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

Diaziquone (AZQ) and etoposide (VP-16) were administered as simultaneous 5-day continuous infusions to 27 patients with acute leukemia (22 with acute myeloid leukemia (AML), three with chronic myeloid leukemia in blast crisis (CML-B), and two with acute lymphocytic leukemia) at four different doses in a phase I trial. Gastrointestinal toxicity, primarily stomatitis, was dose limiting, occurring in six of 10 patients at the highest dose level. Diarrhea was the only other grade 3 toxicity noted (three of 10 at the highest dose level). The duration of bone marrow aplasia was excessive at the highest dose (median 48 days to granulocytes greater than 500/mm3, range 33-67) but acceptable (31 days) at the maximum tolerated dose: AZQ 28 mg/m2/day x 5 days, VP-16 150 mg/m2/day x 5 days. Complete remissions were seen in seven patients (six AML, one CML-B) and a partial remission in one patient with AML. The median duration of unmaintained complete remission was 3 months (range 1.5-26+).
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PMID:Continuous infusion diaziquone and etoposide: a phase I study in adult patients with acute leukemia. 231 18

Forty-one children with refractory acute nonlymphocytic leukemia (ANLL) were treated from March 1975 to February 1979 with a schedule-dependent combination of methotrexate (MTX) and L-asparaginase. Intravenous (IV) MTX was followed 24 hours later by IV L-asparaginase (10,000 units [U]/m2). The MTX dose was started at 60 to 100 mg/m2 and was escalated by 20 to 40 mg/m2 as tolerated. This sequence was repeated every 7 to 10 days. Eight patients (20%) achieved a complete remission (CR) and six others had a partial response (PR), with clearance of blasts from the peripheral blood and reduction of bone marrow blasts to less than 25% of nucleated marrow cells. Responding patients received a median maximum MTX dose of 120 mg/m2 (range, 60 to 220 mg/m2). The median number of courses required to achieve a CR was 6 (range, 2 to 13 courses). Toxicity consisted of allergic reactions to L-asparaginase (n = 12), stomatitis (n = 6), minimal elevation of hepatic enzymes (n = 2), and hyperglycemia (n = 1). Treatment was given on an outpatient basis in 95% of all courses. The data indicate that this combination therapy has antileukemic activity and is relatively nontoxic in childhood ANLL.
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PMID:Methotrexate plus L-asparaginase. An active combination for children with acute nonlymphocytic leukemia. 234 Apr 62

Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7-3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7-3-7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5-2 or 5-2-5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7-3 and 59% of 7-3-7 patients; 7-3-7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7-3 and 18 months for 7-3-7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7-3 and 27 months for 7-3-7 (P = .01). Survival appeared to be prolonged with 7-3-7 in patients aged less than 55 years, with a median of 9 months for 7-3 as compared with 17 months for 7-3-7 (P = .03). In older patients (aged greater than or equal to 55 years), 7-3-7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7-3 and 15 days for 7-3-7. Hematologic toxicity was more severe for 5-2-5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.
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PMID:Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group. 240 18

The Southeastern Cancer Study Group conducted a phase I-II trial of sequentially administered 5-azacitidine and amsacrine in patients with refractory adult acute leukemia from September 1980 to March 1983. The 5-azacitidine was administered by continuous iv infusion on Days 1-4 at doses ranging from 112 to 200 mg/m2/day, while amsacrine was given at doses ranging from 75 to 150 mg/m2/day on Days 5-8. The doses of 5-azacitidine and amsacrine were alternately escalated through six dose levels during the phase I portion of the trial. Of 128 patients entered, 102 (80%) were evaluable for response. Remission was achieved in 13 of 80 evaluable patients with acute myeloid leukemia, in one of 12 evaluable patients with acute lymphoid leukemia, and in none of 11 patients with blastic transformation of chronic granulocytic leukemia. Three remissions occurred in patients with acute myeloid leukemia who were refractory to initial induction chemotherapy with cytarabine and anthracycline combination chemotherapy. Remissions were relatively durable, lasting a median of 28 weeks in the 13 patients with refractory acute myeloid leukemia (range, 14-54 weeks). Toxic effects included universal severe myelosuppression, hyperbilirubinemia at a frequency and severity similar to those seen with amsacrine used as a single agent, moderately severe stomatitis and diarrhea, three incidents of amsacrine-related cardiac dysrhythmia, and a single case of probable drug-related cardiomyopathy. This combination has activity in the treatment of myeloid leukemia, which is primarily resistant to cytarabine and anthracyclines, and could have a role in primary management.
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PMID:Sequentially administered 5-azacitidine and amsacrine in refractory adult acute leukemia: a phase I-II trial of the Southeastern Cancer Study Group. 241 Jan 19

