Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacology, chemistry, pharmacokinetics, clinical studies, and adverse effects of amsacrine, an investigational antineoplastic agent, are reviewed. Amsacrine's mechanism of action is not clearly understood, although the drug is known to inhibit DNA synthesis. As an investigational NCI "Group C" agent, amsacrine is available to physicians for the treatment of adult patients with refractory acute nonlymphocytic leukemia (ANLL) under an established protocol. Following intravenous administration, amsacrine has a biphasic plasma clearance. It is extensively metabolized by the liver to inactive compounds that are excreted in the bile. Phase I studies indicated that amsacrine was potentially effective in patients with solid tumors and acute leukemias. Patients with solid tumors could tolerate much lower doses of amsacrine than leukemia patients because of dose-limiting bone-marrow suppression in the former. In Phase II studies, amsacrine appeared effective in treating the acute leukemias, with response rates of 31% and 23% for acute lymphocytic leukemia and ANLL, respectively. Patients with other types of cancers have not responded to amsacrine therapy. Frequently occurring adverse effects of amsacrine include leukopenia and thrombocytopenia in patients with solid tumors; nausea, vomiting, and diarrhea; mucositis in patients receiving higher doses (leukemia patients); alopecia; hepatotoxicity; and phlebitis. The clinical usefulness of amsacrine appears limited to treatment of the acute leukemias. Studies of combination therapies that include amsacrine are currently underway and should further define the therapeutic role of amsacrine.
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PMID:Review of amsacrine, an investigational antineoplastic agent. 676 91

High-dose cytarabine (HDARA-C) at doses ranging from 1000 to 3000 mg/m2 administered as 30-min iv infusions was used in 12 patients with acute leukemia. HDARA-C toxicity was marked by nausea, vomiting, and somnolence; fever occurred in one patient. Myelosuppression was brief and reversible; the wbc count nadir occurred between Days 10 and 15 after treatment. In this study of a limited number of patients, no reliable conclusions could be drawn about antileukemic activity. However, (a) HDARA-C appeared to be a well-tolerated regimen in acute myeloblastic leukemia in complete remission; (b) a clear improvement was obtained in a patient with central nervous system leukemia; and (c) a sharp but transient decrease in peripheral blast cell counts was seen in two patients with acute myeloblastic leukemia. Cytarabine distribution was bi- or tri-compartmental; plasma final half-life was greater than 4 hrs in six patients. Pharmacokinetic parameters were not correlated with serum deoxycytidine deaminase activity. HDARA-C crosses the blood-brain barrier and may be useful in the prophylaxis against and treatment of central nervous system leukemia.
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PMID:High-dose cytarabine in acute leukemia: toxicity and pharmacokinetics. 685 Jun 54

The analgesic agent butorphanol was evaluated for its ability to block cisplatin-induced emesis in ferrets and dogs. In ferrets, butorphanol (0.15, 0.3, or 0.45 mg/kg; expressed in terms of the tartrate salt) administered sc 30 minutes prior to cisplatin (8 mg/kg iv) reduced the number of emetic episodes but did not eliminate them. When these doses of butorphanol were administered 30 minutes before and 30 and 90 minutes after cisplatin, they caused a dose-related reduction in the number of emetic episodes; there was complete protection at a dose of 0.45 mg/kg/injection. In dogs, butorphanol (0.185 or 0.37 mg/kg/injection, expressed in terms of the tartrate salt) was administered sc on the same multiple-dose schedule used in the ferrets; this caused a nearly complete elimination of the emetic response to cisplatin (3 mg/kg iv). Butorphanol caused some sedation in both species at effective antiemetic doses but had no effect on the antitumor activity of cisplatin against murine L1210 leukemia. Naloxone blocked the antiemetic effect of butorphanol in ferrets, indicating the involvement of opiate receptors. The results of these studies suggest that butorphanol may be useful clinically in mitigating the emetic effects of cisplatin.
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PMID:Antiemetic activity of butorphanol against cisplatin-induced emesis in ferrets and dogs. 688 14

