OBJECTIVETo compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.

METHODSIn this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.

RESULTS56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.

CONCLUSIONTAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Dactinomycin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Etoposide ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Methotrexate ; administration & dosage ; Prospective Studies ; Recurrence ; Remission Induction

BACKGROUNDMagnetic targeting therapy may be a new method for the treatment of malignent tumors. The purpose of this study was to investigate the localization and distribution of ferrofluid microsphere of human serum albumin methotrexate (FM-HSA-MTX) carriers in the brain and to explore the magnetic targeting chemotherapy for malignant brain tumor.

METHODSNinety SD rats were divided into three groups: targeting group, non-magnetic targeting group, and control group. Synthesized FM-HSA-MTX carriers (MTX 25 mg/kg) were injected into the systemic circulation via the caudal vein (magnetic targeting group, n = 30). A 0.6 T magnetic field was placed around the right hemisphere. The non-magnetic targeting group (n = 30) was administered with FM-HSA-MTX without external magnetic field, meanwhile the control group (n = 30) was treated with MTX and a magnetic field. Random serial sacrifices (n = 10) were conducted at 15, 30 and 45 minutes after drug administration. Bilateral hemispheres were collected respectively, and analyzed for total MTX content.

RESULTSMTX content in the right hemisphere of the magnetic targeting group was significantly higher than that in the other two groups at 15, 30 and 45 minutes after drug administration (P < 0.05) No difference was seen between the non-targeting group and control group. In the magnetic targeting group, MTX returned to the peak level [(0.564 +/- 0.018) mg/g, q15-45 = 32.252, P < 0.05] 45 minutes after the injection but it deceased in the other two groups [non-magnetic targeting group: (0.060 +/- 0.015) mg/g, q15-45 = 9.245, P < 0.05, control group: (0.074 +/- 0.045) mg/g, q15-45 = 6.299, P < 0.05]. In the magnetic targeting group, the concentration of MTX in the right hemisphere was significantly higher than that in the left hemisphere (t45min = 21.135, P = 0.000) but no difference was observed between bilateral hemispheres in the other two groups (non-magnetic targeting group: t45min = 0.434, P = 0.670; control group: t45min = 0.533, P = 0.600).

CONCLUSIONIn the presence of the external magnetic field, FM-HSA-MTX can distribute successfully in the targeting areas of the brain.

Animals ; Antineoplastic Agents ; administration & dosage ; Brain ; metabolism ; Drug Carriers ; Magnetics ; Methotrexate ; administration & dosage ; pharmacokinetics ; Microspheres ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; administration & dosage ; pharmacokinetics

PURPOSETo exam the relationship between HER2 over-expression and different adjuvant chemotherapies in breast cancer.

PATIENTS AND METHODSA total of 1625 primary breast cancer patients who received post-surgery adjuvant chemotherapy in Tianjin Cancer Hospital, China, from July 2002 to November 2005 were included in the study. Among them, 600 patients were given CMF (CTX+MTX+5-Fu) regimen, 600 given CEF (CTX+E-ADM+5-Fu) regimen, and 425 given anthracyclines plus taxanes regimen, with mean follow-up time of 42 months.

RESULTSIn CMF treatment group, the 3-year disease free survival (DFS) in HER2 over-expressed patients was lower than that of the HER2-negative ones (89.80% vs 91.24%, P=0.0348); in node-positive subgroup, the 3-year DFS was 84.72% in HER2 over-expressed patients, and 90.18% in the HER-2-negative ones (P=0.0271). Compared to CMF regimen, anthracyclines and anthracyclines plus taxanes regimens are more effective (P<0.05) in node-positive HER2 over-expression than those in the node-negative.

CONCLUSIONHER2 over-expression is an independent index for predicting poor prognosis and short DFS for breast cancer patients. HER2 over-expressed patients are resistant to CMF regimen chemotherapy, but sensitive to anthracyclines-based or anthracyclines plus taxanes regimen. HER2 expression can be taken as a marker for therapies in breast cancer.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Breast Neoplasms ; chemistry ; drug therapy ; mortality ; Cyclophosphamide ; administration & dosage ; Epirubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Humans ; Methotrexate ; administration & dosage ; Middle Aged ; Receptor, ErbB-2 ; analysis

OBJECTIVETo develop a novel drug dilivery system based on calcium phosphate cement (CPC) with methotrexate (MTX) as a model drug and to study its drug release in vitro.

