiogenesis inhibitor in clinical development for cancer. 1106 Jul 50


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