Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.
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PMID:Treatment of acute leukemia in relapse with 4'(9-acridinylamino) methanesulfon-m-anisidide (AMSA) in combination with cytosine arabinoside and thioguanine. 689 90

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

Patients with acute leukemia in relapse were given 5'-(9-acridinylamino)methanesulfon-m-anisidide at a dosage of 75 to 200 mg/sq m as a daily bolus infusion of 5 consecutive days. None of the 11 patients treated at 75 to 150 mg/sq m daily for 5 days achieved remission. Ten patients with acute lymphoblastic leukemia and 21 with acute nonlymphoblastic leukemia were given treatment at 200 mg/sq m daily for 5 days. Six of these patients achieved complete remission, three with acute lymphoblastic leukemia and three with acute nonlymphoblastic leukemia. Neutropenia and thrombocytopenia were seen in all patients and in the responders lasted a median of 39 and 41 days, respectively. Stomatitis was the most significant nonhematopoietic toxicity noted. occurring in 80% of the patients. Hyperbilirubinemia was seen in 25% of the patients treated. Since 4'-(9-acridinylamino)methanesulfon-m-anisidide will induce remission in heavily pretreated patients with acute leukemia, consideration should be given to exploring its use in combination with other active drugs.
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PMID:Phase I and II trial of 4'-(9-acridinylamino)methanesulfon-m-anisidide in patients with acute leukemia. 693 2

Thirty-two patients with relapsed or resistant acute leukaemia were treated with m-AMSA at doses ranging from 50-150 mg/m2 daily for 5 days. Complete remission was achieved in three of 18 patients with acute myeloblastic leukaemia, two of nine patients with acute lymphoblastic leukaemia, and none of five patients with blastic crisis of chronic myeloid leukaemia. The complete remissions all occurred at doses of 100 mg/m2 per day or above. Haematological toxicity occurred in all patients and was dose-related. Nausea and vomiting were mild and easily controlled. Alopecia was uncommon at the lower doses but occurred in all patients receiving the higher doses. Stomatitis was noted in only 8% of courses at 50 mg/m2 but was seen in 50% of courses at 150 mg/m2. Mild and transient elevations of liver enzymes were common. m-AMSA is an active drug in acute leukaemia, with acceptable toxicity. Its place in combination chemotherapy is now being explored.
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PMID:A phase I and II study of m-AMSA in acute leukaemia. 694 78

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

Forty-five patients with various forms of acute leukemia refractory to usual methods of treatment were treated with AMSA at doses of 100-200 mg/m2 iv daily for 5-7 days, for total doses of 500-1000 mg/m2/course. Among 41 evaluable patients, six (15%) achieved complete remissions, including two of 19 patients with typical acute nonlymphocytic leukemia, none of four with atypical acute nonlymphocytic leukemia, two of nine with chronic granulocytic leukemia in blast crisis, two of eight with acute lymphoblastic leukemia, and none of one with acute undifferentiated leukemia. Durations of complete remissions were 6, 7, 8, 12, 13, and 14 weeks. Four of the patients who died with infection during marrow hypoplasia 2-5 weeks after receiving AMSA had no evidence of leukemia on premortem bone marrow aspirates or postmortem examination. The primary toxic effects of AMSA were severe myelosuppression, stomatitis, and alopecia. One incident of life-threatening liver failure occurred. AMSA appears to be a promising agent for use in heavily pretreated patients with acute leukemia and chronic granulocytic leukemia in blast crisis.
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PMID:AMSA--a promising new agent in refractory acute leukemia. 704 28

A pilot study was carried out among 21 patients with advanced solid tumors to establish appropriate dose levels of PALA and 5-FU given on a 5-day schedule to produce definite but tolerable clinical toxicity. While dermatitis, diarrhea, leukopenia, and thrombocytopenia were observed, stomatitis was the dose-limiting side effect. The recommended initial dose levels for further clinical trials are 625 mg/m2 of PALA daily x 5 and 250-300 mg/m2 of 5-FU daily x 5, with courses repeated at 4-week intervals. Studies were also conducted to establish the time course of anticipated increased incorporation of 5-FU into cellular RNA following treatment with PALA. In murine P388 leukemia, PALA increased tritiated 5-FU incorporation by as much as 70%, the effect being maximal within 1 hour and maintained up to 25 hours. It was not possible to demonstrate increased tritiated 5-FU uptake into normal human leukocyte RNA from patients receiving combination chemotherapy with PALA and 5-FU, perhaps because of low rates of RNA synthesis.
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PMID:Pilot study of PALA and 5-FU in patients with advanced cancer. 705 70

