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)

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

1-beta-D-Arabinofuranosylcytosine (ara-C), 2 or 3 g/sq m, was administered as a 1-hr i.v. infusion every 12 hr for 10 or 12 doses to patients with acute leukemia and refractory lymphoma. Four of seven patients with relapsed or refractory acute myelocytic leukemia and two of four patients with previously untreated acute myelocytic leukemia achieved complete remission. Of five treatment failures, two patients had leukemia which was clearly resistant to high-dose ara-C, and three patients died of infections or hemorrhagic complications during periods of pancytopenia. Three patients with acute myelocytic leukemia in remission received high-dose ara-C as consolidation therapy following previous courses of intensive, multiagent consolidation chemotherapy. Two of these three patients had prolonged thrombocytopenia following high-dose ara-C. Five patients with refractory acute lymphocytic leukemia were treated. Three patients achieved partial remission, and two patients had drug-resistant disease. Complete or partial disappearance of measurable disease parameters was seen in three of three patients with refractory lymphoma. Response was seen in five of five patients with meningeal leukemia, including complete response in one patient with extensive meningeal infiltration. Toxicity of this regimen was generally moderate and limited to pancytopenia and mild nausea. Patients who had received prior multiagent consolidation chemotherapy appeared to be at greater risk for hematopoietic toxicity. Patients who had received prior cranial irradiation or intrathecal chemotherapy appeared to be at greater risk for neurological toxicity. Plasma levels of ara-C immediately after completion of the infusion were 17.96 +/- 8.02 (S.D.) and 35.0 +/- 2.8 micrograms/ml for doses of 2 and 3 g/sq m, respectively. From 160 to 720 min following completion of the infusion, the plasma levels of drug were comparable to steady-state levels achieved with a continuous infusion of ara-C at 100 mg/sq m over 24 hr. A high degree of penetration into the central nervous system was demonstrated. High-dose ara-C has substantial activity against leukemic and lymphomatous cell populations, including cell populations resistant to conventional doses of the drug, and is an effective treatment modality for patients with these diseases. The high degree of penetration into the central nervous system suggests that this drug regimen may be useful as consolidation therapy for patients at high risk for central nervous system disease.
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PMID:A pilot study of high-dose 1-beta-D-arabinofuranosylcytosine for acute leukemia and refractory lymphoma: clinical response and pharmacology. 694 42

Twenty two patients with acute relapsed leukemia (AML 20, ALL 2) were treated with 5-aza-2'-deoxycytidine (DAC) and either m-amsacrine or idarubicin. DAC was administered as a 6-h infusion, every 12 h for 6 days in combination with either m-amsacrine (120 mg/m2) as a 1-h infusion on days 6 and 7 (n = 19) or idarubicin (12 mg/m2) as a 15-min infusion on days 5, 6 and 7 (n = 3). Thirteen patients (59%) achieved a complete remission. The treatment was complicated by nausea, vomiting, diarrhoea with signs of peritonitis (n = 9), weight loss (n = 7), cerebellar or cerebral toxicity (n = 2), gastrointestinal bleeding (n = 3), liver toxicity (n = 2) and prolonged myelosuppression. Median duration of remission was 4 months (range 1-30). The preliminary data show that DAC is an anti-leukemic agent, comparable to high dose Ara-C with comparable severe toxicity.
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PMID:Preliminary results with 5-aza-2'-deoxycytidine (DAC)-containing chemotherapy in patients with relapsed or refractory acute leukemia. The EORTC Leukemia Cooperative Group. 768 57

Thirty adult patients with relapsing or refractory acute leukemia were treated with mitoxantrone 10 mg/m2 daily by 20-min intravenous infusion for 5 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 5 days. Complete remission was obtained in 9 of 15 patients (60%) with acute myeloblastic leukemia (AML), with a mean duration of 6 months (range 2-12 months). Among 15 patients with acute lymphoblastic leukemia (ALL), complete remission was obtained in 5 patients (33.3%), with a mean duration of 2 months. Partial remission was achieved in 2 patients with AML and 1 patient with ALL. Myelosuppression developed in all patients following chemotherapy. Nonhematologic side effects consisted of nausea, vomiting, mild alopecia, stomatitis and transient hepatic dysfunction. No cardiopulmonary toxicity or neurotoxicity was observed. Our therapeutic responses are similar to those obtained with high-dose Ara-C and mitoxantrone but with less toxicity.
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PMID:Mitoxantrone and standard dose cytosine arabinoside therapy in refractory or relapsed acute leukemia. 798 76

A 77-year-old female with left hemiplegia caused by cerebral infarction and with mild senile dementia was admitted for further examination of hematological abnormalities. She was diagnosed as acute myelogenous leukemia (AML-M5a) according to French-American-British classification. Since intensive combination chemotherapy seemed difficult, she was treated with oral administration of cytarabine ocfosfate (200 mg/day, for 14 days), a cytidine deaminase-resistant derivative of Ara-C, resulting in complete remission. Major side effects were nausea, vomiting and appetite loss, but their incidences were reduced tolerably when cytarabine ocfosfate was given just before sleeping. Cytarabine ocfosfate might be useful to treat AML in elderly patients having certain complications such as cerebrovascular disease.
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PMID:[Successful treatment of acute myelogenous leukemia in an elderly patient with cytarabine ocfosfate]. 812 96

