aclarubicin and Leukemia

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Clinical Trials as Topic; Heart; Humans; Leukemia; Naphthacenes

Topics: Aclarubicin; Anthraquinones; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Cell Survival; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Heart; Humans; Idarubicin; Leukemia; Menogaril; Mitoxantrone; Naphthacenes; Nogalamycin; Sarcoma; Structure-Activity Relationship

Aclacinomycin A (aclarubicin; ACM) is a new class II anthracycline antibiotic. Preclinical studies suggested that ACM had approximately equivalent antitumour activity but produced substantially less cardiotoxicity compared to other anthracyclines. Because of the recognized importance of these compounds in the treatment of haematological tumours, clinical trials of ACM were initiated in the late 1970s. ACM has been extensively evaluated in patients with relapsed leukaemia and advanced malignant lymphoma. Analysis of results compiled from Europe, Japan, and the United States shows that ACM is probably equivalent to doxorubicin for remission induction of patients with relapsed acute non-lymphoblastic leukaemia. Initial studies using ACM alone and in combination with standard cytotoxic drugs in previously untreated patients compare favourably with the best standard treatment for this disease. The antitumour activity of ACM in patients with acute lymphoblastic leukaemia or malignant lymphoma who have previously received doxorubicin or daunorubicin is low, and the issue of whether ACM lacks clinical cross-resistance to other anthracyclines is unresolved. Acute cardiac arrhythmias have been observed following administration of ACM, but congestive cardiomyopathy has been uncommon. Results to date all indicate that ACM has fulfilled its early expectations of antileukaemic activity and reduced toxicity. These hypotheses should now be evaluated in prospective, randomized trials with conventional anthracyclines.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance; Heart; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Naphthacenes

Topics: Aclarubicin; Acute Disease; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Clinical Trials as Topic; Cytarabine; Doxorubicin; Humans; Interferon Type I; Leukemia; Middle Aged; Naphthacenes

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Age Factors; Aminoacridines; Amsacrine; Anthraquinones; Antibodies, Monoclonal; Azacitidine; Bone Marrow Transplantation; Child; Child, Preschool; Drug Administration Schedule; Etoposide; Humans; Ifosfamide; Immunotherapy; Infant; Interferons; Leukemia; Leukemia, Lymphoid; Liposomes; Middle Aged; Mitoxantrone; Naphthacenes; Prognosis; Teniposide; Transplantation, Homologous; Transplantation, Isogeneic; Vinblastine; Vindesine

Topics: Aclarubicin; Acute Disease; Alkylating Agents; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cell Transformation, Neoplastic; DNA; Leukemia; Naphthacenes; Purine Nucleotides; Pyrimidine Nucleotides

Topics: Aclarubicin; Acute Disease; Adult; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cells, Cultured; Child; Cytarabine; Deoxycytidine Monophosphate; Drug Therapy, Combination; Humans; Kinetics; Leukemia; Leukemia L1210; Leukocytes; Naphthacenes

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Female; Glycosides; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphoma; Naphthacenes; Ovarian Neoplasms; Sarcoma

The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting.

Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Cytarabine; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction

Topics: Aclarubicin; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Child; Clinical Protocols; Clinical Trials as Topic; Female; Humans; Leukemia; Male

Topics: Aclarubicin; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Female; Hematuria; Humans; Infant; Leukemia; Lymphoma; Male; Multicenter Studies as Topic; Retrospective Studies

Aclacinomycin A (ACM) is a new anthracycline antibiotic, isolated from Streptomyces galilaeus. This agent is presenting major chemical differences from the conventional anthracycline DNR and ADM, as a class II anthracyclines which inhibit more RNA than DNA. In clinical studies, good CR responses ranging about 30% in AML patients depend upon their background. Toxicities consisted of mainly upper GI tract and bone marrow. Cardiac toxicities, especially late cumulative effects are not reported. Some responses noted in malignant lymphomas and breast carcinoma, but needed further studies, including possibility of cross resistance and differentiation effects.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Bone Marrow; Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Leukemia; Middle Aged; Naphthacenes; Remission Induction

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Clinical Trials as Topic; Heart; Humans; Leukemia; Naphthacenes

Aclacinomycin A (aclarubicin; ACM) is a new class II anthracycline antibiotic. Preclinical studies suggested that ACM had approximately equivalent antitumour activity but produced substantially less cardiotoxicity compared to other anthracyclines. Because of the recognized importance of these compounds in the treatment of haematological tumours, clinical trials of ACM were initiated in the late 1970s. ACM has been extensively evaluated in patients with relapsed leukaemia and advanced malignant lymphoma. Analysis of results compiled from Europe, Japan, and the United States shows that ACM is probably equivalent to doxorubicin for remission induction of patients with relapsed acute non-lymphoblastic leukaemia. Initial studies using ACM alone and in combination with standard cytotoxic drugs in previously untreated patients compare favourably with the best standard treatment for this disease. The antitumour activity of ACM in patients with acute lymphoblastic leukaemia or malignant lymphoma who have previously received doxorubicin or daunorubicin is low, and the issue of whether ACM lacks clinical cross-resistance to other anthracyclines is unresolved. Acute cardiac arrhythmias have been observed following administration of ACM, but congestive cardiomyopathy has been uncommon. Results to date all indicate that ACM has fulfilled its early expectations of antileukaemic activity and reduced toxicity. These hypotheses should now be evaluated in prospective, randomized trials with conventional anthracyclines.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance; Heart; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Naphthacenes

