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)

Tricyclic nucleoside phosphate (TCN-P) was selected for clinical trials because of its unusual chemical structure and activity against L1210 murine leukemia and MX-1 mammary xenograft. Inhibiting DNA synthesis, TCN-P was more toxic during S-phase of cell cycle. A phase I study was conducted in 24 patients with advanced solid cancers. The drug was given as a slow i.v. injection over 5 min on Days 1, 8, 15, and 22 of a 42-day cycle with a 2-week rest. Five dose levels ranging from 12 to 96 mg/m2 were studied with 3 to 12 patients treated at each level; a total of 106 doses was administered. The major hematological toxicity was thrombocytopenia, with a median nadir occurring at Day 34 of the cycle and first appearing at doses greater than 24 mg/m2. Anemia was seen at each dose level occurring between Days 8 and 34. Non-myelosuppressive toxic effects included stomatitis, anorexia, transient fever, nausea and vomiting, and dose-limiting hyperglycemia and diarrhea. The highest tolerated dose was 48 mg/m2. Plasma, pleural fluid, urine, and tissue samples were analyzed for TCN-P and tricyclic nucleoside (TCN) in selected patients by high-performance liquid chromatography. Plasma decay curves revealed extended retention of both TCN and TCN-P. Autopsy specimens obtained 61 days after therapy showed the highest residues of TCN-P in liver metastases and of TCN in gall bladder, bile, and pancreas. No drug was detected in urine samples of two patients. Prolonged retention and erratic plasma levels of the drug are probably due to extensive enterohepatic circulation, as well as repeated interconversion between TCN-P and TCN within cells. This weekly schedule produced unexpected clinical toxicity and should not be pursued.
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PMID:Phase I evaluation and clinical pharmacology of tricyclic nucleoside 5'-phosphate using a weekly intravenous regimen. 369 29

Antineoplaston AS2-1 is a mixture of two products of hydrolysis of Antineoplaston A10 and consists of sodium salts of phenylacetylglutamine and phenylacetic acid in the ratio of 1:4. Antineoplaston AS2-1 injections were administered to 20 patients diagnosed with 21 types of neoplastic diseases. The patients' diagnoses included: lung cancer, stage III, 4 cases; colorectal, stage IV, 3; breast, stage IV, 2; breast in remission, 1; glioblastoma, 3; head and neck, stage IV, 3; uterine cervix, stage IA, 1; chronic myelocytic leukaemia, 2; lymphocytic lymphoma, stage IV, 1; and leiomyosarcoma of the uterus, stage IVB, 1. Antineoplaston AS2-1 was administered every 6 h i.v. through subclavian vein catheter. The treatment was administered from 38 to 872 days. The highest dosage taken was 160 mg/kg/24 h. The treatment was associated with minimal side-effects, including slight nausea and vomiting in one patient, mild allergic reaction in the form of maculopapular rash in another patient and moderate elevation of blood pressure in an additional patient. One patient developed febrile reaction and three patients had mild electrolyte imbalance. Only one patient showed slight decrease of WBC. Desirable side-effects included improved healing of chronic atrophic ulceration. The response to the treatment included 6 complete remissions, 2 partial remissions, 7 cases of stabilization and 6 cases of increasing disease. Three patients are alive, well and free from cancer 5 years after the beginning of the study. The hypothetical mechanism of action of Antineoplaston AS2-1 as an anticancer agent is described.
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PMID:Toxicology studies on antineoplaston AS2-1 injections in cancer patients. 374 78

Sixty-seven patients with newly diagnosed acute nonlymphocytic leukemia (ANLL) who were considered to be poor candidates for treatment with cytosine arabinoside (ara-C)/anthracycline antibiotic therapy were treated with high-dose ara-C (HDara-C) remission induction therapy. Thirty-four of the 67 patients had a hematologic disorder before developing acute leukemia or had a history of exposure to marrow toxins, 23 patients were greater than 70 years old, and 10 patients had medical problems that were felt to be a contraindication to therapy with an anthracycline antibiotic. Forty-two percent of patients entered complete remission (CR), whereas 22% failed to enter remission because of persistent leukemia. Treatment was associated with substantial toxicity varying from nausea and vomiting to irreversible cerebellar toxicity. Thirty-four percent of patients died during therapy. Poor performance status, a low serum albumin, and a low platelet count were associated with death during remission induction therapy, whereas a high pretherapy leukemic cell mass and a large number of residual leukemic cells in the marrow after six days of therapy were associated with treatment failure due to persistent leukemia.
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PMID:High-dose cytosine arabinoside as the initial treatment of poor-risk patients with acute nonlymphocytic leukemia: a Leukemia Intergroup Study. 380 62

