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)

Thirty two patients with refractory or recurrent acute leukemia or blast crisis of chronic myelocytic leukemia were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C), 100 mg/m2 [group I (n = 15)] or 200 mg/m2 [group II (n = 18)], and tetrahydrouridine (THU) 350 mg/m2, given concurrently as a 3 h continuous intravenous infusion at 12 h interval for eight doses. Two of 13 (15.3%) evaluable patients in group I achieved a complete response, both of whom had acute myelocytic leukemia. In group II, seven of 14 evaluable patients (50%) obtained objective responses--six with complete responses (42.8%) and one with partial response (7%). Myelosuppression was seen in all patients with a median duration of 32.5 days (group I) and 36.3 days (group II), respectively. Non-hematologic toxicity consisted of nausea, vomiting, diarrhea, conjunctivitis, skin rash, hepatocellular toxicity, hemorrhage, and renal toxicity. Pharmacokinetic studies revealed, for group I, mean peak plasma Ara-C levels at 3 h (Cp3h) of 1254 ng/ml, area under the curve (AUC) 4651 ng x h/ml, total body clearance (TBC) 32.65 l/h/m2, renal clearance (RC) 7.04 l/h/m2 with a mean of 12.36% of the injected amount of Ara-C excreted unchanged in urine over the first 24 h. The corresponding mean values for group II are Cp3h 3305 ng/ml, AUC 15080 ng x h/ml, TBC 20.48 l/h/m2, RC 7.02 l/h/m2 and 26.23%. Ara-C 200 mg/m2 combined with THU gave serum Ara-C levels and response rates comparable to those achieved with high dose Ara-C (HiDAC) (greater than or equal to 1 g/m2). Central nervous system toxicity associated with HiDAC was not seen. Pharmacokinetics for uracil arabinoside (Ara-U) in patients treated with Ara-C 200 mg/m2 plus THU, were comparable to values seen with Ara-C for Cp3h, AUC and 24 h urine, amounting to 3160 ng/ml, 21717 ng x h/ml and 23.62% whereas TBC was significantly lower (p less than 0.001) for Ara-U than for Ara-C (3.02 versus 20.48 l/h/m2).
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PMID:Therapy of refractory/relapsed acute leukemia with cytosine arabinoside plus tetrahydrouridine (an inhibitor of cytidine deaminase)--a pilot study. 196 Oct 42

We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.
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PMID:4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D-arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia. 291 Apr 65

Sixteen patients with previously treated acute nonlymphocytic leukemia or chronic myelogenous leukemia in blast crisis were given one to three courses of esorubicin by continuous infusion over 48 h. Dosage levels extended from 35 to 85 mg/m2. Four patients showed partial responses of short duration. Nonhematological toxicity observed at dosages of 55 to 85 mg/m2 were mucositis, diarrhea, skin rash, transaminitis, nausea, vomiting, and cardiac dysfunction. One patient receiving 85 mg/m2 developed acute florid congestive heart failure within hours of administration of the drug. Pharmacokinetic analysis revealed large interpatient variation in plasma drug levels. At the end of infusion, plasma decay of esorubicin was rapid initially but slow thereafter, with a terminal half-life of 20 to 54 h. The metabolite 4'-deoxy-13-hydroxydoxorubicin reached significant plasma levels. Total body clearance, renal clearance, volume of distribution at steady state, and mean residence time show little variation during dose escalation for both esorubicin and 4'-deoxy-13-hydroxydoxorubicin. Urinary excretion of esorubicin and 4'-deoxy-13-hydroxydoxorubicin accounted for 10.5 and 1.5%, respectively, of the administered dose.
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PMID:Pharmacokinetic and phase I evaluation of esorubicin (4'-deoxydoxorubicin) by continuous infusion over forty-eight hours in patients with leukemia. 316

Sixteen children with refractory hematological malignancies were treated with a combination of BH.AC, aclacinomycin-A, 6-MP and predonisolone (BH-AC.AMP protocol). They were ALL(6), ANLL(8), CML(1) and NHL(1). The CR ratio was 17% in ALL, 50% in ANLL, and blast crisis of CML was treated successfully but NHL failed in the induction remission. Major complications were vomiting, nausea, gastrointestinal bleeding, hematuria and hemorrhagic cystitis. More than 10 days or 120 mg/m2 administration of aclacinomycin-A was thought to induce more severe side effects.
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PMID:[BH-AC.AMP protocol in the treatment of refractory childhood acute leukemia]. 317 40