We have recently performed a prognostic investigation of a randomized controlled trial with bestatin for acute non-lymphocytic leukemia in adults. Out of 115 patients registered in this study, 101 patients (48 in a bestatin group and 53 in a control group) were evaluated as eligible. The 50% remission duration was 20.4 months for the bestatin group compared with 11.3 months for the control group. Long-term remission rate at 4 years was 36.5% for the bestatin group compared with 24.1% for the control group, and their respective 50% survival time were 33.0 and 18.1 months, while the long-term survival rate at 4 years was 46.0% for the bestatin group compared with 25.5% for the control group. The bestatin group had a longer remission duration and survival time than the control group. The remission duration and survival time in patients under 49 years of age were not different between the groups. However, in patients over 50 years of age, the bestatin group had a significantly longer remission duration and survival time than the control group. Side effects of bestatin were mild and transient. These data suggest the usefulness of bestatin for the treatment of adult acute nonlymphocytic leukemia.

Topics: Aclarubicin; Acute Disease; Adjuvants, Immunologic; Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Follow-Up Studies; Humans; Leucine; Leukemia; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone; Prognosis; Random Allocation

Topics: Aclarubicin; Acute Disease; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Clinical Trials as Topic; Cytarabine; Doxorubicin; Humans; Interferon Type I; Leukemia; Middle Aged; Naphthacenes

Topics: Aclarubicin; Adolescent; Adult; Aged; Animals; Antibiotics, Antineoplastic; Clinical Trials as Topic; Cytarabine; Humans; Leukemia; Mice; Middle Aged; Naphthacenes

Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML. However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain unclear. In this study, SKNO-1 and Kasumi-1 cells with t(8;21) were used. Compared with individual or pairwise administration of homoharringtonine, aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and induction of apoptosis in SKNO-1 and Kasumi-1 cells. HAA caused cleavage of the AML1-ETO (AE) oncoprotein to form truncated AE (ΔAE). Pretreatment with the caspase-3 inhibitor caspase-3 inhibitor Q-DEVD-OPh (QDO) not only suppressed HAA-induced apoptosis but also abrogated the cleavage of AE and generation of ΔAE. These results suggest that HAA synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein, thus providing direct evidence for the strong activity of HAA toward t(8;21) AML.

Topics: Aclarubicin; Antineoplastic Agents; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Proliferation; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 8; Core Binding Factor Alpha 2 Subunit; Cytarabine; Drug Synergism; Harringtonines; Homoharringtonine; Humans; Leukemia; Oncogene Proteins, Fusion; Proteolysis; RUNX1 Translocation Partner 1 Protein; Translocation, Genetic

To explore the sensitivity of survivin-positive primary acute leukemia (AL) cells to various chemotherapeutics, RT-PCR was used to detect the expression of survivin mRNA in AL cells, the cytotoxicity of chemotherapeutics was investigated with the MTT assay. The results indicated that for the primary AL cells cultured with various chemotherapeutics for 15 hours, the cytotoxicities of daunorubicin (DNR), homoharringtonine (HHT), aclacinomycin (Acla), Ara C (cytosine arabinoside), HA (HHT + Ara C), DA (DNR+Ara C) to the survivin-positive AL cells were similar with that to the survivin-negative AL cells. When AL cells were treated with AA (Acla + Ara C) in vitro, the cytotoxicity in survivin-positive group was apparently higher than that in survivin-negative group [(37.24 +/- 18.36)% vs (24.32 +/- 9.33)%, P = 0.032]. It is suggested that the survivin-positive AL cells may be sensitive to some chemotherapy, such as AA (Acla + Ara C).

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Antineoplastic Agents; Cell Survival; Cytarabine; Drug Screening Assays, Antitumor; Female; Gene Expression Regulation, Neoplastic; Humans; Inhibitor of Apoptosis Proteins; Leukemia; Male; Microtubule-Associated Proteins; Middle Aged; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survivin; Tumor Cells, Cultured

Aclarubicin (ACLA), which belongs to the antracycline class of antineoplasic agents, has been demonstrated as a differentiating agent for a broad range of human solid tumors and leukemia. By using dihydroethidium as a fluorescent probe, we show the ability of subtoxic (i.e. differentiating) concentration of ACLA to generate reactive oxygen species in both K562 and HL-60 leukemia cell lines. Besides, we have used a calcein-based spectrofluorimetric assay to determine the influence of ACLA treatment on the cellular labile iron pool (LIP). In both cell lines, the LIP level was markedly decreased in the presence of ACLA. Nevertheless, whereas ACLA-induced differentiation was obviously ROS-dependent, the LIP decrease was rather ROS-independent.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Cell Differentiation; Fluorescent Dyes; Free Radicals; HL-60 Cells; Humans; Iron; K562 Cells; Leukemia; Reactive Oxygen Species

We investigated the mode of cell death induced by the anthracyclines, aclarubicin, doxorubicin and daunorubicin in the human leukemia cell lines, HL60 and Jurkat. The cells were incubated with drug concentrations up to 500 nM for periods between 3 and 24 hours, followed by morphological and biochemical analyses. All three substances induced DNA fragmentation, evident as DNA laddering and appearance of cells with hypodiploid DNA content, externalization of phosphatidyl serine, activation of caspases and degradation of the apoptosis-specific endonuclease inhibitor DFF45. However, concentrations and times necessary for these effects to occur were different, aclarubicin being the quickest acting drug with a lag phase of 3 h, followed by daunorubicin with 6 h and doxorubicin with 24 h. More importantly, aclarubicin induced these effects while the cell membrane was intact, whereas doxorubicin and daunorubicin led to immediate loss of membrane integrity. Programmed cell death is characterised by preservation of membrane integrity in order to allow removal of apoptotic bodies, whereas cell rupture is an early event in necrosis. We therefore suggest that, in our experimental settings, doxorubicin- and daunorubicin-induced cell death occurs by necrosis, while aclarubicin induces programmed cell death.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Apoptosis; Apoptosis Regulatory Proteins; Caspases; Cell Death; Cell Membrane; Daunorubicin; DNA Fragmentation; Doxorubicin; Enzyme Activation; HL-60 Cells; Humans; Jurkat Cells; Leukemia; Models, Biological; Necrosis; Phosphatidylserines; Proteins

