-
Archives of Internal Medicine Jul 2010Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. We evaluated the prevalence and determinants of left ventricular (LV) dysfunction in...
BACKGROUND
Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. We evaluated the prevalence and determinants of left ventricular (LV) dysfunction in a large cohort of long-term CCSs treated with different potentially cardiotoxic therapies.
METHODS
The study cohort consisted of all adult 5-year CCSs who were treated with potentially cardiotoxic therapies and who visited our late effects outpatient clinic. Echocardiography was performed in patients who had received anthracyclines, cardiac irradiation, high-dose cyclophosphamide, or high-dose ifosfamide. Detailed treatment data were registered. Both multivariate linear and logistic regression analyses were performed.
RESULTS
Of 601 eligible CCSs, 525 (87%) had an echocardiogram performed, of which 514 were evaluable for assessment of the LV shortening fraction (LVSF). The median overall LVSF in the whole group of CCSs was 33.1% (range, 13.0%-56.0%). Subclinical cardiac dysfunction (LVSF <30%) was identified in 139 patients (27%). In a multivariate linear regression model, LVSF was reduced with younger age at diagnosis, higher cumulative anthracycline dose, and radiation to the thorax. High-dose cyclophosphamide and ifosfamide were not associated with a reduction of LVSF. Vincristine sulfate was associated with a nonsignificant decrease of cardiac function (P = .07). Epirubicin hydrochloride was as cardiotoxic as doxorubicin when corrected for tumor efficacy, and daunorubicin hydrochloride seemed less cardiotoxic.
CONCLUSIONS
A high percentage (27%) of young adult CCSs have an abnormal cardiac function. The strongest predictors of subclinical cardiac dysfunction are anthracycline dose, cardiac irradiation, and younger age at diagnosis. There is a suggestion that daunorubicin is less cardiotoxic than other anthracyclines.
Topics: Adolescent; Adult; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cohort Studies; Doxorubicin; Echocardiography; Epirubicin; Female; Follow-Up Studies; Humans; Infant; Linear Models; Logistic Models; Male; Multivariate Analysis; Neoplasms; Netherlands; Prevalence; Prospective Studies; Risk Factors; Ventricular Dysfunction, Left
PubMed: 20660845
DOI: 10.1001/archinternmed.2010.233 -
Journal of Pharmaceutical Sciences Oct 1981A fast and sensitive high-pressure liquid chromatographic method was developed for the quantitation of doxorubicin, daunorubicin, and their aglycones in pharmaceutical...
A fast and sensitive high-pressure liquid chromatographic method was developed for the quantitation of doxorubicin, daunorubicin, and their aglycones in pharmaceutical preparations. Because its higher pH extends column life while permitting determination of impurities, this system represents an improvement over previously published methods. It utilizes a C18 bonded silica gel column and a solvent system consisting of methanol-0.01 M monobasic ammonium phosphate aqueous solution (65:35) at pH 4.0 and 1600 psi of pressure. The accuracy of the doxorubicin and daunorubicin determinations, expressed as the coefficient of variation, is 1.65 and 1.27% respectively. The aglycones can be determined with a precision of less than 1.3%.
Topics: Chromatography, High Pressure Liquid; Daunorubicin; Doxorubicin; Drug Contamination
PubMed: 7299643
DOI: 10.1002/jps.2600701006 -
Clinical Pharmacology and Therapeutics Jan 1977In 38 adriamycin experiments and 4 daunorubicin experiments, radioimmunoassay readily and reproducibly detects and estimates these drugs and immunologically similar... (Comparative Study)
Comparative Study
In 38 adriamycin experiments and 4 daunorubicin experiments, radioimmunoassay readily and reproducibly detects and estimates these drugs and immunologically similar metabolites in patients' plasma and urine to at least 120 hr after dosing without interference by concurrent medication. The plasma drug decay follows first-order kinetics in a triphasic pattern. Radioimmunoassay and fluorescence assay show similar decay up to 4 hr but diverge at that point with the fluorescence assay yielding higher values. Pharmocokinetic differences are amplified in patients with liver dysfunction and may be caused by fluorescent drug metabolites not sensitive to radioimmunoassay or nonspecific fluorescent materials. The radioimmunoassay offers the capability to measure adriamycin and daunorubicin in clinical settings in which fluorescence assay is not available.
Topics: Daunorubicin; Doxorubicin; Fluorometry; Humans; Kinetics; Methods; Neoplasms; Radioimmunoassay; Time Factors
PubMed: 832449
DOI: 10.1002/cpt197721170 -
International Journal of Hematology Jul 1999A prospective randomized study was conducted to compare the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myelogenous leukemia... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
A prospective randomized trial of KRN8602 and cytosine arabinoside vs. daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. The KRN8602 Leukemia Study Group.
