Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 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

Phase I clinical studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA) using several dose schedules have shown acceptable toxicity and antitumor responses in acute leukemia and several carcinomas. Thirty-eight children with acute leukemia and non-Hodgkin's lymphoma were treated with AMSA in a total dose of 140 to 600 mg/sq m given as a daily i.v. infusion in 2 to 5 days. Maximal tolerated dose was 600 mg/sq m given in 5 days. Complete and partial remissions were seen in four of 18 patients with acute lymphocytic leukemia, zero of eight patients with acute nonlymphocytic leukemia, and one of five patients with non-Hodgkin's lymphoma. Marrow aplasia and remissions were also seen with lower doses. The major toxic effects were mucositis, fever, and sepsis which were dose related. Mild nausea and vomiting, transient elevation of serum glutamic oxaloacetic-acid-transaminase, and bilirubin were noted. All of these patients had had prior anthracycline therapy. Abnormal echocardiograms were seen in 14 of 23 patients who had echocardiograms done before and after AMSA. Seven developed congestive heart failure in association with sepsis in five and with epicardial disease in one. We conclude that AMSA possesses significant activity in childhood leukemia and lymphoma and that studies of AMSA in combination with other effective agents should be done.
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PMID:Phase II study of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992) in children with acute leukemia and lymphoma. 689 64

Thirteen patients with relapsed acute leukemia, 12 adults with acute nonlymphocytic leukemia, and one child with acute lymphoblastic leukemia were treated with VP 16-213, an epipodophyllotoxin analog, at a dose of 200-300 mg/m2/day X5 as a 2-hour intravenous infusion. Only four patients achieved bone marrow aplasia and three regenerated with leukemic cells. The fourth patient achieved a partial remission for 4 weeks. Toxicities included myelosuppression (WBC nadir 500/microliter), nausea and vomiting (70% of courses), mucositis (23%), esophagitis (12%), which contributed to death in one patient, hypotension (12%), and transient liver function abnormalities (12%). It is concluded that increasing the dose of VP 16-213 as employed in this study did not increase the therapeutic activity of VP 16-213 for the treatment of relapsed leukemia but did increase the risk of toxicity.
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PMID:High-dose VP 16-213 (NSC 141540) for the treatment of patients with previously treated acute leukemia. 693 27

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

A randomized study of intestinal decontamination was undertaken in 68 children with leukemia and solid tumours. Framycetin, colymycin, nystatin, and metronidazole were given in 35 neutropenic episodes in 33 children, while co-trimoxazole and lactobacilli preparation were administered in 35 episodes in 35 children. The diseases, severity of neutropenia, and incidence of infection at entry into study were comparable in the two groups. There was no significant difference in the incidence of infections developing during the phase of neutropenia. The median and range of time required to recover from neutropenia were also not different. Co-trimoxazole and lactobacilli were significantly better tolerated, there being no nausea and vomiting, no refusal to take medication, no dose reduction or change to an alternative regimen. We conclude that co-trimoxazole and lactobacilli preparation improve quality of life during a neutropenic episode and have the additional advantage of being relatively inexpensive.
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PMID:Prophylactic co-trimoxazole and lactobacilli preparation in neutropenic patients. 696 48

Indicine N-oxide is a pyrrolizidine alkaloid isolated from Heliotropium indicum, one of the widely used herbs in Ayurvedic medicine. Thirty-seven patients with solid tumors received the drug: 15 men and 22 women (mean age, 53 years). All had had prior chemotherapy, and 25 had had prior radiotherapy. Eighty-four percent had a performance status of 0-3 (Cancer and Leukemia Group B criteria). The drug was given as a short infusion over 15 minutes and repeated with a median interval of 4 weeks. Doses were escalated from 1 to 9 g/m2. A total of 55 courses were evaluable. Dose-limiting toxic effects were leukopenia and thrombocytopenia, and the toxicity was cumulative with repeated doses. Other toxic effects included nausea and vomiting, anemia, and hepatic dysfunction. The hematologic toxicity tended to be more pronounced in patients with hepatic dysfunction, poor marrow reserve, and heavy prior chemotherapy and radiotherapy. There were no complete or partial responses. One patient with skin melanoma and another with ovarian carcinoma had improvement lasting 2 months. The maximally tolerated dose is 9 g/m2 in our population. A recommended dose for therapeutic study is 7 g/m2. High-risk patients should be started at a dose of 5 g/m2. The treatment may be repeated at 4-week intervals with close monitoring of wbc and platelet counts. Dose reductions may be necessary for repeated courses.
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PMID:Phase I study of indicine N-oxide in patients with advanced cancer. 709 66