METHODSThree MTX mass fractions (0.1%, 0.2%, and 0.5%) were tested after solidification, and the compound of CPC-MTX were put into the simulated body fluid at 37 degrees C. The concentration of MTX was tested by high-performance liquid chromatography at day 2, 5, 10, 16 hours, 1, 2, 3, 5, 8, 10, 15, 20, 25, 30, 35, 40, and 45 days. The drug dilivery curves were drawn and drug dilivery rules were analyzed.

RESULTSMTX was released slowly and stably from the compound of CPC-MTX. Remarked prophase of drug release was noted, which conformed with the Higuchi equation. The drug release rate and concentration was related with the concentration of MTX in compound but not with the thickness and shape of CPC. The releasing time was not affected by the concentration of MTX.

CONCLUSIONA stable drug dilivery system can be developed by loading proper concentration of MTX into CPC.

Calcium Phosphates ; chemistry ; Chromatography, High Pressure Liquid ; Delayed-Action Preparations ; Kinetics ; Methotrexate ; administration & dosage ; analysis

A 13-year-old male and a 15-year-old female presented with optic disc edema associated with chronic recurrent uveitis. While the ocular inflammation responded to high doses of oral prednisolone, the disc edema showed little improvement. After oral administration of methotrexate, the disc edema and ocular inflammation were resolved, and the dose of oral corticosteroid could be reduced.
Administration, Oral ; Adolescent ; Chronic Disease ; Female ; Glucocorticoids/administration & dosage ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Methotrexate/administration & dosage ; Papilledema/drug therapy/*etiology ; Prednisolone/administration & dosage ; Recurrence ; Uveitis/*complications/drug therapy

A 40-year-old female visited our clinic for visual disturbance of the right eye, in which a few creamy-yellow retinal lesions and visual field constrictions were noted. She had been treated for primary CNS lymphoma and was in complete remission. After failure to follow-up for three months, she lost vision in the right eye, at which time active panuveitis was seen. Decreased vision and field constriction was observed in the left eye. Her left eye showed a granular pattern and dye leakage from the vessels and disc on fluorescein angiography and small RPE humps were seen in optical coherence tomography (OCT). Diffuse large malignant B-cells with strong immunoreactivities with CD20 immunostaining were seen in the epiretinal membrane biopsy specimen. Intravitreal injections of methotrexate (MTX) (800 microgram/0.1 ml in the right eye, 400 microgram/0.05 ml in the left eye) were performed twice weekly for one month, once weekly for the following month, once every two weeks for the next month, followed by nine monthly injections. Both eyes were free from malignant cells on vitreous biopsy six months later. There was no leakage seen by angiography, but the granular pattern persisted. Visual field constriction was slightly improved, and the small RPE humpsdetachments seen in OCT disappeared. EOG Arden ratio was decreased in both eyes, and b wave amplitude of scotopic ERG was decreased in the left eye. She was free from recurrence until six months later. No ocular complications except minimal opacity of the crystalline lenses were noted in both eyes.
Adult ; Antimetabolites, Antineoplastic/*administration & dosage ; Drug Administration Schedule ; Eye Neoplasms/*drug therapy ; Female ; Humans ; Injections ; Lymphoma/*drug therapy ; Methotrexate/*administration & dosage ; Treatment Outcome ; Vitreous Body

OBJECTIVETo investigate the efficacy and toxicity of methotrexate (MTX) give intravenously in the primary treatment of gestational trophoblastic tumor (GTT).

METHODSA total of 37 patients with low-risk GTT was primarily treated by single MTX in Women's Hospital, School of Medicine, Zhejiang University. Data on the patients' age, clinical stage, WHO classification criteria, antecedent pregnancy, presenting level of human chorionic gonadotropin, courses of chemotherapy required to achieve complete remission, and toxicity related to chemotherapy treatments were collected.

RESULTSThirty-seven patients with low-risk GTT totally received 137 cycles of MTX between Oct. 1999 and Sep. 2002, 34 patients (91.9%) achieved complete remission. Twenty-nine patients received multiple courses of MTX, complete remission was induced in 26 patients (89.7%). The complete response rates of I stage and III stage were 100.0% and 70.0% (P = 0.03) respectively in patients who were received multiple courses of MTX. However, eight patients received single course of chemotherapy, 7 patients achieved complete remission, and 1 achieved complete remission after another additional course of MTX was conducted. Grade III side effects (WHO criteria) only appeared in 7 courses (5.1%) during MTX treatment. Follow-up data showed that only one patient with single course of chemotherapy relapsed after 6 months.

CONCLUSIONSingle MTX chemotherapy may be effective and well tolerated for low-risk GTT.

