Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A progress report is presented on two on-going clinical trials in women with advanced breast cancer. In Trial I to date, 56 patients have been randomized to tamoxifen (TAM) alone or TAM plus aminoglutethimide (AG) (plus hydrocortisone). Patients failing TAM can then receive AG. The two groups are reasonably well balanced with respect to prior hormonal therapy exposure (TAM, 19%; TAM plus AG, 17%), age, disease-free interval, performance score, and estrogen receptor status. The TAM plus AG group has a higher incidence of visceral dominant disease (41 versus 26%) and prior chemotherapy exposure (41 versus 33%). Responses have been observed in 7 of 27 (26%) patients on TAM and 11 of 28 (39%) on TAM plus AG. Median times to treatment failure (defined as disease progression, unacceptable toxicity, or patient refusal) are 211 and 123 days, respectively (log-rank on time to treatment failure, p = 0.87). Toxicity is greater for TAM plus AG with a higher incidence of skin rash, lethargy, and dizziness. Thrombotic events were seen in one patient on TAM and two patients on TAM plus AG. One patient on TAM plus AG developed leukopenia and sepsis. The data are too preliminary for one to draw firm conclusions regarding relative efficacy. In TRial II to date, 35 patients with prior tamoxifen exposure have received AG. The mean number of prior systemic therapies is 3.2 (range, 1 to 7). The response rate is 20% and similar with (21%) or without (19%) prior chemotherapy exposure. The median time to treatment failure is 92 days. One patient developed leukopenia and sepsis. Additional patient accrual is necessary to allow characterization of potential efficacy within prognostically important subsets.
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PMID:Progress report on two clinical trials in women with advanced breast cancer. Trial I: tamoxifen versus tamoxifen plus aminoglutethimide. Trial II: aminoglutethimide in patients with prior tamoxifen exposure. 704 29

This phase 1 study evaluated the safety and tolerability of adjuvant treatment with subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF) administered in combination with escalating doses of thalidomide in patients with surgically resected stage II (T4), III, or IV melanoma at high risk for recurrence. Adjuvant treatment included GM-CSF 125 microg/m2 subcutaneously for 14 days and thalidomide at an initial dose of 50 mg/d, escalated in cohorts of 3 to 6 patients each to a maximum of 400 mg/d followed by 14 days of rest. Treatment was continued for up to 1 year in the absence of disease progression. Of 19 patients treated, the most common toxicities were grade 1/2 constipation (68%), fatigue (58%), neuropathy (42%), bone and joint pain (37%), and dyspnea, dizziness, injection site skin reaction, and somnolence (32% each). Thrombotic events in 3 of 19 patients (16%), including 1 treatment-related death, were the most serious adverse events and were thought to be due to thalidomide. With a median follow-up of 945 days (2.6 y), 8 (42%) patients were alive, including 1 with disease and 7 without evidence of disease. GM-CSF plus thalidomide as adjuvant therapy for patients with resected high-risk melanoma was associated with a high incidence of thrombotic events. Because life-threatening events are unacceptable in the adjuvant setting, up-front antithrombotic prophylaxis will be necessary for further evaluation of GM-CSF plus thalidomide as a viable regimen in this patient group.
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PMID:A phase 1 study of granulocyte macrophage colony-stimulating factor (sargramostim) and escalating doses of thalidomide in patients with high-risk malignant melanoma. 1930 96

Plasma cell dyscrasias are characterized by a malignant clonal proliferation of plasma cells. Due to the excessive production of abnormal clonal gammaglobulins, or paraproteins, there are major hemorheologic changes in the circulation. As a result, clinical manifestations of the hyperviscosity syndrome become a major cause of morbidity and mortality. Pathogenic factors for the hyperviscosity are due both to increased plasma viscosity and to increased erythrocyte aggregation, leading to increased whole blood viscosity. These changes are dependent on the plasma concentration as well as the molecular size of the paraprotein with the threshold for onset of hyperviscosity for IgG >15 g/dl, for polymerized IgG3 >4-5 g/dl, for IgA >10-11 g/dl; for polymerized IgA >6-7 g/dl and for IgM >3 g/dl. Correspondingly, the incidence of symptomatic hyperviscosity in Waldenstrom's macroglobulinemia is 10-30%, while that in IgG myeloma is 2-6%. Clinically, the syndrome has neurologic features of headache and dizziness, visual changes, renal failure, and cardiac failure from increased plasma volume. Thrombotic complications are frequent. Paradoxically, there can be bleeding complications due to impairment of platelet function. Removal of the paraprotein by plasma exchange (plasmapheresis) can effectively reduce the hyperviscosity. Long-term control of paraprotein production can be achieved by chemotherapy. The early recognition of the symptoms of hyperviscosity, confirmed by laboratory findings of increased paraproteins and of increased blood viscosity, is essential for the proper management of this group of disorders.
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PMID:Hyperviscosity in plasma cell dyscrasias. 2345 37