A phase II clinical trial on MDS was conducted in a cooperative study with orally administrable ara-C analogue, PLAC, which is resistant to cytidine deaminase and had shown an anti-tumor activity on various experimental tumors by oral route. Fifty MDS (3 RA, 18 RAEB, 11 RAEB-T, 18 RAEB-blast crisis (BC) were treated orally with 100 to 400mg/body of daily PLAC. One good response (GR) and 3 partial responses (PR) were obtained in 18 RAEB, and 2 complete remissions, 1 GR and 1 PR were noted in 11 RAEB-T, while 3 PR were seen in 18 RAEB-BC. Overall CR rates were 4%, GR rates 4% and PR rates 14%. Thus, 22% of MDS responded to oral PLAC. No clear daily dose-response was noted. Response, however, was dependent on the treatment period and was obtained in cases which had been treated for more than 20 days. Besides myelosuppression, side effects were mainly gastrointestinal, and anorexia (32%), nausea/vomiting (30%) and diarrhea (8%) were observed. Oral PLAC seems to be active on MDS which does not necessarily require admission to hospital.
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PMID:[Treatment of myelodysplastic syndromes (MDS) with oral administration of N4-palmitoyl-1-beta-D-arabinofuranosyl cytosine (PLAC)]. 338 95

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.
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PMID:A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia. 354 13

A phase II study of the oral agent methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU tablet) for myeloproliferative disorders was performed. Fifty-two patients were treated with MCNU tablets and 43 patients were evaluated for clinical effects and 45 for adverse effects. The standard regimen was as follows; oral administration of 50mg (one tablet)/body/day every 4-6 days was considered as one course, and this was repeated at 6-8-week intervals if possible, with certain modifications according to dosage, period of administration and dose interval wherever necessary. Of 16 patients with chronic myelogenous leukemia (CML) in the chronic phase, 13 achieved complete remission (CR), and 3 achieved partial remission (PR). The overall response ratio was 100%. Rapid reduction of leucocytes was detected within two weeks. One patient with CML in blast crisis achieved PR (100%). Of 15 patients with polycythemia vera, 13 showed an excellent effect (87%), and 1 a moderate effect (6.7%), the overall response ratio being 93%. In essential thrombocythemia, an excellent effect (70%) was obtained in 7 of 10 patients. One patient with myelofibrosis showed an excellent effect (100%). Nausea & vomiting (33%) and anorexia (13%) were major adverse effects, but these symptoms were observed only transiently. Liver dysfunction was also seen in 8.9% of patients, but no patient showed severe manifestations. Our study supports the contention that MCNU tablet is a useful agent against myeloproliferative disorders.
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PMID:[Phase II study of a new nitrosourea derivative, MCNU, in tablet form. Takai Blood Cancer Study Group]. 356 4

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

The safety, tolerance, and clinical effects of combined therapy with recombinant interferon-alpha (IFN-alpha) and interleukin-2 (rIL-2) administered subcutaneously for 2 courses of 4 weeks each, with 4 weeks interval between courses, given as outpatient therapy have been assessed in 10 patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML). All patients were previously treated with conventional chemotherapy and 3 failed to respond to IFN-alpha administered prior to our study. Median duration of disease from diagnosis was 36 months. Seven patients were in first chronic phase and the other 3 were in blast crisis, second chronic phase, and relapse post-bone marrow transplantation (BMT), respectively. Hematological response (median follow-up 16 months) was observed in 9 patients, with a decline in number of white blood cells and platelets. Elimination of Ph1 was observed in the patient who relapsed post-BMT with complete elimination bcr/abl RNA by polymerase chain reaction. Rebound lymphocytosis and eosinophilia were observed in most of the patients. Toxicity was acceptable. The main adverse effects were fever, chills, fatigue, anorexia, nausea, and vomiting. The side effects were reversible and no interruption of treatment was required. There was no treatment-related hospitalization or deaths. These data suggest that simultaneous subcutaneous IFN-alpha and rIL-2 home therapy is feasible, reasonably well tolerated, and potentially beneficial in CML patients. These observations may have important implications for the treatment of minimal residual disease following allogeneic and autologous marrow transplantation.
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PMID:Treatment of chronic myelogenous leukemia with recombinant human interleukin-2 and interferon-alpha 2a. 792 12

Six patients with either acceleration or blast crisis of transformed chronic myeloid leukemia (CML) were treated with high-dose interferon alpha in combination with hydroxyurea. All patients responded to the treatment by reversal to stable chronic phase. Two of these patients responded repeatedly during their course of disease. Median time for return to chronic phase was 4 weeks. Adverse side-effects such as nausea, vomiting, hairloss, fever, prolonged cytopenia were not observed.
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PMID:Successful treatment of accelerated and blastic phase of chronic myeloid leukemia with high-dose interferon alpha and hydroxyurea: a novel approach. 857 62


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