OBJECTIVETo evaluate the sensitivity of NT-pro-BNP in daunorubicin (DNR) induced myocardial damage by monitoring the level of NT-pro-BNP and myocardial enzymes (CK, CKMB) before and after DNR treatment in childhood acute leukemia (AL) and performing control study.

METHODSSixty-two cases (total 194 samples) which diagnosed as primary AL were enrolled and had received the conventional chemotherapy. According to the cumulative dose of DNR, they were divided into three groups: cumulative dose ≤ 60 mg/m(2) (group A); cumulative dose 60 - 120 mg/m(2) (group B); cumulative dose > 120 mg/m(2) (group C) and 15 cases with idarubicin (IDA) or mitoxantrone (MXR) as altervative to DNR (group D).

RESULTSThere was a significant difference (P = 0.000) in the level of NT-pro-BNP before and after DNR therapy, but did not in the myocardial enzymes activities (CK, P = 0.085 and CKMB, P = 0.076). The level of NT-pro-BNP appeared obviously elevated (P = 0.001) when DNR cumulative dose > 60 mg/m(2). While the level of CKMB did (P = 0.022) until DNR cumulative dose > 120 mg/m(2). In the 15 cases used IDA or MXR as alternative to DNR, the level of NT-pro-BNP fall from (239.9 ± 230.0) ng/L to (137.0 ± 131.9) ng/L (P = 0.024).

CONCLUSION(1) Compared with myocardial enzymes detection, NT-pro-BNP level can predict earlier DNR-induced cardiotoxicity. (2) Selection of the second or third generation anthracycline to treat AL can significantly reduce the cardiotoxicity in children.

Anthracyclines ; Cardiotoxicity ; Daunorubicin ; administration & dosage ; Humans ; Idarubicin ; administration & dosage ; Leukemia ; drug therapy

OBJECTIVETo compare the effectiveness and side effects of two chemotherapy regimens [pirarubicin + cytarabine (TA) and daunorubicin + cytarabine (DA)] in patients with acute myeloid leukemia (AML).

METHODSFrom Oct 2006 to Jul 2009, there were 207 newly diagnosed AML patients randomized into DA or TA group from 72 centers all over the country. The aim of this clinical trial is to observe and evaluate complete remission rate (CR), total remission rate (TRR), and side effect after one or two circles of therapy.

RESULTSIn 198 evaluable patients, 126 cases in TA group and 72 in DA group were evalvable, with a ratio of 1.75:1. CR was 69.8% and TRR (CR + PR) was 81.8% in TA group and 63.9%, 80.9% in DA group, correspondingly (P > 0.05). For patients with subtype M(2), CR (77.1%) in TA group was higher than that in DA (60%). There was no difference in side effect between the two groups.

CONCLUSIONThere is no difference of the effect between TA and DA chemotherapy for newly diagnosed AML patients. But for subtype M(2), TA is more efficacy. And there is no difference in side effect between the two regimens.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Prospective Studies

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Young Adult

AIMTo study the pharmaceutical characterization and pharmacokinetics of long-circulating liposomes containing daunorubicin.

METHODSThe morphology of daunorubicin long-circulating liposome was surveyed under the transmission electron microscope. The size of daunorubicin long-circulating liposomes was determined by laser scatter method. The entrapment efficiency and accelerative experiment stability of the daunorubicin long-circulating liposomes were examined. Visible spectrophotometry and the HPLC method were established for determination of the daunorubicin in the long-circulating liposomes. The percent release of daunorubicin from long-circulating liposomes in HBS (pH 7.5) and rat serum at 37 degrees C were examined. The pharmacokinetics in rats were studied.

RESULTSThe high entrapment efficiency (> 85%) and stabilized long-circulating liposomes could be achieved. The drug was slowly released from the daunorubicin long-circulating liposomes. The drug released from liposomes was less than 10% in 24 h. The T1/2 alpha and AUC of long-circulating liposome were higher than those in injections.

CONCLUSIONThe long-circulating liposomes prepared by us have high encapsulation efficiency and the pharmaceutical characterization showed good stability, they can be used for clinical purpose.

Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Daunorubicin ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; Liposomes ; Male ; Phosphatidylethanolamines ; Polyethylene Glycols ; chemistry ; Random Allocation ; Rats ; Rats, Wistar

Azacitidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; Daunorubicin ; administration & dosage ; pharmacology ; HL-60 Cells ; Humans ; PTEN Phosphohydrolase ; metabolism

OBJECTIVETo observe the efficacy and side effect of DA/HA regimen chemotherapy for the treatment of refractory and relapsed paroxysmal nocturnal hemoglobinuria (PNH).