A prospective randomized study was conducted to compare the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myelogenous leukemia (AML). Fifty-eight patients were randomized and received induction therapy consisting of cytosine arabinoside (AraC) 100 mg/m2/day for 7 days combined with either KRN8602 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride [KRN]) 15 mg/m2/day for 5 days (KRN/AraC group) or daunorubicin (DNR) 40 mg/m2/day for 3 days (DNR/AraC group). Complete remission rate was 78.6% (22/28) in the KRN/AraC group and 73.1% (19/26) in the DNR/AraC group. There was a higher incidence of nausea/vomiting and anorexia observed in the KRN/AraC group compared to the DNR/AraC group, while the incidence of other adverse effects (stomatitis, diarrhea, and infectious complications) were similar between both groups. No electrocardiogram (ECG) abnormalities were observed after treatment in the KRN/AraC group, while in the DNR/AraC group, one patient showed ECG abnormality and three patients exhibited either arrhythmia, heart failure, or tachycardia. Mental disorder was reported in two cases in the KRN/AraC group. These findings suggest that KRN/AraC is similar in effectiveness to DNA/AraC but more toxic in central nervous system and gastrointestinal symptoms and less toxic regarding cardiac function in patients with previously untreated AML.
Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carubicin; Central Nervous System Diseases; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Prospective Studies; Treatment Outcome
PubMed: 10446490
DOI: No ID Found -
Archives of Toxicology 1996The effect of repeated i.v. administration (once weekly, 12 administrations) of a new antineoplastic agent, Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,... (Comparative Study)
Comparative Study
The effect of repeated i.v. administration (once weekly, 12 administrations) of a new antineoplastic agent, Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5, 11-dioxo-5,6-dihydro-11 H-indeno [1,2-c]-isochinoline hydrochloride, 10 mg/kg) and daunorubicin (3 mg/kg) were investigated in rabbits in vivo. The criterion of occurrence of cardiotoxicity was compared with a control group of animals. Noninvasive polygraphic records were used to evaluate the function of the heart. The morphological changes of the heart were evaluated after the death of animals. There were no significant changes found in the ratio of the pre-ejection period/left ventricular ejection time (PEP: LVET ratio) after administration of Oracin (values between 0.3080 and 0.3310) or in the control group (values between 0.3425 and 0.3885). The administration of daunorubicin induced a significant, progressive increase in the PEP: LVET ratio (0.3775-0.9473), which was significantly different both from the Oracin-treated and the control group of animals. Histological examination of the hearts from the control group revealed normal structure of the myocardium including minute changes (dispersed cardiomyocytes with intensively eosinophilic cytoplasm, and several single cells with degenerated myofibrils) similar to the normal changes in muscle tissue. A very similar scenario was found in the Oracin group with the exception of one case where a slightly higher number of degenerated and necrotic cells was occurring. Administration of daunorubicin resulted in severe dispersed damage of the myocardium (myocytolysis with subsequent interstitial fibrosis), the changes being markedly different from those of the Oracin treatment and the control group. On the basis of our results it is possible to conclude that the administration of Oracin (10 mg/kg i.v.) did not induce signs of cardiotoxicity in rabbits in vivo.
Topics: Animals; Antineoplastic Agents; Daunorubicin; Ethanolamines; Heart; Isoquinolines; Male; Rabbits
PubMed: 8870958
DOI: 10.1007/s002040050324 -
The Journal of Antibiotics Sep 1985By using a strain of Streptomyces willmorii, daunorubicin (daunomycin) was stereoselectively converted into N-acetyl-13(S)-dihydrodaunomycin and...
By using a strain of Streptomyces willmorii, daunorubicin (daunomycin) was stereoselectively converted into N-acetyl-13(S)-dihydrodaunomycin and bisanhydro-13-dihydrodaunomycinone. The absolute stereochemistry of the new chiral center in N-acetyl-13(S)-dihydrodaunomycin was established by means of nuclear Overhauser effect measured in the 9,13-O-isopropylidene derivative.