In experimental systems, hydroxyurea (HU) and cytarabine (ara-C) produce synergistic cytotoxicity to murine and human leukemia cells due to both cytokinetic and biochemical interactions that tend to enhance the effectiveness of ara-C. Therefore, we began a phase II trial of the combination of HU and ara-C to determine the efficacy and toxicity of this combination in treatment of patients with refractory non-Hodgkin's lymphoma. Chemotherapy began with HU 500 mg administered orally every six hours for four doses. Twelve hours following the fourth HU dose, ara-C 100 mg/m2/d was administered by continuous intravenous (IV) infusion for three days. Concomitantly with the three-day ara-C infusion, patients again received HU 500 mg orally every four hours. Cycles of therapy were repeated every 28 days. Twenty-five patients ranging in age from 26 to 70 years were enrolled in the study. Of 21 patients evaluable for response, nine (43%) obtained complete (CR) or partial remissions (PR). Most responding patients had either large-cell or cutaneous T cell lymphoma, and all but two had a performance status of 0 to 1 at entry in the study. The median survival for all responding patients was 13 months compared with 2.5 months for nonresponders. Patients obtaining a CR had a median survival of 27.5 months, and two of the four CRs remain alive and in remission at 10+ and 30+ months from achievement of CR status. The primary toxic effect of this regimen was bone marrow suppression. The median WBC nadir was 2,200 cells/microL, and the median platelet nadir was 80,000/microL. Other toxicities included mild nausea and vomiting and diffuse maculopapular rash. This biochemically rational approach to enhancing ara-C activity may have significant clinical utility and should be further explored in treatment of patients with large-cell and cutaneous T cell lymphomas.
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PMID:Sequential hydroxyurea-cytarabine chemotherapy for refractory non-Hodgkin's lymphoma. 381 8

Fifty-two adults treated previously with either acute leukemia (43 patients) or blastic-phase chronic myelogenous leukemia (nine patients) received 4-demethoxydaunorubicin (20 to 45 mg/sq m) i.v. over 2 to 3 days. Three of the ten patients with acute lymphocytic leukemia achieved a complete remission (CR) lasting 5 to 7 weeks. Five of the 28 patients with acute nonlymphocytic leukemia achieved a CR lasting 5 to 80 weeks. All remissions were induced with one course of treatment with a median time to CR of 28 days (range, 22 to 40 days). None of the patients with blastic chronic myelogenous leukemia or secondary leukemia achieved a CR. The drug was well tolerated; mucositis (36%), nausea and vomiting (35%), and hepatic dysfunction (26%) were the most common side effects. Pharmacokinetic observations on five patients demonstrated multiphasic clearance of 4-demethoxydaunorubicin and extensive formation and prolonged retention of 4-demethoxy-13-hydroxydaunorubicin; that metabolite accumulated in plasma on repeated daily dosing. 4-Demethoxydaunorubicin has sufficient antileukemic activity in both acute lymphocytic leukemia and acute nonlymphocytic leukemia to warrant a prospective comparison, in combination regimens, against the conventional anthracyclines, daunorubicin and/or doxorubicin.
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PMID:Phase I and II clinical and pharmacological study of 4-demethoxydaunorubicin (idarubicin) in adult patients with acute leukemia. 385 96

Demethoxydaunorubicin (DMDR), a new anthracycline available both for intravenous and oral administration, was given in 14 cases of leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) replacing either daunorubicin (DNR) or doxorubicin (DOX) in conventional chemotherapy regimes. In acute leukaemia (6 myeloblastic and 1 common lymphoblastic) there were 5 complete (CR) and 2 partial (PR) remissions; one patient, previously brought into remission with a regime including i.v. DMDR was thereafter maintained in CR with oral DMDR. Among the patients treated with the oral DMDR, 2 NHL cases were treated; 1 patient had a sustained remission of 12 months so far, with DMDR alone; another patient had a CR with a combined regime. In MM, one patient with very advanced disease treated with i.v. DMDR/CHOP did not respond, but three cases treated with oral DMDR plus other drugs showed a partial remission. Toxic effects were limited to brief episodes of nausea and vomiting in a few i.v. treated patients; a prolonged bone marrow depression was observed in one case only. No cardiotoxic effect was recorded.
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PMID:Intravenous and oral demethoxydaunorubicin (NSC 256-439) in the treatment of acute leukemia and lymphoma: a pilot study. 385 41

