pirarubicin and Acute-Disease

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

Various methods of intensive chemotherapy have contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long-term results of the two consecutive trials of Tokyo Children's Cancer Study Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C) based combination chemotherapy in post-remission phase.. A total of 216 eligible children with newly diagnosed AML were treated in the two consecutive multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September 1998. In M91-13 trial, patients received eight courses of intensive post-remission chemotherapy, including six HD-Ara-C containing courses, after remission-induction therapy. Autologous hematopoietic stem cell transplantation (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated if donor was available. In M96-14 trial, the last two HD-Ara-C courses were omitted from the chemotherapy arm.. The remission-induction rate was 88.8% and probability of 5-year Overall survival (OS) and event-free survival (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%), respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21) or inv(16) was a significant good prognostic factor both in the univariate and multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a good survival exceeding 70% in 5 years.. These results suggest that repetitive use of HD-Ara-C was effective and safe for childhood AML. However, further optimization of AML therapy is required.

Topics: Acute Disease; Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Hydrocortisone; Infant; Infections; Japan; Kaplan-Meier Estimate; Leukemia, Myeloid; Male; Methotrexate; Mitoxantrone; Remission Induction; Survival Analysis; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Tretinoin; Vincristine

(2'' R)-4'-O-Tetrahydropyranyl Adriamycin (THP) is a new antitumor agent discovered among series of similar anthracycline compound synthesized by Umezawa et al. Phase I study revealed dose limiting factor of leukopenia with upper GI toxicity. Alopecia, cardiac failure and transient hepatic failure were extremely mild. Definite responses were demonstrated in acute leukemia, lymphoma, ovarian carcinoma, head and neck carcinoma, breast carcinoma and GU carcinoma. Pharmacokinetic studies revealed rapid cell uptake and outputs in bile (20%) and urine (8%) in 24 hours. Transfer to third spaces were poor but definite. In vivo a part of THP was converted to ADM in the liver, but not in other tissues including tumors. THP would be an extremely interesting compound, because of comparable spectrum of responses to various tumors with extremely low toxicity compared with other anthracycline compounds.

Topics: Acute Disease; Clinical Trials as Topic; Doxorubicin; Gastrointestinal Diseases; Humans; Leukemia; Lymphoma; Neoplasms

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

An 82-year-old man was admitted to our hospital in September 1996 due to dysphagia and cardiomegaly. Physical examination detected the fourth heart sound and a Levine III/VI systolic murmur in the cardiac apex. Surface lymph nodes were not palpable. LDH 662 IU/I was detected by laboratory examinations, and ultrasound cardiography showed grade 3 mitral regurgitation. Computed tomography revealed a huge mass in the posterior mediastinum, pressing the heart from the posterior direction. Thereafter, a left pleural effusion developed and aspiration was performed. Cytological examination of the fluid showed clusters of lymphoid cells with a positive immunophenotype for CD10, CD19 and HLA-DR. Chromosome analysis revealed complex abnormal karyotypes including t(8;14) (q24;32). A diagnosis of B cell lymphoma was made, and combination chemotherapy consisting of cyclophosphamide, THP-adriamycin, vincristine, and prednisolone was initiated. The patient's mass disappeared promptly, and his mitral reguration subsided. We reported this case because malignant lymphoma of the posterior mediastinum is rare, and because we are unaware of any previous reports of malignant lymphoma causing acute mitral regurgitation.

Topics: Acute Disease; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Humans; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Mitral Valve Insufficiency; Prednisolone; Vincristine

