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)

Aziridinylbenzoquinone is a quinone compound capable of penetrating the central nervous system. It has demonstrated activity against both intracranial and i.p. murine tumors and human tumor xenographs. We have conducted a Phase I trial of aziridinylbenzoquinone in 60 children with advanced cancer who were refractory to conventional therapy. The drug was given by slow i.v. push on a daily schedule for 5 days every 3 to 4 weeks. The dose range explored included 6 dose levels, ranging from 6 to 12 mg/sq m daily for 5 days in patients with solid tumors and leukemia, and in patients with leukemia, 20, 25, and 30 mg/sq m daily for 5 days. Myelosuppression was the dose-limiting side effect. In patients with solid tumor the highest dose studied was 12 mg/sq m, and the median nadir white blood cell and platelet counts were 0.7 X 10(3) and 6.0 X 10(3)/microliter on Days 17 and 22, respectively. The median recovery day for white blood cells was 39. There may be some evidence of cumulative toxicity with prolonged thrombocytopenia. Other side effects were mild nausea, vomiting, and mucositis. Elevations in liver enzymes and bilirubin were transient and dose dependent, occurring 3 to 4 weeks after drug administration. Of the 34 children with solid tumors, 33 were evaluable for hematopoietic toxicity, 3 were early deaths, and 31 receiving a total of 55 courses were evaluable for therapeutic response. Partial responses lasting 3 weeks to 6 months were seen in the 4 patients with Hodgkin's disease, and in a child with a metastatic spinal cord ependymoma. Fifty-two courses were given to 9 patients with acute lymphocytic leukemia and 17 with acute nonlymphoblastic leukemia. Of the 15 patients with acute nonlymphoblastic leukemia treated at doses greater than or equal to 25 mg/sq m/day for 5 days there was one early death and there were 2 M1 (less than or equal to 5% blasts with normal cellularity), 3 M2A (6 to 15% blasts), and 2 M2B (16 to 39% blasts) bone marrow responses lasting 1 to 3.5 months. Aziridinylbenzoquinone demonstrated activity against acute nonlymphocytic leukemia with maximal tolerated doses of 30 mg/sq m daily for 5 days. Its effect in Hodgkin's disease is encouraging; however, further study will be required to determine its efficacy in central nervous system cancers. Recommended doses for Phase II studies, using daily schedule for 5 days in children with solid tumors, is 9 mg/sq m, and in children with leukemia, it is 25 mg/sq m.
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PMID:Phase I study of aziridinylbenzoquinone (AZQ, NSC 182986) in children with cancer. 669 81

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

Relapses in nine patients with acute myelocytic leukemia were treated with a combination of aclarubicin (ACR) and cytosine arabinoside (ara-C). ACR, 40 mg/m2/day, was administered daily by intravenous injection from day 1 to day 3 and ara-C, 60-80 mg/m2/day, divided into 2 doses, was given every 12 h by intravenous infusion from day 1 to day 7. Depending on the state of the bone marrow, ACR-ara-C regimen was modified in administration period and repeated after the resting periods of at least 7 days. Complete remission was obtained in 7 of 9 patients (77.8%). The time required for achieving the complete remission varied from 20 to 55 days with a median of 39 days. The duration of complete remission was from 8 to 52 weeks with a median of 22 weeks. Side effects on digestive system such as nausea, vomiting and anorexia, were seen in all patients, although they were managed by symptomatic treatment. The results indicate the effectiveness of this ACR-ara-C regimen in the clinical management of acute nonlymphocytic leukemia.
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PMID:Treatment of relapsed acute myelocytic leukemia with a combination of aclarubicin and cytosine arabinoside. 695 Jun 58

Cyclic administration of methotrexate (MTX) and L-Asparaginase (L-Asp) was utilized either as induction and maintenance chemotherapy or as maintenance chemotherapy alone following induction with other medications in treating 36 children with multiple relapses of acute leukemia. A complete remission rate (CR) of 67% was obtained in children with null-cell acute lymphocytic leukemia (ALL). The average length of remission was greater than four months. One of three patients with T-cell ALL and one of two patients with B-cell ALL achieved CR. In six cases of acute nonlymphocytic leukemia (ANLL), two patients achieved CR. One of two patients with terminal deoxynucleotidyl transferase (TdT) negative myeloblastic transformation of Ph'-positive chronic myelogenous leukemia (CML) obtained a CR lasting 20 weeks. Toxicity secondary to the chemotherapy included bone marrow suppression, hepatic injury, nausea, diarrhea, stomatitis, and allergic reactions to L-Asp. One case of subacute necrotizing leukoencephalopathy was seen.
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PMID:Methotrexate/L-asparaginase combination chemotherapy for patients with acute leukemia in relapse: a study of 36 children. 696 21

