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)

We performed an open, nonrandomized, multicenter phase-II trial to evaluate the efficacy and toxicity of 1 year of treatment with the oral iron chelator deferiprone in 38 mainly nonthalassemic patients with transfusional iron overload. Initial serum ferritin varied between 996 and 11.644 micrograms/l. Patients were treated with 3-6 g of deferiprone daily. Mean urinary iron excretion (UIE) in 36 evaluable patients was 21.0 mg/24 h and was significantly higher in the patients with thalassemia than in those with myelodysplasia. Negative iron balance was achieved in 20 patients (56%). The median duration of treatment was 10 months; due to side effects and other causes only 20 patients completed 1 year of treatment. Mean serum ferritin levels decreased from 3563 micrograms/l at the start of the trial to 2767 micrograms/l at 6 months (26 patients, p < 0.004) and to 2186 micrograms/l at 12 months (20 patients, p < 0.005). Serum ferritin levels normalized in two patients who were no longer transfusion dependent. Deferiprone was clearly not effective in three patients (two with myelofibrosis, one with myelodysplasia). One patient with myelodysplasia developed agranulocytosis after 12 months of treatment; this was rapidly reversible after stopping deferiprone. Three patients had a mild and transient decrease in white blood cell count. Other side effects leading to withdrawal from the trial consisted mainly of nausea (3 patients), arthralgia (2), and skin rash (1). No clinical signs of zinc deficiency were seen, although zinc excretion was increased in three patients. No changes were seen in liver enzymes, creatinine, antinuclear factor, T-cell subsets, cardiac function, visual acuity, and audiogram. Although our results confirm deferiprone as an effective iron chelator in patients with thalassemia and in some patients with other forms of iron overload, there is still some concern about the safety of this drug, which therefore, at this time, should be used exclusively in well-controlled clinical trials.
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PMID:Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. 895 43

In studies conducted by the Eastern Cooperative Oncology Group, treatment with either paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) or carboplatin was associated with an improvement in 1-year survival in patients with stage IV non-small cell lung cancer (NSCLC). Based on these findings, a phase II trial of carboplatin plus paclitaxel was conducted in patients with advanced NSCLC to determine the activity and toxicity of this regimen. Eligibility requirements included stage IIIB or IV histologically confirmed NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, no prior chemotherapy, and adequate hematologic, renal, hepatic, and cardiac functions. Paclitaxel was administered intravenously over 24 hours at a dose of 135 mg/m2 (28 patients) or 175 mg/m2 (23 patients), followed by a 1-hour infusion of carboplatin on day 2. Carboplatin was administered at a dose of 300 mg/m2 (16 patients) or, using the Calvert formula, a dose calculated to achieve an area under the concentration-time curve of 6 mg/mL x min (35 patients). Treatment was repeated every 28 days for a total of six cycles. Among the 51 eligible patients, 34 were men and 17 were women; their median age was 60 years and their median Eastern Cooperative Oncology Group performance status was 1. Six patients had stage IIIB and 45 had stage IV disease. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3% of treatment cycles, respectively. The most common nonhematologic toxicities noted included nausea and emesis, neuropathy, and arthralgia and myalgia. There were no complete responses and 14 partial responses, for an overall response rate of 27% (95% confidence interval, 17% to 41%). Median survival was 38 weeks and the survival rate at 1 year was 32%. Paclitaxel plus carboplatin, as given in this study, was found to be a moderately active regimen in patients with advanced NSCLC. This regimen warrants comparison with existing cisplatin-based regimens in a prospective randomized trial.
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PMID:Paclitaxel plus carboplatin in the treatment of patients with advanced lung cancer: a Vanderbilt University Cancer Center phase II trial (LUN-46). 900 20

We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (> or = 7.5 x 10(8) nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day -2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 micrograms/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 micrograms/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 x higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day -2 (median, 2.26 x 10(8)/kg nucleated cells [range, 1.7 to 3.3 x 10(8)/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to > or = 500/microL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34(+)-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34(+)-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P < or = .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of approximately 2.26 x 10(8)/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34(+)-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier "sacrificial" reinfusion of approximately 2 x 10(8)/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.
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PMID:Effect of CD34+ selection and various schedules of stem cell reinfusion and granulocyte colony-stimulating factor priming on hematopoietic recovery after high-dose chemotherapy for breast cancer. 905 32