Anthracycline antitumor drugs induce erythroid differentiation of the K562 erythroleukemic cell line at subtoxic concentrations. Aclacinomycin (ACM) stimulates this process by activating the erythroid transcription factor GATA-1, that controls genes involved in hemoglobin biosynthesis. To investigate the implication of GATA-1 in this process, we used a specific anti-GATA-1 polyclonal antibody that we produced in our laboratory. The GATA-1 transcription factor was then monitored during erythroid differentiation induced by aclacinomycin. Here we show that a cellular redistribution and a modification of the phosphorylation state of this transcription factor occurred during ACM-mediated cell differentiation. It suggests that anthracyclines can induce the erythroid differentiation of neoplastic cells by activating the transcription factor GATA-1, probably via its clustering into nuclear foci.

Topics: Aclarubicin; Adjuvants, Immunologic; Antibody Specificity; Cell Compartmentation; Cell Nucleus; Cell Transformation, Neoplastic; DNA-Binding Proteins; Dose-Response Relationship, Drug; Erythrocytes; Erythroid Precursor Cells; Erythroid-Specific DNA-Binding Factors; Erythropoiesis; GATA1 Transcription Factor; Gene Expression Regulation, Leukemic; Hemoglobins; Humans; K562 Cells; Leukemia; Microscopy, Confocal; Phosphoric Monoester Hydrolases; Phosphorylation; Transcription Factors

In myeloid leukemia, immature leukemic cells are able to egress into peripheral blood to infiltrate extra-medullary organs. We therefore analyzed the migrating and invasive potential of human HL-60 and NB4 cell lines, representative of acute myelogenous leukemia, their ability to express matrix metalloproteases (MMPs), tissue inhibitors of metalloproteases (TIMPs) and urokinase plasminogen activator (uPA) in response to differentiating agents. Granulocytic differentiation by all-trans-retinoic acid (ATRA) and aclacinomycin (ACLA) strongly increased HL-60 and NB4 cell migration and invasion. At mRNA and protein levels, these cell lines produced significant amounts of MMP-9 (HL-60

Topics: Aclarubicin; Antineoplastic Agents; Cell Differentiation; Cell Movement; HL-60 Cells; Humans; Leukemia; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Phenylalanine; Serine Endopeptidases; Thiophenes; Tissue Inhibitor of Metalloproteinases; Tretinoin; Tumor Cells, Cultured

To investigate the feasibility and effectiveness of low density lipoprotein (LDL) particles as a carrier of a lipophilic anthracycline drug aclarubicin (ACR) for targeting delivery to an acute monocytic leukemia cell line THP-1.. LDL-ACR complex was prepared by incubating LDL with ACR. The intracellular ACR content was assayed fluorometrically. Cytotoxicity was studied by cell protein measurement and 3H-TdR incorporation test.. Intracellular accumulation of LDL-ACR was reduced when THP-1 cells were incubated in the presence of native LDL, but methylated LDL had no effect on the cellular LDL-ACR accumulation. The LDL-ACR complex caused a greater inhibition of the growth of THP-1 cells than that of normal bone marrow nucleated cells. The cellular accumulation of LDL-ACR complex was much more than that of free ACR. The 3H-TdR incorporation test showed that the complex was more effective in the inhibition of DNA synthesis than that of the free drug.. The potency of ACR to tumor cells increased and its toxicity to normal cells decreased when LDL was used as a carrier.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Cell Line, Tumor; Cell Proliferation; DNA; Humans; Leukemia; Lipoproteins, LDL

Topics: Aclarubicin; Acute Disease; Adult; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cohort Studies; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Finland; Humans; Immunocompromised Host; Incidence; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Pneumonia, Pneumocystis; Prednisone; Premedication; Retrospective Studies; Thioguanine; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

A new anthracycline antibiotic, designated as aclacinomycin X, was isolated from the culture broth of Streptomyces galilaeus ATCC 31133, and was identified as 7-(O-rhodosaminyl-deoxyfucosyl-rednosyl)- aklavinone. Its in vitro cytotoxicity was tested against several human tumor cell lines.

Topics: Aclarubicin; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Cell Division; Culture Media; Humans; Leukemia; Magnetic Resonance Spectroscopy; Melanoma; Streptomyces; Tumor Cells, Cultured

The induction of differentiation is at present one of the most promising pathway used in the field of cancer chemotherapy. As part of this research, the study of the human K562 erythroleukemic cells differentiation has shown that these cells are potent to synthesize hemoglobin when treated by 40 nmoles/l of adriamycin, 30 nmoles/l of aclacinomycin or 3.10(4) nmoles/l of hemin. This functional differentiation is accompanied by some changes in three membrane antigens expression: GPA, CD15 antigen and TfR. To complete these result, we have studied the differentiation of resistant K562 cells to adriamycin by these three inducers. Our results suggest that this cell population is able to synthesize hemoglobin after its exposition to 2.10(3) nmoles/l of adriamycin, 100 nmoles/l of aclacinomycin or 7, 5.10(4) nmoles/l of hemin. In contrary to aclacinomycin and adriamycin, hemin did not affect the three markers expression. On the other hand, only the induction by adriamycin causes membrane phenotypical changes which are erythroid differentiation specific.

