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)

Homoharringtonine (HHT) is a cephalotaxine alkaloid with reported efficacy in acute myelogenous leukemia (AML). In a phase II trial, we evaluated HHT 5 mg/m2 by continuous infusion daily for 9 days in patients with relapsed or refractory acute leukemia and blastic phase of chronic myelogenous leukemia (BLCML). Sixty-six patients were entered. There were 40 males and 26 females with a median age of 41 years (range 15-81). Of 43 patients with relapsed AML, seven achieved a complete remission (16%, 95% confidence interval 5%-27%). Although 11 patients with AML primarily resistant to an anthracycline/cytarabine combination did not respond, two of three patients primarily resistant to low-dose cytarabine achieved complete remission. No patients with acute lymphoblastic leukemia, biphenotypic leukemia, or BLCML responded. Hypotension during the administration of HHT was the most difficult toxicity encountered, requiring multiple interruptions of therapy in several patients and the administration of intravenous saline. Fluid retention and weight gain occurred in 29% of patients. Transient asymptomatic hyperglycemia was observed in 63% of patients. Other toxicity was mild and included nausea and vomiting, diarrhea, mucositis, hepatic dysfunction, and cardiac arrhythmias. As expected, severe myelosuppression occurred in all patients. HHT is well tolerated, but with unique problems associated with administration. It has demonstrable efficacy in pre-treated patients with AML, but its role in the treatment of this disease remains to be defined.
Leukemia 1992 Nov
PMID:Homoharringtonine is safe and effective for patients with acute myelogenous leukemia. 143 2

Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. Seventeen males and five females were treated, with a median age of 40 years (range 19-63). There were five remissions in 14 patients with relapsed AML and none of eight responders in patients with primary refractory AML. None of the three patients treated at 1.5 mg/m2 dose level of HHT responded. Of three patients treated at the 3 mg/m2 dose level, there was one complete remission. At both 4 mg/m2 and 5 mg/m2, two of eight patients achieved complete remission. Four of the five remissions occurred in patients with acute promyelocytic leukemia. Drug induced pancytopenia was universal, and hypotension and fluid retention were more common at the higher dose levels. Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation.
Leukemia 1992 Nov
PMID:Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia. 143 3

In this paper a number of anticancer agents of natural origin will be presented. Hydroxycamptothecin (HCPT) was found to produce a strong inhibitory action on a variety of animal tumors. It is also effective for treatment of patients with gastric carcinoma, liver carcinoma, tumor of head and neck or leukemia. Pharmacologic studies showed that it could depress S phase of tumor cells significantly and cause formation of cellular chromatid breaks. By means of alkaline elution and nick translation methods it has been proved that HCPT induced DNA single strand breaks remarkably. Homoharringtonine (HHRT) was shown to be effective against acute leukemia. Recent experiments in tumor-bearing mice indicated that (HHRT) could diminish tumor metastasis. Using molecular hybridization technique it was demonstrated that (HHRT) decreased the content of c-myc RNA in the cytoplasm but not in the nuclei. Lycobetaine (LBT) possessed strong inhibitory effects on a number of ascites tumors. In clinical trials it was effective against ovarian and gastric carcinomas. It is able to intercalate into DNA. Oxalysine (OXL) is a new antibiotic and shown to be effective against tumor metastatis. When used in combination with 5-FU, its anticancer action could be enhanced. Other natural compounds such as indirubin, beta-elemene, irisquinone, oridonine, norcantharidin and PSP have been also found to possess antitumor action.
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PMID:Recent advances in pharmacologic study of natural anticancer agents in China. 184 13

91 patients with acute nonlymphoblastic leukemia (ANLL) were treated with Homoharringtonine, Cytosine arabinnoside, Thioguanine (HAT) and/or Daunorubicin, (Adriamycin) Cytosine arabinnoside, Thioguanine D(A) AT protocols. The total CR rate was 68.1% with a median remission duration of 20.3 months, and the expectant survival rate in 5 years (Kaplan-Meier method) was 39%. The CR rate and the CR duration projected by HAT and D (A) AT protocols were very similar. After 20 prognostic factors from both clinical and laboratory examinations prior to treatment had been analysed, we concluded that (1) The CR rate was improved by increasing the dose of induction chemotherapy; (2) The patients might have longer remission and survival if they obtained remission in 2 courses of treatment; (3) The remission durations were comparable between the individuals receiving and not receiving maintenance chemotherapy.
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PMID:[Analysis of the therapeutic efficacy and prognostic factors of intensive chemotherapy in 91 patients with acute nonlymphoblastic leukemia]. 240 Nov 66

The in vitro induced differentiation of a number of human leukemia cell lines by chemical inducers not only provides a valuable model system for the study on the mechanism of hematopoietic cell proliferation and differentiation at both cellular and molecular levels, but also reveals a new prospect in the treatment of leukemia. In order to find out the possibility of applying inducing agents to the patients with various types of leukemia, the bone marrow cells in primary culture from 50 patients with leukemia were tested for their inducibility in response to the inducers. Only M3 leukemia bone marrow cells can be markedly induced by retinoic acid to the myeloid terminal cells with positive NBT reduction while the cells of other types respond with uncertainty. TPA is able to cause a macrophage-like differentiation in bone marrow cells of all types of leukemia except M1. However, the leukemic cells of chronic myelogenous leukemia in lymphocytic blast crisis will lose response to TPA. The cultured bone marrow cells of acute lymphocytic leukemia respond neither to retinoic acid nor to TPA. Homoharringtonine, a chemotherapeutic drug used in the so-called HOAP regimen for acute nonlymphocytic leukemia, seems to possess the capability of inducing HL-60, the promyelocytic leukemia cell line, to NBT positive myeloid terminal cells, although the inducing effect is weaker than retinoic acid.
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PMID:Heterogenous response of primary cultured bone marrow cells of patients with different varieties of leukemia to differentiation inducers. 250 3