The fusion toxin DAB389IL-2 is composed of the catalytic (C) and transmembrane (T) domains of native diphtheria toxin to which human interleukin-2 (IL-2) has been genetically fused (1,2). Following binding to the IL-2 receptor, the fusion toxin is internalized by receptor mediated endocytosis, and upon acidification of the endocytic vesicle, the T domain spontaneously inserts into the membrane, and facilitates the delivery of the C domain to the cytosol (3,4). In order to further study the process by which the C domain is delivered to the target cell cytosol, we genetically fused an eleven amino acid epitope derived from the vesicular stomatitis virus (VSV) G protein to the N-terminal end of DAB389IL-2. The epitope labelled fusion toxin, VSV-G-DAB389IL-2, was found to retain IL-2 receptor specific binding and cytotoxic activity. Target cells were incubated for various times in the presence of VSV-G-DAB389, fixed and then treated with anti-VSV G and FITC conjugated secondary antibody. Laser scanning confocal microscopy was used to determine the location of the fluorescent signal. The VSV-G epitope tagged fusion toxin was found only to be associated with small vesicles that were situated adjacent to the plasma membrane. These results suggest that the C domain of the fusion toxin is associated with an early intracellular compartment and is rapidly delivered to the cytosol. Since channel formation by the T domain is necessary for the delivery of the C domain, it follows that T domain insertion into the membrane also occurs early in the intoxication pathway.
Leukemia 1994 Apr
PMID:Epitope tagging of DAB389IL-2: new insights into C-domain delivery to the cytosol of target cells. 751 76

Fifty-one patients (47 evaluable) with AML, 27 in first relapse and 20 either in second relapse or refractory were treated with menogaril, 100 mg/m2/day as a 90-min infusion daily for 5 days. The complete response (CR) rate was 17% (8/47), and there was one partial response. Seven of eight responders were in first relapse with a 26% response rate among first relapse patients (7/27). The median duration of survival was 3 months for all first relapse patients and 4.3 months for all other patients. Toxicity included grades 3-4 pancytopenia and fever (100% of patients) and grades 3-4 stomatitis and hepatic enzyme elevation (25% of patients). Grades 3-4 cardiac toxicity occurred in three patients (two grade 3 arrhythmias and one heart block). All had previously received anthracyclines. Remission duration was 1.6-48+ months; two patients underwent bone marrow transplantation and continue in CR at 36+ and 48+ months. The nontransplanted patients remained in CR 1.6, 2.0, 3, 7, 14 and 27 months. Activity and toxicity of menogaril in this study were comparable to that of other clinically useful anthracyclines in AML. Further investigation of this agent in AML is warranted.
Leukemia 1995 Oct
PMID:A phase II study of menogaril (7R-O-methylnogarol) in patients with relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group. 756 2

6-Thioguanine (6-TG) was administered as a continuous i.v. infusion for 7 days to 24 patients with relapsed or refractory acute leukemia or in the blast phase of chronic granulocytic leukemia. The daily dose of 6-TG was escalated from 37.5 mg/m2 to 160 mg/m2. Stomatitis was dose-related and dose-limiting with a maximum tolerated dose of 120 mg/m2 daily. Cutaneous reactions were dose-related but not dose-limiting. The recommended dose for phase II trials in acute leukemia is 120 mg/m2 per day as a continuous infusion for 7 days. There were two complete and four partial remissions among all patients. At the suggested phase II dose of 120 mg/m2 there were two complete remissions and one partial remission in five evaluable patients.
Leukemia 1995 May
PMID:Phase I study of continuous infusion 6-thioguanine in patients with acute leukemia. 776 38


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