Topics: Aclarubicin; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Differentiation; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Microbial; Erythrocytes; Glycophorins; Hemin; Hemoglobins; Humans; In Vitro Techniques; Leukemia; Lewis X Antigen; Receptors, Transferrin

K562 human leukemia cell line undergoes in vitro terminal differentiation towards the erythroid pathway following treatments with appropriate chemical agents including aclacinomycin, fagaronine and hemin. These three drugs induced a different expression of phenotypic and functional characters associated with differentiation. The morphological characteristics of the differentiation sequences elicited by these agents were evaluated by image analysis using a SAMBA 200 cell image processor. Multivariate statistical analyses of morphological data revealed that only aclacinomycin was able to induce significant modifications of the morphological parameters similar to those observed during the maturation of normal bone-marrow erythroblastic cells. These data correlate with the higher inductive potency of aclacinomycin as compared to hemin or fagaronine and suggest that quantitative cytology may be a useful adjunct to conventional tests for the selection of new drugs with differentiating potential.

Topics: Aclarubicin; Alkaloids; Benzophenanthridines; Cell Differentiation; Erythroblasts; Hemin; Hemoglobins; Humans; Leukemia; Phenanthridines; Tumor Cells, Cultured

We developed an effective method for harvesting large numbers of peripheral blood stem cells (PBSC) for use in autotransplantation. Twenty patients with hematological malignancies were treated with high doses of Ara-C (12 g/m2) and VP-16/aclarubicin followed by administration of rhG-CSF (50 micrograms/m2). The optimal time for starting PBSC collection was determined by monitoring the CD34-positive stem cells in blood using immunomagnetic beads. PBSC were collected with a CS-3000 blood cell separator. A total blood volume between 7000 and 9000 ml was processed in each apheresis. Under these conditions, a total of 64 apheresis procedures was performed in the 20 patients. The mean numbers of mononuclear cells and of CFU-GM harvested per apheresis were 4.1 x 10(8)/kg and 110 x 10(4)/kg, respectively. A number of CFU-GM sufficient for engraftment (> 30 x 10(4)/kg) could be harvested by a single apheresis in 15 of the 20 patients. So far, 11 patients have been transplanted with PBSC and obtained rapid hematopoietic recovery. The median time to recover neutrophils more than 0.5 x 10(9)/l was 10 days, and that for platelets 50 x 10(9)/l was 11 days. This method for harvesting large numbers of PBSC allows safer autotransplantation in patients with chemoradiosensitive tumors, and is applicable to older patients.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Cells; Blood Component Removal; Blood Transfusion, Autologous; Cytarabine; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Leukemia; Lymphoma; Male; Middle Aged; Recombinant Proteins

The growth fraction, estimated by the monoclonal antibody Ki-67 labeling, and DNA content, assessed by ethidium bromide staining, were determined simultaneously in K562 leukemic cells by flow cytometry. A multiparametric analysis enabled the fraction of the cell population with G1, S, and G2 + M contents in Ki-67-positive and Ki-67-negative cells to be evaluated. Butyric acid (BUT) was used as positive control. The fraction of Ki-positive cells decreased with the BUT concentration, while the proportion of cells with G1 DNA content increased only in the Ki-negative cells. Adriamycin, aclacinomycin A, and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreased the fraction of Ki-positive cells by more than 50% for both anthracyclines and by 25% for fagaronine. Following treatment, Ki-negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Topics: Aclarubicin; Alkaloids; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Antineoplastic Agents; Benzophenanthridines; Butyrates; Butyric Acid; Cell Differentiation; Cell Division; DNA, Neoplasm; Doxorubicin; Humans; Ki-67 Antigen; Leukemia; Nuclear Proteins; Phenanthridines; Proliferating Cell Nuclear Antigen; Tumor Cells, Cultured

The growth fraction of cancer cells, estimated by the monoclonal antibody Ki-67 labelling, and DNA content were determined simultaneously en K562 human leukemic cells by flow cytometry. Adriamycin, aclacinomycin A and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreases the fraction of Ki-67 positive cells, Ki-67 negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Topics: Aclarubicin; Alkaloids; Antibodies, Monoclonal; Antineoplastic Agents; Benzophenanthridines; Cell Transformation, Neoplastic; DNA; Doxorubicin; Flow Cytometry; Humans; Leukemia; Phenanthridines

Topics: Aclarubicin; Acute Disease; Aged; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 8; Cytarabine; Female; Humans; Leukemia; Phenotype; Translocation, Genetic

Topics: Aclarubicin; Antineoplastic Agents; Cytarabine; Dose-Response Relationship, Drug; Humans; Leukemia; Naphthacenes; Neutrophils; Superoxides

Topics: Aclarubicin; Acute Disease; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia; Male; Middle Aged; Naphthacenes; Thioguanine

A 12-year-old girl with acute non-lymphocytic leukemia was treated with a protocol involving high-dose cytosine arabinoside (Ara-C) for intensification of early therapy. The patient, who had been revealed to have CNS infiltration on admission, achieved complete remission after receiving ACMA/BHAC combination and intrathecal MTX. As an early intensification treatment, ID/HD Ara-C was safely and effectively administered; this consisted of ADR (45 mg/m2 iv) Day 1, intermediate-dose Ara-C (0.5 g/m2, 1-h drip, q. 12 h) Days 2-4, and high-dose Ara-C (3 g/m2, 3-h drip, q. 12 h) Days 10-11, followed by L-asp (6,000 U/m2, im) on Day 12. Ten months later, the patient has been in continuous complete remission. High-dose Ara-C should be included with caution as an early intensification of treatment to improve the therapeutic results of childhood ANLL.