Adolescent ; Adult ; Antimetabolites, Antineoplastic ; administration & dosage ; Choriocarcinoma ; drug therapy ; Drug Administration Schedule ; Female ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Methotrexate ; administration & dosage ; Pregnancy ; Uterine Neoplasms ; drug therapy

OBJECTIVETo evaluate the clinical effect and safety of combined use of methotrexate and mifepristone for treatment of ectopic pregnancy.

METHODSBy searching in the major databases of CNKI, CBMdisk and Pubmed according to the criteria of evidence-based medicine, we collected data of randomized controlled trials pertaining to combined use of methotrexate and mifepristone in the treatment of ectopic pregnancy.

RESULTSTwenty-three randomized controlled trials involving totally 1 706 patients were collected according to the inclusion criteria, and meta-analysis of the data indicated that combined use of methotrexate and mifepristone can be of great value in the management of ectopic pregnancy in comparison with exclusive use of methotrexate [ combined odds ratio (OR) was 2.84 with 95%confidence interval [CI] (2.18, 3.69), Z=7.79, P<0.000 01].

CONCLUSIONThe clinical evidence derived from the analysis suggests that the combination of methotrexate and mifepristone for ectopic pregnancy management can be effective with good safety security and minimal side effects, but still, this conclusion needs further verification by randomized, double-blind, and controlled trials with larger sample size and more rigorous trial design.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; Abortifacient Agents, Steroidal ; administration & dosage ; Adult ; Drug Therapy, Combination ; Female ; Humans ; Methotrexate ; administration & dosage ; Mifepristone ; administration & dosage ; Pregnancy ; Pregnancy, Ectopic ; drug therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome

OBJECTIVETo select a safe, quick and effective method for terminating ectopic pregnancy (EP) with few adverse effects.

METHODSPatients were divided into 2 groups. The observed group was treated with methotrexate (MTX, 50 mg/m2 for single dose intramuscular injection) plus RU 486 (600 mg taken orally in the morning with empty stomach, followed with fasting for 2 hrs) and Waiyun Zhuyu decoction (WZD, one dose a day for 7-10 days). The control group was only treated with MTX, with the same regimen as used in the observed group.

RESULTSThe curative rate, time for blood beta-HCG recovering, lump absorption time, and tube recanalization rate in the observed group were better than those in the control group (P < 0.01). CONCLUSION; The key links for successfully treating EP with conservative drug therpy are to diagnose the disease early and clearly, and to select indicative subject strictly. The scheme of single dose administration of MTX plus RU486 combined with WZD, with its high efficacy and few adverse reaction, may be used as the first choice for referential clinical drugs administration.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Methotrexate ; administration & dosage ; Mifepristone ; administration & dosage ; Phytotherapy ; Pregnancy ; Pregnancy, Ectopic ; drug therapy ; Retrospective Studies ; Treatment Outcome

AIMTo prepare the micelles of stearic acid-grafted chitosan oligosaccharide and investigate the drug release from micelles.

METHODSMediated by a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), stearic acid (SA) was covalently attached to chitosan oligosaccharide (CSO), and the graft polymer (CSO-SA) was obtained. The critical aggregation concentration (CAC) of the CSO-SA was determined by measuring the fluorescence intensity of pyrene as a fluorescent probe. The effect of various pH dispersed media and concentration of tripolyphosphate sodium (TPP) on the micellar size distribution and zeta-potential measured by light scattering and electrophoretic mobility, was investigated. In buffers of different pH, the release profiles of methotrexate (MTX) from micelles were evaluated.

RESULTSThe CAC value of CSO-SA in deionized water was 0.05 g x L(-1). The mean diameter of CSO-SA micelles was 26.7 nm and the zeta potential was (55.9 +/- 0.1) mV. With the increase of TPP concentration, the size and MTX encapsulation of CSO-SA micelles increased, while the zeta-potential decreased. With the decrease of pH value of dispersed media, the size and zeta-potential of CSO-SA micelles increased, and the MTX encapsulation in CSO-SA micelles decreased. While the enhancement of drug release from the micelles was observed.

CONCLUSIONThe graft polymer of CSO-SA provides polymeric micelles, which possessed a low CAC value in aqueous media. The drug release in vitro from CSO-SA micelles was affected by the pH of delivery media.

Chitosan ; administration & dosage ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Hydrogen-Ion Concentration ; Methotrexate ; administration & dosage ; chemistry ; Micelles ; Oligosaccharides ; administration & dosage ; chemistry ; Particle Size ; Polymers ; Polyphosphates ; Solubility ; Stearic Acids ; administration & dosage ; chemistry