METHODSEight patients with refractory and relapsed PNH were treated with DA/HA regimen chemotherapy. Three patients were treated with DA (DNR 40 mg/d, i.v.drip, the first and the second day; 20 mg/d, i.v.drip, the third day; Ara-C 100 mg/d, i.v.drip, for 5 days) and 5 patients with HA (HHT 2 - 3 mg/d, i.v.drip, for 5 days; Ara-C 100 mg/d, i.v.drip, for 5 days).

RESULTSAll the 8 patients responded well: the PNH clone was diminished in five patients. Hemolysis was remitted in 6 cases. Five patients showed improvement in hematological parameters. The dosage of corticosteroid was decreased in all of them. No serious side effect was revealed.

CONCLUSIONDA/HA regimen chemotherapy was safe and effective for refractory and relapsed PNH patients.

Adolescent ; Adult ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Drug Therapy, Combination ; Female ; Glycosylphosphatidylinositols ; analysis ; Harringtonines ; Hemoglobinuria, Paroxysmal ; drug therapy ; Humans ; Male

OBJECTIVETo evaluate the effectiveness of AML-XH-99-M3 protocol for treatment of acute promyelocytic leukemia (APL) in children.

METHODSThirty-three children with APL received AML-XH-99-M3 protocol treatment. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were evaluated by the Kaplan-Meier medthod with SPSS13.0 software.

RESULTSThirty patients (90.9%) achieved a complete remission (CR) after one course of treatment. The total CR rate was 100%. Six patients (18.2%) relapsed in an average of 29.17 months (16-38 months). Two patients (6.1%) died. The 7-year EFS and DFS in the 30 patients were 73.4+/-9.4%. The overall survival rate was 91.2+/-6.0%. The difference of EFS was observed in patients receiving intermittent all-trans-retinoic acid (ATRA) administration or not in the maintenance therapy (88.9+/-10.5% vs 62.5+/-13.6%) (P<0.05).

CONCLUSIONSThe AML-XH-99-M3 protocol for the treatment of APL produced a higher CR rate and higher EFS, DFS and OS rates in children. Intermittent administration of ATRA in the maintenance therapy can improve EFS rate.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Humans ; Infant ; Leukemia, Promyelocytic, Acute ; drug therapy ; mortality ; Male ; Tretinoin ; administration & dosage

We analyzed the efficacy and toxicity of a modified Cancer and Leukemia Group B (CALGB) 19802 regimen in adult acute lymphoblastic leukemia (ALL). From February 2002 to August 2005, 25 adults with untreated ALL were enrolled in the study. Compared to the original regimen, the modified CALGB 19802 regimen consisted of a 4-drug induction (cyclophosphamide, daunorubicin, vincristine, and prednisone) instead of a 5-drug induction (L-asparaginase was added to the previous regimen). This was followed by high-dose methotrexate (1,000 mg/m(2)X3 days) and cytarabine (2,000 mg/m(2)X4 days) for the consolidation cycles. High-dose systemic and intrathecal methotrexate was given for central nervous system prophylaxis. Twentythree patients (92%) achieved a complete remission (CR), and two patients (8%) had refractory disease. With a median follow-up of 21.5 months, 10 patients (40%) were alive and continued to be in CR. The 3-yr probability of an event-free survival and the overall survival were 39.0% and 47.4%, respectively. Treatment related mortality and major grade 3 to 4 neurotoxicity occurred in 1 patient and 3 patients, respectively. The modified CALGB 19802 regimen demonstrated a high remission rate and a favorable survival rate.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cyclophosphamide/*administration & dosage ; Daunorubicin/*administration & dosage ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy ; Prednisone/*administration & dosage ; Remission Induction ; Treatment Outcome ; Vincristine/*administration & dosage

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7–2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.
Absorption ; Administration, Oral ; Animals ; Biological Availability ; Breast Neoplasms ; Carcinoma, Non-Small-Cell Lung ; Cell Line ; Daunorubicin ; In Vitro Techniques ; Ovarian Neoplasms ; P-Glycoprotein ; Paclitaxel* ; Pharmacokinetics ; Plasma ; Rats* ; Verapamil

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Female ; Humans ; Idarubicin ; administration & dosage ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Young Adult