Topics: Aclarubicin; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Female; Humans; Leukemia; Methotrexate; Naphthacenes; Vincristine

Topics: Aclarubicin; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Humans; Leukemia; Naphthacenes; Thioguanine

Twenty-one patients with previously untreated acute leukemia were treated with a combination chemotherapy of 120-200 mg/m2 of aclacinomycin A (ACM-A) in five divided daily doses and behenoyl-arabinofuranosylcytosine (BH-AC) 200-250 mg/m2 for 7 days at Saitama Cancer Center between April 1980 and July 1983. Complete remission was obtained in 12 of 21 patients (57.1%; M1 0/1, M2 10/10, M3 0/2, M4 1/3, leukemic transformation from sideroblastic anemia 0/1, refractory anemia with excess of blasts in transformation 1/2, chronic myelomonocytic leukemia 0/1). Seven of 9 patients who failed to have complete remission were crossed over to a combination chemotherapy of daunorubicin (DNR) plus BH-AC or cytosine arabinoside (ara-C), or single DNR for patients with M3, yielding complete remission in 5 patients. Seven patients received a total cumulative dose of more than 600 mg/m2 of ACM-A. The maximum dose given was 2,000 mg/m2. No congestive heart failure has yet been experienced. The median survival time was 12 months. These results have demonstrated that a combination of ACM-A and BH-AC shows almost equivalent activity with that of a standard induction therapy consisting of DNR plus ara-C. In addition, it was suggested that ACM-A plus BH-AC could be incorporated into reinforcement therapy because of supposedly less cardiac toxicity.

Topics: Aclarubicin; Actuarial Analysis; Acute Disease; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Child, Preschool; Cytarabine; Humans; Leukemia; Middle Aged; Naphthacenes

The pharmacokinetics of aclarubicin, a new anthracycline antibiotic, was studied in five patients with acute leukemia or in L1210 cell suspension. Aclarubicin disappeared very rapidly from plasma and whole blood after administration at a dose of 20 mg per patient by iv bolus injection. The concentration of active metabolite M1, on the other hand, increased for up to 2 or 4 hrs after administration and exceeded that of aclarubicin, and then remained at much higher concentrations than aclarubicin for up to 24 hrs after administration. In addition, the levels of aclarubicin and its metabolites in whole blood were much higher than the corresponding plasma levels in four of the patients. The drug concentrations in blood cells of 11 patients determined 4 hrs after administration showed a significant positive correlation with leukocyte counts. Moreover, the concentration of aclarubicin and its metabolites was found to be much higher in the leukocyte fraction than in the erythrocyte fraction in vivo and in vitro. These findings indicate that aclarubicin and its metabolites in blood cells were mainly accumulated in leukocytes. In the study of intracellular drug distribution in L1210 cells, the largest amount of aclarubicin was incorporated into the nuclear fraction. This suggests a close relationship between the pronounced drug accumulation in leukocytes and the high affinity of aclarubicin for DNA.

Topics: Aclarubicin; Acute Disease; Adult; Aged; Animals; Antibiotics, Antineoplastic; Blood Cells; Cell Fractionation; Cell Line; Cell Nucleus; Chromatography, High Pressure Liquid; Erythrocytes; Humans; Kinetics; Leukemia; Leukemia L1210; Leukocytes; Naphthacenes; Radioimmunoassay

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Hemorrhage; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Mucous Membrane; Naphthacenes; Prednisolone; Urinary Bladder Diseases

Mitoxantrone, a new anthracenedione, was administered to thirty-nine patients with relapsed and refractory acute leukemia and to 12 patients with blastic crisis of chronic myelogenous leukemia between August 1981 and September 1984. Eleven patients were not evaluable and 40 were analysed. There were 24 males and 16 females with a median age of 37 yrs (range 6-73 yrs). Three of these were less than 15 yrs and 7 more than 60 yrs. The initial dose employed was 1.9 mg/m2/day X 5. Although eventually a starting dose of 12.3 mg/m2/day X 5 was used, about one half of cases were given more than 5 mg/m2/day X 5 by i.v. bolus. Among 25 patients with acute non-lymphocytic leukemia, there were 4 complete and 6 partial remissions. Among 7 patients with acute lymphocytic leukemia there was one complete remission and one partial remission. All patients except one who attained remissions had received prior anthracyclines. One of 8 patients with blastic crisis of chronic myelogenous leukemia had a partial remission. The durations of complete remission were 1, 1, 5+, 13+ and 17 weeks, respectively. Side-effects showed expected bone marrow depression. Mucositis occurred in ten patients. Gastrointestinal symptoms were noted in approximately 50%, but were mostly mild. Mild alopecia occurred occasionally. The trials were too short to allow evaluation of possible cardiac toxicity. These data indicate that mitoxantrone is non-toxic but hematological and a promising single drug for use in treating relapsed and refractory acute leukemia and suggest that further study would be worthwhile in order to identify its role in the first-line therapy of acute leukemia.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Blast Crisis; Child; Daunorubicin; Drug Evaluation; Drug Resistance; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Middle Aged; Mitoxantrone; Naphthacenes