Five children with AML were treated with high-doses of Ara-C (2 g/m2) during consolidation. After 17 cycles the toxicity was evaluated. Granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 25 x 10(9)/l) were stated after 15/17 and 13/17 cycles respectively. The nadir of bone marrow suppression appeared between day 10 and 14. In one case treatment related death during severe myelosuppression was noted. In individual cases jaundice with elevated activity of aminotransferases, paralytic ileus and pulmonary oedema were observed. All these adverse reactions were reversible. Other toxicities such as nausea/vomiting, stomatitis, diarrhea, infections and drug related fever were transient. No neurologic toxicity was seen. There is a need for developing a new way of the administration of high-dose Ara-C which could substantially reduce toxicity of the drug.
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PMID:[Preliminary evaluation of adverse effects after administration of arabinoside cytosine (Ara-C) in high doses to children with acute myelogenous leukemia]. 820 12

Ninety-seven patients with refractory or relapsed acute myelogenous leukemia (AML), median age 37 years, received as salvage therapy a single course of idarubicin 6 mg/m2 as an intravenous (i.v.) bolus daily for 5 days, cytarabine (Ara-C) 600 mg/m2 i.v. for a period of 2 hours daily for 5 days and etoposide (VP-16) 150 mg/m2 for a period of 2 hours daily for 3 days (ICE protocol). Thirty-six patients were primarily resistant to standard inductive therapy with daunorubicin and Ara-C; 50 patients were in first relapse, three patients in second or third relapse, and eight patients in relapse after transplants. Forty-two (43%) out of 97 patients achieved complete remission, 11 patients died of infection or hemorrhage during induction, and 44 patients (45%) had resistant disease. Of the various variables examined, only disease status (i.e. refractory versus relapsed AML) was predictive for a significantly lower response rate. The median remission duration was 16 weeks; the overall median survival was 10 weeks. Nausea, vomiting, and oral mucositis were common but were rarely severe. No patient experienced treatment-related cardiac toxicity. In conclusion, the ICE protocol is a tolerable regimen providing effective antileukemic activity in patients with advanced AML. The evolution of this protocol in previously untreated patients with AML appears indicated.
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PMID:Idarubicin in combination with intermediate-dose cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The GIMEMA Cooperative Group. 842 73

Thirty patients with chronic myeloid leukemia in chronic phase and less than 1 year from diagnosis were treated with a combination of interferon alfa-2a (IFN) 9 million units daily continuously and intermittent low-dose cytosine arabinoside (Ara-C) 20 mg/m2 daily for 21 days every 42 days. The leukemia was controlled initially with hydroxyurea prior to commencing IFN and Ara-C. The treatment was continued for at least 12 months after which time nonresponders were withdrawn from the trial and responders continued on IFN alone. The median duration of follow-up is 14 months (range 10-53 months). Hematological response was assessed by clinical and laboratory parameters and cytogenetic response was assessed by regular bone marrow chromosome analysis. A complete hematological response occurred in 28/30 patients (93%). A complete cytogenetic response (no detectable Philadelphia chromosome-positive metaphases) was present on at least one occasion in 9/30 (30%), a partial cytogenetic response (between 1 and 34% Philadelphia chromosome-positive metaphases) in 7/30 (23%) and a minor response in 4/30 (13%), giving an overall cytogenetic response rate of 67%. Significant side effects included mucositis, nausea, cytopenia and depression. Side effects could be managed by dose reduction or temporary cessation and were tolerable in most patients, but in 1 patient this led to withdrawal from the trial due to severe depression. Two patients have transformed, 1 to acute lymphoblastic leukemia and 1 to accelerated phase. Two patients have died after exiting the study, both from complications of allogeneic bone marrow transplantation. In conclusion, these results are superior to the results using IFN alone and indicate the need for a randomized study.
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PMID:Combined interferon alfa-2a and cytosine arabinoside as first-line treatment for chronic myeloid leukemia. 847 67

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.
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PMID:Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. 869 37

This report describes the results of induction chemotherapy with idarubicin (IDA) plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a newly designed induction regimen, in cases of previously untreated acute myelogenous leukemia (AML). The study was conducted by the Multicenter Clinical Study Group of the Korean Biologic Response Modifier Society (KBRMS). From March 1994 through January 1995, 40 patients were treated. The median age was 30 years (range, 15 months to 65 years), with a distribution according to the French-American-British (FAB) classification of one MO, nine MI, 15 M2, six M3, four M4, and five M5 patients. Remission induction therapy consisted of IDA 12 mg/m2 intravenously (i.v.) over 30 minutes daily on days 1 to 3, in combination with BH-AC 300 mg/m2 over 4 hours daily on days 1 to 7 (in patients aged 41 to 65 years, BH-AC dosage was decreased to 200 mg/m2/d). Complete remission (CR) was achieved in 30 patients (75%), 22 by the first induction therapy and eight by the second induction therapy. Ten patients (25%) failed to respond to therapy, six due to resistant disease and four due to death caused by aplasia. The time to CR was 30 days, the median granulocytopenic period was 19 days, and the thrombocytopenic period was 24 days. All nonhematologic side effects such as nausea, vomiting, mucositis, skin eruption, liver and cardiac dysfunction, and neurotoxicity, were transient and tolerable. These data indicate an efficacy comparable to that of other combinations of IDA (or other anthracyclines) with cytosine arabinoside (Ara-C) for remission induction in AML.
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PMID:Induction chemotherapy with idarubicin plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine in acute myelogenous leukemia: a newly designed induction regimen--a prospective, cooperative multicenter study. 891 13


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