We have conducted a clinical and pharmacokinetic trial of the novel podophyllotoxin derivative NK611 administered orally for 21 consecutive days. The treatment was repeated every 35 days. Eighteen patients were included into the study, all of whom were eligible. Due to early progression of tumor disease in two patients, 16 patients were evaluable for toxicity [7 female, 9 male, median age 64 years (range: 44 to 73)]. Dose escalation steps were 5 mg/day [105 mg per cycle (pc)], 10 mg/day (210 mg pc), 12.5 mg/day (265 mg pc) and 15 mg/day (315 mg pc). A total of 37 courses was administered. Toxicity was evaluated using NCI-CTC criteria. Granulocytopenia was the main hematologic toxicity. Other hematologic toxicities were sporadic. Non-hematologic toxicities were mild and consisted of grade 1 nausea and grade 2 alopecia. Pharmacokinetic analyses were performed in six patients each treated with 10 mg/day and 12.5 mg per day, and in one patient treated with 15 mg/day. Using a two-compartment model, t1/2 alpha ranged from 0.47 to 1.54 h and t1/2 beta from 2.0-11.6 h. Mean values for Cmax and AUC were 1.47 +/- 0.331 microgram/ml and 13.67 +/- 3.81 micrograms/ml.h. No objective tumor responses were observed. However, one patient with metastatic breast cancer had stable disease for twelve months. We conclude that the Maximum Tolerated Dose of NK611 administered daily for 21 consecutive days is 12.5 mg/day. The Dose-Limiting Toxicity is granulocytopenia. The recommended dose for further clinical Phase II studies is 10 mg/day.
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PMID:Clinical and pharmacokinetic phase I trial of oral dimethylaminoetoposide (NK611) administered for 21 days every 35 days. 915 73

Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.
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PMID:Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies. 917 29

The results in 9 patients with unresectable recurrent squamous cell cancer of the head and neck who were treated with aggressive concurrent chemoradiotherapy are reported. Treatment consisted of one or two courses of chemotherapy with 5-fluorouracil 1000 mg/m2/day and cisplatin 20 mg/m2/day, both given as 4-day continuous intravenous infusions, concurrent with radiation therapy. Salvage radiation doses between 30 and 70 Gy were administered. Seven patients had previously undergone an attempt at curative surgery, and 7 had been treated with radiation doses between 52 and 72 Gy. The recurrent disease was locally confined in 3, locoregional in 5, and locoregional with metastases in 1 of the 9 patients. Treatment toxicity was significant and included mucositis, nausea/vomiting, and granulocytopenia, but there were no toxic deaths. Complete tumor clearance was possible in 6 of these 9 patients, and 5 patients remain disease-free at 41+, 43+, 45+, 47+, and 50+ months. Of these 5 patients, 4 had previously been treated with both surgery and radiation, while 1 had only undergone surgery. We conclude that aggressive chemotherapy and concurrent (re)irradiation can be given to patients with unresectable, recurrent, squamous cell cancer of the head and neck. Treatment is tolerable, and disease-free long-term survival is possible. Careful patient selection, however, is required.
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PMID:Concurrent chemoradiotherapy for salvage in relapsed squamous cell head and neck cancer. 931 24

Forty five patients at the age of 15 to 84 years with signs of infection requiring active antibacterial therapy were treated with cefotetan. In the majority of the patients pulmonary affections such as double pneumonia, pleurisy or bronchopneumonia were stated. In some patients bronchopulmonary pathological processes were associated with pancreatitis, cholecystitis or other diseases of the gastrointestinal tract. A separate group included patients with diseases of the small pelvis organs (pelvioperitonitis, metroendometritis or prostatitis) and diseases of the urogenital system (pyelonephritis) arachnoiditis. In all the patients except for one with bronchopneumonia at the background of chronic myeloleukemia and agranulocytosis the results of the treatment were good and satisfactory. Cefotetan proved to be efficient in the treatment of purulent affections of the skin and subcutaneous fat (abscesses and phlegmona), trophic disturbances at the background of pathological processes in the vessels and pyoseptic condition. Cefotetan practically had no side effects. Only in 2 patients insignificant nausea during the first 2 days of the treatment was recorded. In some patients the antibiotic intramuscular injections were painful with formation of cold infiltrates. After intravenous administration of cefotetan no adverse reactions were observed.
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PMID:[Effectiveness of cefotetan in clinical practice]. 933 42