Topics: Aclarubicin; Acute Disease; Adult; Antineoplastic Agents; Cytarabine; Doxorubicin; Drug Evaluation; Humans; Interferon Type I; Leukemia; Naphthacenes

A phase II study of mitoxantrone (Novantrone; dihydroxyanthracenedione) was conducted in 35 patients (22 male: 13 female) with acute leukemia. There were 35 evaluable cases with a mean age of 34 (range 8-61). Twenty-eight patients had acute non-lymphocytic leukemia (ANLL) and seven had acute lymphocytic leukemia (ALL). Mitoxantrone was administered intravenously 2-4 mg/m2 daily for five days and after the nadir a further 2-3 doses were added if necessary. All previously treated cases (22 patients) had been treated with anthracyclines; 13 had no previous treatment. Out of the 13 untreated cases there were six complete remissions (CRs) (46.2%) and five partial remissions (PRs) (38.5%), while out of 22 pretreated cases, four CRs (18.2%) and five PRs (22.7%) were obtained. In seven of the untreated cases the decrease of leukemic cells and neutrophil leukocytes were analysed. Mitoxantrone showed a longer duration of decrease and higher log decrease of leukemic cells in the bone marrow than daunorubicin or cytosine arabinoside. Seventy-three percent of patients showed gastrointestinal disturbances such as nausea or loss of appetite. In 38.1% SGPT elevation and in 8.8% abnormal ECG findings were observed. All side-effects were mild and reversible. From this data mitoxantrone seems a very promising agent in the treatment of acute leukemia and a phase III study is now being carried out.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Alanine Transaminase; Anthraquinones; Antineoplastic Agents; Child; Daunorubicin; Doxorubicin; Drug Evaluation; Drug Resistance; Electrocardiography; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukocyte Count; Male; Middle Aged; Mitoxantrone; Naphthacenes

Topics: Aclarubicin; Acute Disease; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Digestive System; Female; Gastrointestinal Diseases; Humans; Leukemia; Male; Mercaptopurine; Naphthacenes; Prednisolone

Recently marked progress in many fields around the treatment of acute leukemia has resulted a marked improvement in the therapeutic results. Establishment of fundamental principles of therapy, i.e., understanding of remission induction, consolidation and maintenance has supported a systemic analysis of treatment. New antileukemia drugs such as Aclacinomycin, THP-adriamycin, Epirubicin, Mitoxantrone, Vindesine, Etoposide, PL-AC together with the immunotherapeutic agent i.e., Bestatin, kurestin and Nocardia-CWS were studied and found to show their merits in the treatment. Monitoring the patients by 5000 leukocyte differential or the development of new antibiotics or improvement of laminar air flow rooms etc, has supported the antileukemic therapy. Bone marrow transplantation, allogeneic, syngeneic or autologous, has shown a very rapid progress and is proved to be a reliable treatment with very high rate of complete cure.

Topics: Aclarubicin; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Doxorubicin; Humans; Leukemia; Naphthacenes; Vincristine; Vindesine

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Naphthacenes; Pancreatitis; Prednisolone

The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-MLs) to doxorubicin (DOX), aclacinomycin (ACL), and 4'-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-MLs. CFU-MLs from untreated patients were sensitive to the three tested anthracyclines (in 60% to 69% of the patients). Conversely, CFU-MLs from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71% and 75% of the patients, respectively) but resistant to DOX. Six of ten patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-MLs in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-MLs which were sensitive in vitro to DOX. Nine of ten patients who responded to ACL as well as one of three resistant patients had CFU-MLs sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in five of seven patients with CFU-MLs sensitive to this drug. The results indicate that myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-MLs to compounds with established antileukemic activity (ie, DOX, ACL). However, the discrepancy between in vitro and in vivo sensitivity to THP-DOX underlines the importance of knowledge of drug pharmacokinetics and the difficulty of using the CFU-ML test for screening new drugs.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Dose-Response Relationship, Drug; Doxorubicin; Humans; In Vitro Techniques; Leukemia; Naphthacenes; Neoplastic Stem Cells; Stem Cells; Tumor Stem Cell Assay

Aclarubicin (ACR) was administered in a prospective cooperative phase II trial to 44 patients with possibly refractory acute nonlymphocytic leukemia who were previously treated with daunorubicin and cytarabine. Induction treatment consisted of 80 mg/m2 of ACR iv daily for 3 days, followed by 80 mg/m2 iv daily for 2 days in patients not obtaining a complete remission (CR) after 2-4 weeks. CR was observed in eight patients (18%) and partial remission was observed in six (14%). On monthly maintenance chemotherapy with ACR and cytarabine, the duration of CRs varied between 10 and 58 weeks. Achievement of remission was not related to age, presence or absence of Auer bodies, cytogenetic characteristics, or previous response to daunorubicin and cytarabine. Side effects were nausea and vomiting observed in 86% and diarrhea in 34% of the patients, whereas mucositis and alopecia were uncommon. Disturbances of cardiac function arousing suspicion of acute ACR toxicity were observed in seven patients. No case of chronic cardiotoxicity was observed, despite the fact that 20 patients received ACR doses greater than 400 mg/m2, with seven of the 20 having had a previous daunorubicin dose greater than 400 mg/m2. As CR was obtained in four of 14 patients with primary therapy-resistant leukemia and in two of 16 patients with relapse and no response to re-treatment with daunorubicin and cytarabine, ACR does not seem to show clinical cross-resistance to daunorubicin. Evaluation of ACR in first-line chemotherapy of acute nonlymphocytic leukemia appears justified.