Indicine N-oxide, the first pyrrolizidine alkaloid N-oxide to be studied in the treatment of cancer in humans, was administered to ten patients: four children and two adolescents with refractory acute lymphocytic leukemia and four adults with refractory acute nonlymphocytic leukemia (three acute myelocytic, one myelomonocytic). Two patients, a 4-year-old boy with acute lymphocytic leukemia and a 22-year-old man with acute myelocytic leukemia, achieved complete remission lasting 3 and 5+ months, respectively. Another 15-year-old male with acute lymphocytic leukemia had a partial remission for four months. Toxicities included bone marrow suppression, mild anorexia and nausea, and transient elevation of liver enzymes. Jaundice and liver failure, presumably induced by drug, occurred in two patients.
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PMID:Activity of indicine N-oxide in refractory acute leukemia. 701 59

The treatment of refractory acute nonlymphocytic leukemia remains a major clinical problem in leukemia therapy. VP 16-213 is an investigational agent that may have specificity for monocytic blasts, and the combination of VP 16-213 and cyclophosphamide is synergistic in experimental leukemia. Seven patients with highly refractory acute nonlymphocytic leukemia, which demonstrated monocytic features, were treated with a combination of VP 16-213 and cyclophosphamide after they had failed to respond to multiple courses of intensive induction regimens. Three complete remissions and one partial remission were achieved. The times to complete remission were 21, 23, and 34 days. The durations of complete remission were 5, 9, and 12+ months. Myelosuppression was the most common side effect; one patient experienced nausea and stomatitis. There were no documented infections or hemorrhage, and no one died as a result of therapy. This combination is both well tolerated and effective in the treatment of refractory leukemia with monocytic features.
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PMID:VP 16-213 and cyclophosphamide in the treatment of refractory acute nonlymphocytic leukemia with monocytic features. 701 68

A phase I trial of diglycoaldehyde (Inox) in children with leukemia established that the maximum tolerated dose of a 5-day schedule was 1.5 g/m2/day. A phase II study was undertaken by the Children's Cancer Study Group to evaluate the efficacy of this dose. Forty-seven children with acute leukemia refractory to conventional forms of therapy were entered in the study: 29 patients with acute lymphocyte leukemia/acute undifferentiated leukemia and 18 with acute nonlymphocytic leukemia. Inox was administered at a dose of 1.5 g/m2 as a 4-6 hour iv infusion daily for 5 days every 14 days. Toxic effects included myelosuppression, proteinuria, nausea, vomiting, diarrhea, local tissue reactions, hypocalcemia, transitory serum amylase elevation, and transitory hypotension. There was one life-threatening episode of drug-related renal toxicity. Of the 27 patients who received a minimum of two courses, partial remissions were observed in two patients with acute nonlymphocytic leukemia. Inox was inactive against advanced acute lymphocytic leukemia.
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PMID:Phase II evaluation of diglycoaldehyde (Inox) in children with acute leukemia: a children's cancer study group report. 742 52

In an effort to determine if cell cycle active agents are augmented when given after non-cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone. Patients whose bone marrow did not show significant cytoreduction received 5-azacytidine. Twenty-seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission. A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5-azacytidine. Relapsed patients had a higher CR rate (36%) than refractory patients (15%). Nausea, vomiting, and stomatitis were common but rarely severe. The median duration of remission was 3.7 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes. In this patient population, there was no evidence that 5-azacytidine given after mitoxantrone increased the complete remission rate.
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PMID:Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study. 769 May 19

At concentrations >0.1 mM, hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU (1200 mg/m2) was followed 2 hours later by ara-C (250-3100 mg/m2) intravenously in 15 minutes. The combination was given on days 1, 2, 3 and 8, 9, 10. Thirty-three children [26 acute lymphocytic leukemia (ALL), 7 acute nonlymphocytic leukemia] were treated; 29 received at least 1 full course. All patients developed grade 4 cytopenias. Other grade 3 to 4 toxicities included hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9), and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5 ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1 to 3 mo). Twenty of twenty-six patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range: 0.21 to 0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism.
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PMID:Sequential oral hydroxyurea and intravenous cytosine arabinoside in refractory childhood acute leukemia: a pediatric oncology group phase 1 study. 1845 68


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