m-AMSA is a synthetic aminoacridine DNA intercalator found to have experimental murine antitumor activity. A phase I investigation was undertaken in 71 patients with solid tumors and acute leukemia. Using an intermittent every 3-week schedule in solid tumors, toxicity encountered was primarily hematologic, predominantly leukopenia with relative platelet sparing. The recommended dose for phase II evaluation in patients with solid tumors is 90 mg/m2 every 3 weeks; patients with minimal prior therapy could be treated at 120 mg/m2 and patients with hepatic dysfunction or marginal bone marrow reserve should have an initial dose reduction to 70 mg/m2. Therapeutic activity was seen in Hodgkin's disease, hepatoma, and epidermoid carcinoma of the esophagus. Various dose schedules were studied in leukemia. The recommended dose for phase II evaluation is 120 mg/m2 daily for 5 days as a daily 30-minute infusion. At this dose, nausea, vomiting, mucositis, alopecia, and hepatic toxicity were noted. Therapeutic activity was seen in AML, blastic CML, and CLL. Further clinical trials with this agent are warranted.
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PMID:Phase I study of m-AMSA in patients with solid tumors and leukemias. 689 83

Forty-six patients with inoperable cancer and leukemia in relapse were given vindesine (VDS) either by iv bolus weekly at doses ranging from 2.0 to 5.5 mg/m2 or by 24-hour continuous infusion weekly at doses ranging from 1.0 to 7.0 mg/m2 of estimated body surface area. VDS was well-tolerated by patients with normal liver function who had previously been minimally treated with myelosuppressive agents at a dose of less than or equal to 4 mg/m2 either by iv bolus or by 24-hour infusion weekly. The dose-limiting toxic effects of VDS were leukopenia and neurotoxicity. Leukopenia was cumulative but easily reversible by interruption of weekly dose. Neurotoxicity was insidious and hardly reversible. Patients with liver dysfunction appeared to develop more neurotoxicity. Other toxic effects included a decrease in hemoglobin level, transient hepatic dysfunction, cellulitis or phlebitis at the iv site, stomatitis, nausea, and vomiting. Degrees and parameters of toxic effects observed after iv bolus and 24-hour infusion of the same doses were indistinguishable except for an increased incidence of local cellulitis in the infusion group.
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PMID:Initial clinical study with vindesine: tolerance to weekly iv bolus and 24-hour infusion. 692 28

17 patients (age 15-58 years) with refractory acute leukaemia (14 AML, 3 ALL) were treated with high dose cytosine arabinoside (AraC) at a dose of 3000 mg/m2, twice daily for 6 d (13 patients with AraC alone, 4 patients with AraC and doxorubicin). 9 patients achieved complete remission (53%) and 2 a partial remission. Although sophisticated isolation and blood banking facilities are required during the pancytopenic period, the toxicity of this treatment was acceptable. Vomiting, headache, somnolence, fever, conjunctivitis and cardiac arrhythmias were found most frequently. The unexpected pulmonary failure in 3 patients was worrisome. The duration of remissions was from 1 to 12 months. Results obtained with high dose AraC are satisfactory and hold promise for the treatment of patients with previously untreated AML.
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PMID:High dose cytosine arabinoside in the management of refractory acute leukaemia. 695 4