Confocal microspectrofluorometry allows the analysis of fluorescent molecules such as anthracylines in isolated living cells. An optical microscope fitted with a phase-contrast 100 X water-immersion objective enables simultaneous observation of the sample, focusing of the laser beam on the selected cell fraction (nucleus) and collection of the fluorescence emitted from the sample. The resulting intranuclear spectra are interpreted according to a quantitative model of the fluorescence spectra of both free and DNA-bound anthracycline. The intranuclear drug concentration can thus be determined. This technique has been applied to blast cells collected in patients with acute leukemia. Leukemic cells are aspirated from bone marrow, separated by Ficoll sedimentation and resuspended in RPMI-1640 containing 10% fetal calf serum and 200 nM tetrahydropyranyl-doxorubicin (THP-DOX). After one hour, 20 cells are analyzed and the mean nuclear drug content is determined (C1). Cells are then resuspended in the same medium but without anthracycline for 3 hours and the mean intranuclear drug concentration is then also determined (C3). From C1 and C3 the retention rate (RR) is calculated. Firstly, the accuracy of the method was checked. In 4 AML patients, two different samples aspirated on the same day were divided into two portions. Thus, two measurements were made on each one (4 values per patient). Coefficients of variation were satisfactory (4, 6, 12, and 12%). Secondly, blast cells collected in patients with AML and ALL at diagnosis or in relapse were studied. P-glycoprotein (P-gp) and CD34 expression was also studied using respectively immunohistochemistry land flow cytometry. Results obtained from the first 21 patients showed that there was no correlation between RR and either P-gp or CD34 expression. This could result from the efflux of THP-DOX by other mechanisms and/or low sensitivity of the staining technique.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antigens, CD34; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Bone Marrow; Cell Nucleus; Child; Doxorubicin; Drug Resistance, Multiple; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid; Microscopy, Confocal; Microspectrophotometry; Middle Aged; Phenotype; Precursor Cell Lymphoblastic Leukemia-Lymphoma

For the purpose of establishing a method for reasonable clinical use of anthracyclines in leukemia chemotherapy, we examined the pharmacokinetics and the mode of action with five anthracyclines such as daunorubicin (DNR), doxorubicin (DOX), aclarubicin (ACR), THP adriamycin (THP), idarubicin (IDA). In the patients with AML, blood ACR or IDA level increased and then disappeared very rapidly after iv bolus injection. In contrast, their metabolites (M1 or IDAol) increased for up to 2 or 4 hrs and remained much longer than ACR or IDA. The concentration of ACR, IDA or their metabolites were found to be much higher in the leukocyte fraction than in erythrocyte fraction or plasma. In HL60 cell suspension, anthracyclines were rapidly accumulated into the cells, and the uptake of IDA or THP were higher than the other agents. In HL60 cells, anthracyclines accumulated in the nuclear fraction but ACR was accumulated markedly in the cytosol fraction. From the result of DNA binding assay, binding at excess to calf thymus DNA of ACR was suggested to be approximately 2 times higher than that of other agents. DNA strand brakes in HL60 cells treated with anthracyclines were shown by pulse field gel electrophoresis, and IDA was found to have stronger activity to cause the DNA strand breaks. In conclusion, it seemed that anthracyclines showed similar action mechanisms, but in some respects quantitative differences were existed among them. Anthracyclines should be given to patients based on their pharmacological characteristics to obtain higher remission rate and suppress resistant cells.

Topics: Aclarubicin; Acute Disease; Antibiotics, Antineoplastic; Daunorubicin; DNA; DNA Damage; DNA Replication; Doxorubicin; Humans; Leukemia, Myeloid

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13-34 mg/m2 for 3-5 consecutive days or 35-50 mg/m2 at 3-4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Doxorubicin; Drug Evaluation; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged

A Phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was conducted in 162 patients with various hematological malignancies in a multi-institutional cooperative study. THP was given intravenously at a dose of either 10-30 mg/body for 3-5 consecutive days or 40-60 mg/body at 3-week intervals. Of 22 patients with AML, complete remission (CR) was observed in 2 patients and partial remission (PR) in 2. Of 18 patients with ALL, CR was observed in 5 and PR in 3. Of 68 patients with NHL, CR was observed in 11 and PR in 22. Of 8 patients with HD, CR was observed in 4 and PR in 2. One CML case showed CR and one ATL case showed PR. PR was noted in one of 2 patients with mycosis fungoides. Overall remission rate was 43.1% (CR 23 cases and PR 33 cases). The predominant toxicity was myelosuppression. Leukopenia (less than 4,000/mm3) was noted in 67 (77.6%) and thrombocytopenia (less than 10 X 10(4)/mm3) in 24 (27.0%). Nausea/vomiting and anorexia were common, and were observed in 61 (43.3%) and 65 (46.1%) cases, respectively. Hair loss and cardiotoxicity were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for various hematological malignancies including acute leukemia and malignant lymphoma.

Topics: Acute Disease; Adolescent; Adult; Aged; Anorexia; Antineoplastic Agents; Child; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukemia; Leukopenia; Lymphoma; Male; Middle Aged

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

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