Topics: Daunorubicin; Fermentation; Molecular Conformation; Naphthacenes; Streptomyces
PubMed: 4066504
DOI: 10.7164/antibiotics.38.1219 -
Lloydia 1977
Topics: Binding Sites; DNA; Daunorubicin; Doxorubicin; Molecular Conformation; Neoplasms; Neoplasms, Experimental; Structure-Activity Relationship
PubMed: 875639
DOI: No ID Found -
Cancer Chemotherapy and Pharmacology 1979We have compared the toxicologic, pharmacologic, and therapeutic properties of the DNA complexes of daunorubicin and doxorubicin, after intravenous (IV) administration... (Comparative Study)
Comparative Study
We have compared the toxicologic, pharmacologic, and therapeutic properties of the DNA complexes of daunorubicin and doxorubicin, after intravenous (IV) administration into mice. The overall toxicity of doxorubicin is significantly reduced after IV injection as a DNA complex while daunorubicin-DNA is as toxic as free daunorubicin. On hemopoietic stem cells, daunorubicin-DNA was found to be more cytotoxic than daunorubicin, while the opposite was observed with doxorubicin and doxorubicin-DNA. Both complexes are more effective than the corresponding free drugs on the L1210 murine leukemia, when given IV at equitoxic doses. The tissue uptake in mice, after IV administration, is generally lower when the drugs are given bound to DNA. The stability of the two DNA complexes is very different in the bloodstream: daunorubicin-DNA behaves more like a prodrug of daunorubicin, while doxorubicin-DNA, remaining stable in the bloodstream, meets much more the requirements of an ideal drug-macromoleculare carrier entity.
Topics: Animals; Bone Diseases; DNA; Daunorubicin; Doxorubicin; Female; Lethal Dose 50; Leukemia L1210; Mice; Tissue Distribution
PubMed: 498415
DOI: 10.1007/BF00253101 -
Medical and Pediatric Oncology 1985Fourteen patients with advanced measurable colorectal cancer were treated with daunorubicin hydrochloride (DNR). The drug was administered at a dose of 15 mg/m2 on day 1...
Fourteen patients with advanced measurable colorectal cancer were treated with daunorubicin hydrochloride (DNR). The drug was administered at a dose of 15 mg/m2 on day 1 through 3 and 8 through 10. After a 4-day rest period DNR was given in weekly injections of 15 mg/m2. There were no partial or complete responses. This study failed to confirm the previously reported therapeutic activity of this agent in colorectal carcinoma, using an identical dose and schedule. We have initiated a phase 1 study of daunorubicin to identify a maximum tolerated dose using an every 3-week schedule for future phase II trials in solid tumors.
Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Daunorubicin; Drug Evaluation; Female; Humans; Male; Middle Aged; Rectal Neoplasms; Time Factors
PubMed: 3969059
DOI: 10.1002/mpo.2950130107 -
Cancer Treatment Reports May 1979One hundred and thirty-three patients, 94 with acute luekemia and 39 with solid tumors, received rubidazone, alone or in combination, at M. D. Anderson Hospital. The...
One hundred and thirty-three patients, 94 with acute luekemia and 39 with solid tumors, received rubidazone, alone or in combination, at M. D. Anderson Hospital. The initial study, a phase I--II study carried out in 39 patients with acute leukemia, revealed substantial antileukemic activity with optimal results at a dose level of 450 mg/m2. Toxic manifestations included an acute reaction suggestive of histamine release with dose-limiting mucositis at a dose of 600 mg/m2. Forty-seven patients with acute leukemia were treated at phase II dose levels. Thirteen of 32 patients (42%) with acute myelogenous leukemia and seven of ten patients (70%) with acute lymphocytic leukemia achieved complete remission. Twenty-seven previously untreated patients with acute leukemia who were greater than 50 years old were treated with rubidazone in combination with cytosine arabinoside, vincristine, and prednisone. Fifteen patients (50%) achieved complete remission including 12 of 15 patients (73%) who were treated at a dose of 200 mg/m2 of rubidazone on Day 1 and a dose of 70 mg/m2/day X 7 days of cytosine arabinoside (continuous infusion). For patients with solid tumors, the dose-limiting toxic effect was myelosuppression at a dose of 200 mg/m2. Other toxicity at that dose level was minimal. The best responses were seen in patients with carcinoma of the period with two of four evaluable patients showing objective tumor regression. Of six previously untreated patients with thyroid carcinoma none responded, and in a phase II study of patients with breast cancer there were no partial remissions among 13 patients. Cardiac toxicity, manifested by congestive heart failure, occurred in seven patients at cumulative doses of 1050--2600 mg/m2 of rubidazone; all patients had had prior anthracycline therapy at low doses. Rubidazone has been shown to be an active antileukemic agent, but appears to be less active than Adriamycin in our studies of patients with solid tumors.
Topics: Acute Disease; Adult; Breast Neoplasms; Daunorubicin; Drug Evaluation; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Male
PubMed: 287557
DOI: No ID Found