Topics: Aclarubicin; Acute Disease; Adult; Aged; Antibiotics, Antineoplastic; Cytarabine; Daunorubicin; Drug Evaluation; Heart; Humans; Leukemia; Leukopenia; Middle Aged; Naphthacenes; Prospective Studies; Thrombocytopenia

Topics: Aclarubicin; Acute Disease; Animals; Antibiotics, Antineoplastic; Cricetinae; Drug Evaluation; Humans; Leukemia; Naphthacenes; Neoplasms

We analysed the effects of three different regimens for first induction therapy with 50 cases of acute nonlymphocytic leukemia in adults and reported the results of combination therapy including aclacinomycin for reinduction therapy. Results obtained were as follows: The regimens of DCMP 2 step and Cc, P were superior to DCMP in remission rate (78%, 78% and 41%), median duration of CR (8.3 months, 5.0 months and 3.5 months) and survival time (6.5 months, 11.5 months and 2 months). Cc, P regimens obtained favorable CR rate in elderly patients over 50 years of age. (Cc, P: 100%, others: 40-50%) No significant difference in survival time was observed in patients who attained CR by three different regimens. In patients treated with combination therapy including aclacinomycin, the CR rate was 89% in the 9 previously treated patients (5 relapse cases and 4 refractory leukemias): All of these patients had previously been treated with DCMP 2 step or BHAC-DMP. Daunomycin (D), Cytosine Arabinoside (C), 6-Mercaptopurine (M) and Prednisolone (P) (DCMP), DCMP 2 step and Cyclocytidine (Cc) P.

Topics: Aclarubicin; Acute Disease; Adult; Age Factors; Ancitabine; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models. A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response. All suffered from recurrent and advanced tumors. Pretreatment consisted of at least four different chemotherapeutic agents (range: 4-9). Lung cancer patients (3/9) were irradiated to the mediastinum. Eighteen patients were pretreated with doxo- or daunomycin. The dose for solid tumors was 2-3 mg/kg given on 3 consecutive days every 3 weeks. Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used. Marked reductions of leukocyte counts were achieved in leukemia patients. The overall response rate was about 15% in solid tumors, but major objective responses (CR + PR) have not been observed. Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced. Cumulative cardiotoxicity was not evaluated in this trial. Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Leukemia; Leukopenia; Lung Neoplasms; Male; Middle Aged; Naphthacenes; Nausea; Thrombocytopenia

Twenty-two patients with adult acute non-lymphocytic leukemia treated with intensive combination chemotherapy between November 1975 and April 1982 were retrospectively analyzed to see if we could find useful clinical parameters which could predict those patients who, after failing their initial treatment cycle, would respond to subsequent cycles of the same regimen. Three groups of patients were identified. Eight patients achieved complete remission with one cycle of chemotherapy; seven patients achieved complete remission with a second cycle of the same regimen and seven patients did not respond. Marrow studies performed approximately 3 weeks following the first cycle of therapy were analyzed. Patients who subsequently responded to the regimen differed from non-responders in the residual blasts percentage in the marrow obtained 20-24 days after the initiation of the first cycle. Patients who responded to a second cycle had 11-36% blasts (mean 24%), while non-responders had 35-96% blasts (mean 66%) (p less than 0.01). No patients with more than 40% blasts in their bone marrow achieved complete remission. We concluded that patients with more than 40% blasts in their bone marrow 20-24 days after the initiation of the first cycle of the chemotherapy regimens used should receive an alternate regimen for a second cycle of induction therapy.

Topics: Aclarubicin; Adult; Antineoplastic Agents; Bone Marrow Examination; Daunorubicin; Drug Resistance; Drug Therapy, Combination; Humans; Leukemia; Naphthacenes; Retrospective Studies

Sixteen patients with previously untreated acute nonlymphocytic leukemia were treated with a combination of aclacinomycin A (ACM-A) and behenoyl ara-C (BH-AC) at Saitama Cancer Center between April 1980 and February 1983. The complete remission was obtained in 10 of 16 patients (62.5%) (M1, 0/1 M2, 8/8, M3, 0/2, M4, 2/5). A combination of daunorubicin (DNR) and cytosine arabinoside (ARA-C) was crossed over to 5 patients who failed to respond to primary treatment of a combined ACM-A and BH-AC. All of these attained the complete remission. The cumulative dose of over 600 mg/m2 of ACM-A has been given to 7 patients as maintenance treatment. The maximum cumulative dose was 2000 mg/m2. The median survival time for all patients was 12 months, and the median survival with complete remission has not been reached; however, it is estimated to be greater than 24 months. ACM-A seemed to induce long-term maintenance when it was used as maintenance treatment. The results have demonstrated that a combination of ACM-A and BH-AC shows equivalent activity with that of a combined DNR and ARA-C in terms of remission induction and remission maintenance.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Female; Humans; Leukemia; Male; Middle Aged; Naphthacenes

Aclacinomycine-A (ACM), a new anthracycline derivative, was administered intravenously to 50 patients in doses of 10-30 mg/m2/day for periods of 6 to 30 days. Among the 45 patients who could be assessed, 17 were suffering from acute myeloid leukaemia, 19 from acute lymphoid leukaemia and 9 from non-hodgkin lymphoma. The results confirmed those first published by the authors in 1978 and led them to propose new measures aimed at reducing the toxicity of ACM. Depending on the dosage, complete or partial (more than 50%) remissions were obtained in patients with acute myeloid leukaemia. In the 19 patients with acute lymphoid leukaemia, complete remission was observed in 2 and partial remission in 2. Among the 9 patients with non-hodgkin lymphoma, there was 3 complete and 1 partial remissions. ACM did not produce alopecia and, as predicted by the authors' experimental study on hamsters, did not have major cardiac toxicity. The gastrointestinal toxicity, which had forced a reduction of the total dose in the first trial, proved moderate, even with normal dosage.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Antibiotics, Antineoplastic; Child; Child, Preschool; Drug Evaluation; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Naphthacenes