Four patients with acute nonlymphoblastic leukemia and one malignant teratoma refractory to conventional chemotherapy were treated with high doses of cytosine arabinoside (HD ARA-C). They received up to 12 cycles of 1.8 to 3 g/m2 every 12 hours applied by 2-hour infusions. A total of 55 HD ARA-C infusions was performed. All leukemic patients responded. A complete clearance of blasts from the bone marrow was observed in two patients following 8-12 cycles of 3 g/m2. However, relapses occurred after three and seven weeks, in one case with resistance to HD ARA-C. The patient with malignant teratoma did not respond. No severe toxicity emerged even after repeated applications. Adverse reactions included moderate nausea and vomiting (4 patients), diarrhea (2 patients), hepatic dysfunction (1 patient), bone pain (1 patient), blurred vision (1 patient), conjunctivitis (1 patient), and exanthema with partial epidermiolysis (1 patient). Granulocytopenia occurring between 3-8 days after having started the therapy, subsided within 4-25 days. Plasma levels of ARA-C and the metabolite uracil arabinoside (ARA-U) were monitored. At steady state plasma concentrations of ARA-C were 32-97 microM (8-24 micrograms/ml). ARA-C disappeared from the plasma mono- or biphasic with a terminal half-life (t50%) of 7.8-12.6 minutes. The total clearance (Cl) of ARA-C varied between 1.7 and 2.9 liters/kg . h, and the distribution volume (Vss) between 0.44 and 0.86 liters/kg. Cerebrospinal fluid (CSF) levels of ARA-C reached 10-15% of steady state concentrations in plasma.
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PMID:Clinical results and pharmacokinetics of high-dose cytosine arabinoside (HD ARA-C). 710 69

Phase I study of a new antitumor antibiotic, neothramycin which belongs to anthramycins was performed by a cooperative study group involving 15 major institutions. A total of 63 cases including 42 various solid tumors and 21 hematologic tumors refractory to standard treatments underwent the study during June 1979 to June 1981. Doses of single injection were escalated from an initial dose of 2 mg/m2 estimated by one twentieth of LD10 in mice up to 60 mg/m2. The most frequent and severest toxicity was nausea and vomiting seen in about the half of patients being administered dosages ranged from 24 mg/m2 to 40 mg/m2, and 3 out of 4 patients received dosages exceeding 50 mg/m2 required clinical managements; moreover, 1 out of 2 patients administered 60 mg/m2 was ranked as grade 4 of the criterion of toxicities in WHO handbook. Other clinical toxicities such as skin rash, hepatotoxicity or nephrotoxicity observed in the minority of the patients were reversible. Furthermore, hematologic toxicity was extremely mild and appeared not to be dose dependent. One patient with chronic myelogeneous leukemia had a hematological improvement and the other with esophageal cancer had a partial response. The result indicates that a dose limiting factor of neothramycin is nausea and vomiting, and a maximum tolerated dose of a single injection is 60 mg/m2. A dose schedule of 30-40 mg/m2 appears to be an optimal dose for Phase II study.
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PMID:[Phase I study of a new antitumor antibiotic, neothramycin]. 718 35

A phase I-II study of N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BH-AC) was conducted by a cooperative study group. In phase I study, a total of 126 patients, 64 of whom had metastatic solid tumors and 62 of whom had leukemia, were administered BH-AC in a single IV dose at day 1 only or in daily IV doses for 3 to 21 days, with dose ranges of 1.5--10.0 mg/kg. Side effects included nausea and vomiting, which were significantly less in incidence and severity than those observed with ara-C. Myelosuppressive toxicity became severe with doses 3.6--5.0 mg/kg per day x 10 days. In phase II study, a total of 37 adult patients with acute leukemia were entered in the study. Responses were noted, with an overall rate of 35% complete remission. Of th 26 patients with AML, there were 13 CR. The recommended schedule of treatment for BH-AC, based on our data, is daily infusion of 4--5 mg/kg over 3 h for approximately 3 weeks. The results with BH-AC in patients with acute leukemia are superior to those which have been reported for ara-C.
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PMID:Phase I--II study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine. 723 52

All Phase II studies with diglycoaldehyde with leukemia and solid tumors have been reviewed. The dose schedules employed ranged from 1.5 to 2.0 g/m2/day for 3 to 5 days. The most common side effects have been gastrointestinal (nausea and vomiting), which occurred in 22% of the patients. Renal toxicity (rise in BUN, creatinine, and urinary proteins) was seem in 17% of the patients treated. Other infrequent toxicities include hypocalcemia (9%) and local complications such as phlebitis. Leukopenia, thrombocytopenia, positive Coombs' test and impairment in coagulation profile were also reported. In contrast to the hints of therapeutic efficacy described during Phase I trials, in phase II trials no activity was noted among 96 patients with solid tumors and only minimal antileukemic action among 49 other patients. These disappointing Phase II trials coupled with prominent toxicities have prompted the decision to terminate further clinical testing. This report summarizes all clinical observations as an example of circumstances which curtail clinical testing of anticancer drugs.
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PMID:Clinical trials with diglycoaldehyde (NSC-118994): review and reasons for withdrawal from clinical trial. 734 55


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