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)

On the basis of in vitro studies demonstrating marked synergy between mitoxantrone and high-dose cytosine arabinoside (ara-C) (HiDAC) against L5178Y murine leukemia and clinical studies showing usefulness of the combination in patients with refractory acute myeloid leukemia, a phase I study was initiated to find tolerable doses for use in patients with refractory solid tumors. Initial dose levels were mitoxantrone 2 mg/m2 infused over 30 minutes, followed by high-dose ara-C 750 mg/m2 infused over 3 hours repeated once at 24 hours (total dose 4 mg/m2 mitoxantrone and 1,500 mg/m2 HiDAC per 2-day course), with planned subsequent escalation of mitoxantrone. Moderate-to-severe myelosuppression, however, required sequential dose reduction of both agents. Nonhematologic toxicity was restricted to manageable nausea and vomiting in one-half the patients and a single episode of transient delirium of uncertain etiology. No responses were observed in 23 heavily pretreated patients with a wide variety of malignancies. On the basis of this study, doses of 187-375 mg/m2 ara-C given every 24 hours for two doses following mitoxantrone 1 mg/m2 every 24 hours for two doses would be tolerated by most patients with subsequent dose escalation in some as allowed by myelosuppression.
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PMID:Mitoxantrone and high-dose ara-C in refractory malignancies: a phase I trial. 270 36

Thirty cases of acute leukemia in patients over 15 years of age (18 males and 12 females) were treated with combinations containing mitoxantrone between January 1986 and August 1987 at the Kuwait Cancer Control Center. Acute nonlymphoblastic leukemia (ANLL) cases received mitoxantrone 10 mg/m2/day, days 1-3, cytosine arabinoside (Ara-C) 100 mg/m2 continuous daily infusion, days 1-5, and 6-thioguanine 100 mg/m2/day, days 1-5. Cases of acute lymphoblastic leukemia (ALL) received mitoxantrone 10 mg/m2/day, days 1-3, vincristine 1.4 mg/m2 days 1, 8, 15 and 22 and prednisone 40 mg/m2/day, days 1-22, then tapered down over one week. There were 16 cases of newly diagnosed ANLL, 9 cases of newly diagnosed ALL and 5 cases of relapsing leukemias. The 30 patients received 59 courses of therapy. The main toxicity was pancytopenia which occurred following all courses. It started following 75% of courses on day 8, lasted between 8-10 days and then rapidly recovered. In cases of ALL, the platelet count was much less affected in subsequent courses. Nausea and vomiting was a minor problem and occurred following 19% of courses, and in the majority was mild. Mucositis occurred following 30% of courses, and was mainly of moderate degree starting one week following the start of the course, and lasted about one week. Alopecia in the 25 newly diagnosed cases occurred in 18 cases (9 partial and 9 complete).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experience with combinations containing mitoxantrone in the treatment of adult acute leukemias. 273 80

38 consecutive, previously untreated adult patients with acute non-lymphocytic leukaemia (ANLL) were treated with BHAC-AMP (N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine, aclacinomycin A, 6-mercaptopurine, and prednisolone) therapy between March 1980 and February 1985. 25 patients (65.8%) achieved complete remission (CR). Median CR duration and median survival of patients who achieved CR were 14, and 24 months, respectively. The Kaplan-Meier analysis revealed a probability for remaining in CR of 18.0% at 5 years. Analysis of failure cases revealed that most of them were due to resistant disease. Major toxicities were infection, diarrhoea, liver dysfunction, nausea and vomiting but these were acceptable. The results indicate that BHAC-AMP therapy is comparable to the regimen with daunorubicin and cytosine arabinoside and a further clinical trial is necessary for previously untreated adult patients with ANNL.
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PMID:Behenoyl cytosine arabinoside, aclacinomycin A, 6-mercaptopurine, and prednisolone combination therapy for acute non-lymphocytic leukaemia in adults. 276 38

The current case study illustrates the innovative potential of combined medical and psychological treatment of postchemotherapy nausea and vomiting for cancer patients. A 58-yr-old male patient diagnosed with leukemia and on a weekly cytosine arabinoside (Ara-C) treatment protocol, experienced violent vomiting episodes approximately 3 hr. after each injection. Emesis was so severe that the patient considered terminating treatment. Control was attempted with antiemetics (Compazine, Reglan), an antianxiety agent (Valium), an hypnotic (Dalmane), canabinol, hypnosis, and relaxation training without success. A re-examination of these strategies employing experimental rigor and data-responsive experimental designs indicated how success can be achieved without the necessity of new interventions. The patient experienced complete emetic relief and at 3-yr. follow-up remained symptom-free.
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PMID:Combined medical and psychological treatment of postchemotherapy nausea and vomiting: a case study. 278 Sep 30