A 4-year-old girl presenting with vomiting, abdominal pain, and renal failure was found to have gross hepatosplenomegaly, a renal mass, and bilateral pleural effusions. A diagnosis of acute lymphoblastic leukaemia (ALL) was suggested by a peripheral white cell count (WCC) of 119,000 x 10(6)mm3, 57% blasts, 22% lymphocytes, and confirmed by bone marrow examination. Lymphocyte surface marker studies at diagnosis enabled classification as a T-ALL, with a significant proportion of the T cells also bearing receptors for the third component of complement (C3). Seventy-two percent of the peripheral blood mononuclear cells reacted with anti-Ia monoclonal antibody (FMC44), and a smaller proportion (25%) carried receptors for the Fc portion of IgG. The T-classification of this ALL was verified at central nervous system (CNS) relapse and at a subsequent nodal relapse. Double-marker studies on cells from the infiltrated lymph node prepared in suspension confirmed the presence of Ia-positive T cells. The Ia marker is usually a useful discriminant between T and non-T cells in normal and ALL cell populations. The case described here highlights the need for a panel of markers to be used in classification of childhood ALL and supports the suggestion that there is a distinct subtype of Ia-positive T-ALL.
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PMID:Childhood T-cell acute lymphoblastic leukaemia expressing "Ia-like" antigen:" a case report. 698 Oct 53

Twenty-two adult patients with relapsed leukemia were given aziridinylbenzoquinone (AZQ) intravenously in a phase I clinical trial. AZQ was administered as a 30-minute infusion daily for 17 days. Courses were repeated when the bone marrow returned to normal cellularity and full recovery from nonhematologic toxicity had occurred. The initial dose of AZQ was 8 mg/m2/d x 7. The highest dose given was 28 mg/m2/d x 7. A maximum of three patients were treated at each dose level and patients received at least two courses at a given dose level before they were eligible to be escalated to the next higher available AZQ dose level. Nonhematologic side effects were mild and included nausea/vomiting (32%), mucositis (18%), and alopecia (0%). Dose-limiting toxicity was bone marrow aplasia at the 28 mg/m2/d x 7 level. No complete or partial responses were observed in this initial study. For phase II adult leukemia studies using this schedule, it is recommended that the AZQ dose should be 24 mg/m2/d.
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PMID:A phase I trial of aziridinylbenzoquinone (NSC 192986) in patients with previously treated acute leukemia. 711 63

Rubidazone was administered to 24 children with advanced solid tumors or leukemia. The dose ranged from 80 to 150 mg/m2/IV daily to a total dose of 160 to 450 mg/m2/course. This course was repeated at intervals of approximately three weeks. Eighteen of 24 patients (75%) had received adriamycin and daunomycin as part of prior chemotherapy. The major toxic effects observed were myelosuppression, nausea, vomiting, mucositis, and skin rash. Four patients developed abnormal echocardiograms following the rubidazone therapy, 2 manifested clinical cardiac failure, of which one had anthracycline cardiomyopathic changes on autopsy. One of 7 adequately treated ALL patients achieved M2 marrow and improved peripheral counts for 3 weeks. One of the 2 neuroblastoma patients had subjective improvement of bone pain for 2 months. Rubidazone, in a previous heavily treated group of patients used in this study, had dosages of 360 and 450 mg/m2 which produced marrow hyperplasia to aplasia, with only minimal responses.
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PMID:Phase I trial of rubidazone (NSC 164011) in children with cancer. 726 27

2,3-Dihydro-1H-imidazo[1,2-b]pyrazole (IMPY) is an inhibitor of ribonucleotide reductase and of DNA synthesis selected for clinical trials because of its activity against L1210 leukemia variants resistant to other inhibitors of this enzyme. A phase I trial designated to allow in-depth pharmacologic evaluation has recently been completed and the clinical results and preliminary pharmacokinetic data are reported here. Each patient received IMPY by three different schedules. A single iv bolus, intermittent 5-day bolus, and 5-day continuous infusion were given at 3-week intervals. The major dose-limiting toxic effects were vomiting, rbc hemolysis, confusion, and somnolence. All toxic effects seemed to be dose- and schedule-dependent and were readily reversible. IMPY enters the cerebrospinal fluid and is highly concentrated in gastric secretions. Clearance of IMPY is impaired in the presence of hepatic insufficiency. Eighteen of 26 patients entered are evaluable for response, including one patient with colon cancer with minimal response and three patients with stable disease.
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PMID:Clinical toxic effects of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole (IMPY) with relevant pharmacokinetic parameters. 740 59


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