The clinical efficacy of fluconazole at doses of 100-400 mg daily given intravenously in the treatment of 6 cases of deep mycosis complicated with leukemia was evaluated. Types of leukemia as underlying disease were acute lymphatic leukemia in 4 patients (included post bone marrow transplantation in 2 patients), acute myelocytic leukemia in 1 and acute myelomonocytic leukemia (AMMoL) in 1. Causative fungi were Candida in all patients. Diagnoses established were pulmonary or bronchial candidiasis in 3 patients, candiduria in 2 and suspected candidemia accompanied with stomatitis in 1. A patient with candiduria died from AMMoL thus the evaluation of efficacy was made with 5 patients. Overall clinical efficacies were judged to be good in 3 cases of pulmonary or bronchial candidiasis and in 1 case of suspected candidemia accompanied with stomatitis and excellent in 1 case of candiduria with an efficacy rate of 100%. No side effect, either subjective or objective, was reported with any patient. In clinical laboratory tests, elevations of serum transaminase and Al-P were observed in 2 patients and a rise of S-Cr. in 1, but all these abnormalities were judged to be related to the drugs for leukemia treatment.
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PMID:[Clinical evaluation of fluconazole in the case of deep mycosis associated with leukemia]. 254 Mar 57

13 patients with refractory or relapsed acute lymphoblastic leukemia (ALL) and 7 patients with acute myeloid leukemia (AML) were treated with a regimen that included idarubicin 12 mg/m2 intravenously daily for 3 d plus cytarabine 2 g/m2 by infusion over 3 hours daily for 3 d. There were 10 remissions (ALL:7; AML:3) in the 15 relapsed patients and 4 (ALL:3) in the 5 patients with primary refractory disease. Severe myelosuppression was observed in all patients. Toxicity of this regimen caused nausea and vomiting, stomatitis, infections and/or liver enzymes increase. Cardiac toxicity was not observed. 2 patients died in aplasia of Gram-negative septicemia and brain hemorrhage. In conclusion, the combination of idarubicin and intermediate-dose cytarabine (IDARA-C) seems to be highly effective and sufficiently well-tolerated for the treatment of refractory and relapsed acute leukemias.
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PMID:Idarubicin in combination with intermediate-dose cytarabine in the treatment of refractory or relapsed acute leukemias. 258 57

In a prospective randomized trial, the pending question was addressed whether Cytosine arabinoside (Ara-C) should be applied at high or intermediate dose to patients with relapsed or refractory acute myeloid leukemia. Based upon the previously established regimen of the sequential application of Ara-C and Mitoxantrone (S-HAM) patients below 60 years of age were randomized to receive Ara-C at either 3.0 g/m2 vs 1.0 g/m2 per dose while older patients were randomly assigned to either 1.0 g/m2 or 0.5 g/m2 Ara-C. At the present early stage 51 patients have entered the study and 37 are currently evaluable for response and toxicity. Complete remissions were achieved in 14 of 28 patients below 60 years of age and in 3 of 8 older cases. Predominant side effects consisted of nausea and vomiting, diarrhea and stomatitis. Further recruitment of patients and longer follow-up is required for the assessment of the various treatment arms.
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PMID:Age related randomized comparison of sequentially applied high-dose versus intermediate dose cytosine arabinoside in combination with mitoxantrone (S-HAM) in the treatment of relapsed and refractory acute myeloid leukemia: study design and preliminary results. 265 90