Aclacinomycin A (ACM) is a new anthracycline antibiotic that produces substantially less cardiotoxicity in animals than does doxorubicin. To define the effective dose for the treatment of patients with leukemia, we treated 43 patients with acute nonlymphoblastic leukemia (ANLL) or acute lymphoblastic leukemia (ALL) using ACM administered at three dose levels. All patients had previously received extensive treatment with other chemotherapy; their median cumulative dose of prior anthracycline was 340 mg/m2. An ACM dose of 100 mg/m2/day given for 2 days (total dose, 200 mg/m2) failed to produce significant bone marrow hypocellularity or remission in two patients. Total ACM doses of 300--360 mg/m2 (100 or 120 mg/m2/day x 3 days) produced marrow hypoplasia in 16 to 23 evaluable patients with ANLL. Overall, four of 32 patients with ANLL who received 300--360 mg/m2 of ACM achieved complete remission for duration of 1, 5+, 6 and 15+ months. Two of nine patients with ALL achieved partial remission. Toxic effects of this therapy included severe leukopenia and thrombocytopenia, nausea, mucositis, and diarrhea. ECG abnormalities were noted in 43% of patients who were carefully monitored; however, only one patient developed a significant decrease in left ventricular ejection fraction as measured by radionuclide cardiography. ACM produced only minimal alopecia and did not cause tissue necrosis following inadvertent subcutaneous infiltration. We conclude that 300--360 mg/m2 of ACM is an effective dose for the treatment of patients with ANLL and that further evaluation of this compound is indicated in patients who have received minimal prior therapy.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Heart Diseases; Humans; Leukemia; Leukemia, Lymphoid; Middle Aged; Naphthacenes; Neutropenia; Thrombocytopenia

Anthracycline antibiotics are principal agents in the treatment of acute non-lymphocytic leukemia, although the usefulness are limited by their adverse side effects, especially by the cardiotoxicity. Aclacinomycin A (ACM) is known to be a new anthracycline antibiotic which has been isolated from Streptomyces galilaeus, and its cardiotoxicity on the experimental animal systems was reported to be more than 10 times lower than that of adriamycin. We investigated the cardiotoxicity of ACM on 29 patients with acute leukemia and compared it with daunorubicin (DNR). The measurement of STI (PEP:LVET) has been recommended to be convenient method of assessing the anthracycline cardiotoxicity, but through out analytical study, QTC measurement was proved to be more valuable for the simple and rapid detection of the cardiotoxicity induced by the agents. In comparison with the QTCs in DNR and ACM, the cardiotoxicity of ACM was much lower than that of DNR, and the reversibility of ACM induced cardiotoxicity was much more rapid. Moreover, these effects were observed even in the patients treated with the maximum dose of DNR. Therefore, ACM was expected to be one of the agents of the first choice for the relapsed cases of acute leukemia, especially APL.

Topics: Aclarubicin; Acute Disease; Adult; Antibiotics, Antineoplastic; Daunorubicin; Electrocardiography; Female; Heart; Humans; Leukemia; Male; Naphthacenes; Systole

A comparative trial of a combination of daunorubicin and cytosine arabinoside (Regimen A) and a combination of aclarubicin and cytosine arabinoside (Regimen B) was performed. Sixteen patients with acute non-lymphocytic leukemia, previously untreated, were entered into this study. Five of 8 patients (62.5%) obtained a complete remission (CR) in Regimen A and B, respectively. The days required for achieving a CR varied from 37 to 46 days in Regimen A and from 22 to 56 days in Regimen B. The total doses of daunorubicin and cytosine arabinoside were from 100 to 240 mg and from 640 to 1,120 mg in Regimen A, respectively. Those of aclarubicin were from 180 to 300 mg and from 660 to 1,000 mg in cytosine arabinoside in Regimen B. In a comparative study on hematological changes, toxic effects on peripheral white blood cell, platelet and nucleated cell counts in bone marrow tended to appear later in Regimen B compared to those in Regimen A. Side effects on digestive system such as nausea and vomiting and vascular pain were more frequently recognized in patients treated with Regimen B, although they were managed by symptomatic treatment. The results indicated the usefullness of aclarubicin in combination chemotherapy for the treatment of acute non-lymphocytic leukemia.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Naphthacenes; Random Allocation

Topics: Aclarubicin; Adult; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

Future studies with daunorubicin involve mainly comparative evaluations with other anthracycline antibiotics and related compounds. Efforts are ongoing to improve the therapeutic index of these drugs. This includes not only laboratory development but also clinical evaluation of analogs, manipulations in dose schedules, and the use of protectors of toxic manifestations, primarily of cardiomyopathy. Technological advances in the clinical area permit, for example, the exploration of daunorubicin and related compounds by continuous infusion under more precise pharmacologic and cardiologic monitoring than was possible when they were initially introduced.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carubicin; Child; Daunorubicin; Doxorubicin; Drug Evaluation; Humans; Leukemia; Naphthacenes; Structure-Activity Relationship

Topics: Aclarubicin; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Child; Drug Evaluation; Female; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Middle Aged; Naphthacenes

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Leukemia; Male; Middle Aged; Naphthacenes