Desferrioxamine (DFX) remains the most effective and safe iron chelator for treatment of patients with transfusional iron overload. It is usually given by intermittent subcutaneous infusions for 8-12 h on 4-6 days weekly using a battery-driven pump. Disposable balloon infusers provide a suitable method of giving continuous subcutaneous infusions with improved patient compliance. For patients with cardiac abnormalities due to iron overload, continuous intravenous desferrioxamine is essential to eliminate toxic plasma non-transferrin bound iron and to reduce body iron stores. Deferiprone (L1, l-2 dimethyl-3hydroxy-pyrid-4-one) is a less effective iron chelator but has the advantage of being orally active. Long-term trials in which patients have taken 75 mg/kg/day have shown that deferiprone is capable of maintaining body iron stores at safe levels in a proportion of thalassaemia major patients but body iron stores, assessed by liver biopsy remain at high levels (> 15.0 mg/g dry weight) in a substantial number of patients. These concentrations have been associated with tissue damage. Trials of increased doses of deferiprone (up to 100 mg/kg/day) or of combined therapy with daily deferiprone and DFX or 1 or 2 days each week are being carried out in an attempt to achieve lower body iron burden in these patients. Preliminary results show that the drugs can be given safely together and urine iron excretion produced is additive, implying that the drugs chelate different body iron pools. Patients previously well chelated with serum ferritin levels less than 2500 micrograms/L have the fewest side-effects from deferiprone and usually may be kept at the same level of body iron for periods of at least 4 years, assessed by serum ferritin and urine iron excretion. The side-effects of deferiprone result in some patients discontinuing therapy. These side-effects, especially arthropathy, mainly occur in previously poorly chelated and so the most heavily iron-loaded patients. Nausea and other gastrointestinal symptoms, agranulocytosis or milder degrees of neutropenia account with arthropathy for nearly all the withdrawals from deferiprone therapy. Patients with cardiomyopathy due to iron overload should be given intravenous DFX rather than deferiprone. Deferiprone, licensed for pharmaceutical use in India, awaits official approval for widespread clinical use in Western Europe and North America. Meanwhile, attempts to find new orally active iron chelators and improved methods of administration of desferrioxamine are in progress.
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PMID:Iron chelation therapy. 935 Jan 80

Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes on a daily X 5 schedule, every three weeks, with a starting dose of 1.5 mg/m2. Twenty patients were entered onto the study, all of whom were eligible. All patients were evaluable for toxicities. Half of these patients experienced at least one Grade 4 hematologic toxicity, comprised of either granulocytopenia or leukopenia (4 patients with both, 3 patients with grade 4 granulocytopenia, and 2 patients with only grade 4 leukopenia). Other non-life threatening (Grade 3) toxicities included nausea (2 patients), weakness (2 patients), weight loss (1 patient), blurred vision (1 patient), diarrhea (1 patient) and malaise/fatigue/lethargy (1 patient). Two patients achieved a partial response, for an overall response rate of 10% (95% confidence interval of 1.2 to 31.7%). The median survival for the 20 patients was five months.
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PMID:Phase II trial of topotecan in advanced gastric cancer: a Southwest Oncology Group study. 938 50

A prospective phase II trial was carried out to define the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon alpha-2b (IFN-alpha) in combination with intravenous administration of vinblastine (VLB) in patients with metastatic renal cell cancer (RCC). Thirty-one patients with advanced RCC who had received no prior biochemotherapy were treated with IL-2 4.5 MU x 2/24 h thrice weekly for 2 weeks, IFN-alpha 3 MU/24 h thrice weekly (alternating days) for 2 consecutive weeks and VLB 4 mg/m2 every 3 weeks. Patients were to have a 1-week rest period after each 2 weeks of therapy with cytokines. Treatment was repeated every 3 weeks. Maximum duration of treatment was 1 year. Treatment was administered on an outpatient basis. There were 4 complete (12.9%) and 8 partial responses (25.8%), with an overall response rate of 38.7%. The median duration of response was 6.5 months. Responses were seen in lung, lymph nodes, bones, liver and other tumor metastases. Toxicity was mild to moderate, consisting of fever, anorexia, malaise and nausea-vomiting in > 80% of patients. Hypotension and transient alopecia occurred in > 20% of patients. Liver enzyme elevation was frequently observed. Treatment-induced eosinophilia occurred in the majority of patients, while in 52% of patients granulocytopenia grade II and grade III did not require dose modification of drugs. Transient inflammation and local induration at the injection sites was observed in the majority of patients. None of the patients experienced major VLB-related toxicity and no toxic deaths occurred. This three-drug combination immunochemotherapy may be a promising regimen with modest toxicity in advanced RCC.
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PMID:An outpatient phase II study of subcutaneous interleukin-2 and interferon-alpha-2b in combination with intravenous vinblastine in metastatic renal cell cancer. 942 69


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