Thirty-one pediatric patients with acute leukemia who had relapsed on either 6-mercaptopurine or 6-thioguanine were treated with beta-2'-deoxythioguanosine, which was administered as an iv infusion every 12 hours for three or six doses every 2 weeks. Severe nausea and vomiting and urate nephropathy were the dose-limiting toxic effects. Therapeutic responses occurred in four of 24 children with acute lymphocytic leukemia and in two of seven with acute nonlymphoblastic leukemia.
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PMID:Phase I evaluation of beta-2'-deoxythioguanosine in pediatric patients with leukemia. 386 Feb 94

Single agent activity of aclacinomycin A or aclarubicin (ACR) for acute leukaemia in adults was as follows: complete remission was achieved in 8 of 21 (38%) with untreated patients and 7 of 41 (17%) with prior chemotherapy; thus the overall complete remission rate was 24%. The optimal dose schedule was 14 mg/m2/d daily i.v. administration, and a median total dose of 200 mg/m2 and 16 days were necessary for induction of complete remission. In combination, with behenoyl ara-C, ACR, 6-mercaptopurine and prednisolone, complete remission was achieved in 40 of 60 (67%) previously untreated patients, and 41 of 65 (63%) with prior chemotherapy; thus the overall rate was 65%. In a phase II study of ACR for solid tumours, response was achieved in carcinoma of oesophagus (1/3), stomach (12/84, 14%), gall bladder (1/4), pancreas (1/8), lung (4/30, 13%), breast (6/33, 18%), uterus (1/4), ovary (3/9, 33%), head and neck (1/5) and sarcoma (1/5). Side-effects of ACR most frequently observed were nausea and vomiting (around 30%) and a moderate grade marrow suppression was noted. An ECG change was observed in 7%, but there were no cases of chronic heart failure.
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PMID:Clinical review of aclacinomycin A in Japan. 386

Difluoromethylornithine (DFMO), a non-competitive inhibitor of ornithine decarboxylase (ODC), the rate limiting enzyme of the polyamine synthetic pathway was evaluated in a Phase I trial. Intravenous DFMO was given to twenty patients with refractory leukemia by continuous infusion in doses from 5.5 to 64 g/m2. Toxicity clearly attributable to the drug was not severe and other than nausea and vomiting did not increase with dose. The previously reported ototoxicity which occurred with the oral form appeared to be less frequent. Loss of hearing which improved when the drug was stopped was seen in four patients, three of whom were simultaneously receiving aminoglycosides. Anorexia occurred in some patients at all doses. Vomiting, necessitating dosage reduction, was a significant problem at the highest dose administered. No patient achieved a remission but there was stabilization or decrease in circulating blast cells in several patients. This growth inhibition did not appear to be dosage related.
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PMID:Phase I evaluation of intravenous difluoromethylornithine--a polyamine inhibitor. 393 6

Nine children with acute non-lymphocytic leukemia (ANLL), ages 16 months to 16 years (median 7 years), and 15 children with acute lymphocytic leukemia (ALL), ages 10 months to 18 years (median 5 years), were treated with 5-day courses of mitoxantrone (Novantrone; dihydroxyanthracenedione) as induction therapy. All the children had leukemia which was resistant to conventional therapy and all but one patient had received anthracycline therapy prior to the initiation of this trial. Three patients (two with ANLL, one with ALL) received the drug at a dose of 6 mg/m2/day i.v. for 5 days. Both patients with ANLL achieved partial remissions (PR) (105 and 87 days duration). The child with ALL failed to respond to two courses of the drug, and died of progressive disease 45 days after the institution of therapy. Twenty-one patients (14 with ALL, seven with ANLL) were treated with 8 mg/m2/day i.v. mitoxantrone for 5 days. There were three early deaths (all ALL) which were not felt to be secondary to drug toxicity. Four of the 18 children achieved complete remission (CR) (one ANLL - 35 days; three ALL - 39, 31 and 13 days). One child with ANLL achieved a PR (13 days) and one child with ALL showed improvement in his bone marrow status. Twelve children failed to respond to this therapy. Dose-limiting toxicity was not seen among the patients who received 6 mg/m2/day for 5 days. There were five patients who had mucositis and one patient who had nausea and vomiting among those patients who received 8 mg/m2/day for 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mitoxantrone in refractory acute leukemia in children: a phase I study. 401 22


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