Homoharringtonine (HHT) is a new plant alkaloid originally isolated in the People's Republic of China. Preliminary studies have suggested antitumor activity in several neoplastic diseases. We treated 49 patients with relapsed or resistant acute leukemia with escalating doses of homoharringtonine administered by continuous infusion. Three dose levels were examined: 5 mg/m2 for seven days, 7 mg/m2 for seven days, and 5 mg/m2 for nine days. Of 28 patients with acute nonlymphoblastic leukemia who received cumulative doses of 45 to 49 mg/m2, seven patients (25%) achieved complete remission. Four of these remissions occurred in a subset of ten patients previously resistant to two or more induction attempts with conventional chemotherapy. There were no remissions in three patients with secondary leukemia or in seven patients with acute lymphoblastic leukemia. Reversible hypotension, fluid retention, diarrhea, and tumor lysis syndrome were the major toxic effects of this treatment. Our results indicate that homoharringtonine is an effective new drug for the treatment of acute nonlymphoblastic leukemia and that this drug does not share cross-resistance with conventional antileukemic agents. The recommended dose is 5 mg/m2/d administered by continuous infusion for nine days.
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PMID:Homoharringtonine: an effective new drug for remission induction in refractory nonlymphoblastic leukemia. 388 29

Homoharringtonine is one of several Cephalotaxine esters which have shown experimental antineoplastic activity as well as anti-leukemia effects in patients in China. In a Phase I trial of homoharringtonine administered daily X 5 by bolus intravenous injection, the dose limiting toxicity was hypotension and the maximum tolerated dose was 3.5 mg/m2/d X 5. Evidence of drug induced cardiac irritability with resulting ventricular and atrial dysrhythmias was seen. Minimal myelosuppression was seen at this dose. Treatment of patients by 5 day continuous intravenous (rather than bolus) infusion resulted in more pronounced myelosuppression and clinically significant but tolerable hypotension. Significant reduction of white blood cell and platelet counts occurred at a dose of 3.5 mg/m2/day. Further investigations of the hypotensive and cardiac effects of homoharringtonine and Phase II trials using continuous infusion are indicated.
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PMID:Homoharringtonine: a phase I evaluation. 406 21

Homoharringtonine is one of a group of cephalotaxine esters reported by the Chinese to have significant antitumor efficacy, with particularly good activity in human leukemias. Preclinical antitumor activity against P388 leukemia, colon 38 carcinoma, and mammary carcinoma led to phase I trials which are currently nearing completion in this country. The phase I study reported here used a single infusion of homoharringtonine over 90 minutes given every 21 days. Dose-related and life-threatening hypotension, without significant myelosuppression, was the dose-limiting toxic effect. The mechanism of hypotension is not understood but it is not related to cardiac arrhythmias. Myelosuppression was not seen regularly. We do not recommend this schedule for phase II trials.
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PMID:Phase I trial of homoharringtonine. 688 57

Homoharringtonine and harringtonine are esters of cephalotaxine and are naturally occurring alkaloids in certain coniferous trees in China. These compounds have been shown to have activity against certain types of leukemia in cell cultures, experimental animals, and initial clinical trials in China, and will undergo Phase I trials in several institutions. A gas chromatographic mass spectrometric technique was developed for the quantification of both drugs in serum. One drug serves as internal standard for the other. The drugs are extracted from serum with dichloromethane and are quantified by monitoring the protonated molecular ions of the trimethylsilyl derivatives obtained by chemical ionization (methane). Masses monitored are: m/z = 690 for homoharringtonine and m/z = 676 for harringtonine. Detection limit: 10 ng ml-1 (20 nmol); reproducibility: 1.6-15.0% in the 0-200 ng ml-1 range. Serum levels of harringtonine reached 145 ng mg-1 upon intraperitoneal injection of 3 mg kg-1 in BDF-3 mice.
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PMID:Quantification of homoharringtonine and harringtonine in serum by chemical ionization mass spectrometry. 716 86

Homoharringtonine (HHT) is a new drug with antileukemic activity which is currently tested for treatment of acute and chronic leukemias, either alone or in combination with other agents. Since HHT showed a low efficacy in refractory and relapsed acute leukemia and in the blastic phase of chronic myeloid leukemia (CML) which are frequently characterized by an overexpresion of the multidrug resistance (MDR)-related P170-glycoprotein, we postulated a relationship between the poor antileukemic effect of HHT in these leukemias and the expression of P170-glycoprotein. For this reason, sensitive (LOVO109 and CEM) and MDR (LOVO DX and CEM VLB) cell lines were exposed to HHT with or without some MDR modifiers, namely, Cyclosporine A (CyA), the Cyclosporine derivative SDZ PSC 833 (PSC), and the D-isomer of Verapamil (DVRP). It was found that MDR cells were about 15 times more resistant to HHT than non-MDR cells, and that resistance to HHT was significantly decreased by all the MDR modifiers that were tested. This in vitro study showed that HHT belongs to the category of MDR-related drugs, like anthracyclines, vinca alkaloids, epipodophylline derivatives, and taxol.
Leukemia 1995 Mar
PMID:MDR-related P170-glycoprotein modulates cytotoxic activity of homoharringtonine. 788 49


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