21 patients with hematological neoplasias (8 ALL, 4 AML, 4 NHL, 5 HD) were treated with high dose therapy and autologous bone marrow rescue (ABMT). At the time of ABMT 12 patients were in CR, 6 in PR and 3 in relapse. 66% of the patients were at high risk at the time of diagnosis. Before ABMT patients received an ablative regimen such as cyclophosphamide or ARA-C, VP-16, DNR and 12 Gy TBI in 6 fractions. In 9 patients the bone marrow was treated in vitro with monoclonal antibodies and complement. The hospital stay was a median 33 (24-57) days and isolation 19 (9-49) days. Complications were septicemia (7), herpes stomatitis (7), infections (6), fungal sepsis (1) and hemorrhagic cystitis (2). Late complications (up to 6 months after ABMT) were pneumococcal sepsis (1), cerebral toxoplasmosis (1) and herpes zoster (3). 10 of 19 evaluable patients are alive and relapse-free 1-33 months (median 10) after ABTM, and 3 of 10 more than 2 years later: 4 of 5 were transplanted in 1. CR, 4 of 6 in greater than or equal to 2. CR and 2 of 8 in PR. 4 patients are living in therapy sensitive relapse 2, 11, 11 and 39 months after ABMT in 2. CR or PR. 5 patients died 1-13 (median 3.5) months on relapse, 2 of 21 from septicemia. The morbidity of ABMT is comparable with conventional high dose chemotherapy. Relapse-free survival was significantly influenced by the remission status at ABMT. Long-term survivors can be expected even in patients with high risk hematological malignancies. However, only wider trials will serve to establish the efficacy of ABMT.
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PMID:[Autologous bone marrow transfusion in the treatment of adults with hematologic neoplasms. Experiences from Bern]. 266 30

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of mitoxantrone are reviewed. Mitoxantrone, an aminoanthraquinone that was synthesized in 1979, belongs to a new chemical class of agents known as the anthracenediones. It possesses antiviral, antibacterial, immunomodulatory, and antitumor activity. The drug's antitumor activity is attributed to its interaction with DNA topoisomerase II, and its interaction with human cells may also involve nonintercalary, electrostatic interactions. Mitoxantrone is poorly absorbed orally and is most commonly administered intravenously. The drug is rapidly distributed into the red blood cells, white blood cells, and platelets, followed by deep-tissue sequestration. Mitoxantrone has demonstrated clinical efficacy in the treatment of leukemia, lymphoma, and breast cancer. As a single agent, mitoxantrone has a response rate of roughly 30% in acute nonlymphocytic leukemia or acute myeloid leukemia. In combination with other standard agents (cytarabine, vincristine, and prednisone), the response rate may reach 60%. In breast cancer, mitoxantrone's response rate as a single agent is 25-30%, while combination regimens produce response rates of 60% or more. The drug can cause cardiotoxicity with cumulative doses. Other adverse effects include myelosuppression, nausea and vomiting, stomatitis, mucositis, and alopecia. The cost of mitoxantrone is comparable to that of doxorubicin, but it is substantially more expensive than daunorubicin. Mitoxantrone is an important new agent with antitumor activity in leukemia, lymphoma, and breast cancer. In most situations, mitoxantrone will be considered second-line treatment or a restricted-use item because of its high cost and because of the lack of FDA approval for indications other than acute nonlymphocytic leukemia.
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PMID:Mitoxantrone: a novel anthracycline derivative. 304 48

Seventeen patients with relapsed or refractory acute nonlymphocytic leukemia were treated with 14 mg/m2 of mitoxantrone given in a 30-minute infusion daily for three days. If the day fourteen bone marrow showed residual leukemia, a second course was given at the same dose for two days. Eight patients (47%) entered complete remission. Three patients (17%) had a partial response, four (24%) did not respond, and two (12%) died with hypoplastic marrows during treatment. Seven of the 12 relapsed patients entered a complete remission, as did one of the five refractory patients. Toxicity was acceptable; prolonged myelosuppression, moderate hepatic toxicity, and stomatitis were the only problems. Several dose schedules of mitoxantrone have been studied by other investigators with varying results. The three-day schedule in the present study is similar to the schedule used for common induction regimens employing anthracycline drugs. On the basis of its activity and acceptable toxicity in relapsed and refractory ANLL patients, we feel that this schedule could be safely combined with other agents in future studies.
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PMID:Mitoxantrone in relapsed or refractory acute nonlymphocytic leukemia. 338 61


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