We conducted a phase II trial of deoxycoformycin (pentostatin [DCF]) in chronic lymphocytic leukemia (CLL). Eligibility criteria included age greater than 18 years, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, lymphocyte count greater than or equal to 15,000 cells/microL, international stage B or C disease (multiple lymph nodes involved and/or hemoglobin [Hgb] less than 11 g and/or platelets less than 100,000/microL) and no more than one prior treatment regimen. DCF dose was 4 mg/m2 intravenously (IV) weekly for 3 weeks and then every 2 weeks. There were 39 eligible patients (35 men and four women; median age, 63 years; median time from diagnosis to study entry, 3 years). Of these 39 patients, 31% were stage B and 33% had no prior treatment. Median laboratory values at entry were Hgb 10.5 g, WBC 96,100/microL, and platelets 93,500/microL. Nodal involvement was present in 90%, splenomegaly in 81%, and hepatomegaly in 47%. Patients received a median of nine DCF injections, with a range of four to 26. Three patients were not evaluable for response. Overall, 3% achieved a complete response (CR), 23% a partial response (PR), 28% showed clinical improvement (CI), and 38% had stable disease (SD). Associated toxicities (grade 2 or worse) observed were infections (52%), worsening of thrombocytopenia (26%) or anemia (33%), nausea and vomiting (31%), rash or pruritus (20%), and stomatitis (8%). We conclude that DCF is an active agent in CLL with acceptable toxicity.
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PMID:Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B. 278 91

Trimetrexate, a new nonclassical antifolate, was evaluated in a phase I trial in children with refractory cancer including nine with acute leukemia and 21 with solid tumors. The drug was administered as an i.v. bolus injection weekly for three doses, and courses were repeated every 28 days. The dose ranged from 35 to 145 mg/m2. Thirty patients who received a total of 33 courses were evaluable for toxicity, including 19 who were evaluable for hematological toxicity. The maximally tolerated dose for patients with a solid tumor and leukemia was 110 mg/m2. The dose-limiting toxicities were myelosuppression, mucositis and a pruritic, diffuse maculopapular rash. Other side effects observed included transient, mild elevations of serum transaminases, mild nausea and vomiting, and a local phlebitis at the site of injection at higher dose levels. A single patient with delayed drug clearance had evidence of renal toxicity with a transient increase in serum creatinine. The pharmacokinetics of trimetrexate were studied in 25 patients over the entire dose range. There was considerable interpatient variability in total drug clearance (range 9.2 to 215 ml/min/m2) and half-life (2.1 to 20 h). There was a suggestion of a correlation between plasma concentration at 24 h and the development of hematological toxicity at the highest dose level. Trimetrexate was cleared primarily by biotransformation with renal clearance accounting for only 10% of total clearance. Two metabolites of trimetrexate which inhibit the enzyme dihydrofolate reductase were identified in the urine. One of these appears to be a glucuronide conjugate.
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PMID:Pediatric phase I trial and pharmacokinetic study of trimetrexate. 295 48

Bone marrow transplantation has become an accepted treatment for malignancy (particularly leukemia and lymphoma), aplastic anemia, and certain inborn errors of metabolism. Patients require intensive care because of chemoradiation therapy toxicity, a prolonged period of immunosuppression and thrombocytopenia, graft-versus-host disease (GVHD), and the need for parenteral nutrition. Gastrointestinal and hepatic diseases are frequent post-transplant problems. They present with intractable nausea and vomiting, intestinal bleeding, diarrhea, esophageal complaints, abdominal pain, and hepatobiliary symptoms. Our clinical approach to complex transplant patients depends on the timing of signs and symptoms after marrow grafting and on the likelihood that specific disease processes are present. Each of these major problems is covered in this review.
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PMID:A problem-oriented approach to intestinal and liver disease after marrow transplantation. 304 22

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

N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) is one of the ara-C derivatives resistant to deamination. Administration of BH-AC in an intermediate (500 mg/m2) or a high dose (1000 mg/m2) resulted in maximum BH-AC plasma levels that were 10 to 20 times as high as those obtained at the conventional BH-AC dose and prolonged maintenance of comparatively high levels. High concentrations of ara-C in the plasma were observed just after BH-AC administration and at 24 hours were proportionally far higher than the ratio between the BH-AC doses administered in this study and those usually administered. To prevent the occurrence of shock, which has reportedly occurred in other studies, because of the presence of HCO-60, hydrocortisone was administered together with BH-AC in this study. In the two patients studied, no shock was observed and the only side effects were transient nausea and vomiting. The results suggest that administration of intermediate and high doses of BH-AC, accompanied by HDC, will prove a safe, effective means of enhancing the efficacy of leukemia therapy.
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PMID:Clinical use of intermediate to high dose of N4-behenoyl-1-beta-D-arabinofuranosylcytosine in children with acute leukemia. 316 31

Thirty-one patients with hairy-cell leukemia were treated with 2'-deoxycoformycin (DCF) in a National Cancer Institute of Canada multicenter trial. The DCF was administered in a cycle (4 mg/m2 iv weekly X 3), which was repeated every 8 weeks. Following a complete remission, consolidation was done with two further cycles of DCF. Of 28 patients evaluable for response, 25 obtained a complete remission; 3 had a partial response. To date there has been only one relapse; the median time with no therapy was 429.5 days (range 99-743 days). Toxicity was moderate and included nausea and vomiting, lethargy, and skin rash; with the first cycle of treatment, neutropenia and an increased incidence of fever or infection were also observed. We conclude that low-dose DCF is highly effective in treating hairy-cell leukemia.
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PMID:Efficacy of 2'-deoxycoformycin in hairy-cell leukemia: a study of the National Cancer Institute of Canada Clinical Trials Group. 329 Apr 98


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