carubicin and Leukemia--Myeloid--Acute

Idarubicin showed the superior activity against Acute Non-Lymphocytic Leukemia (ANLL) in the prospective randomized trials comparing to daunorubicin and it is judged that the analog will become the first choice in the treatment on ANLL. Anthracyclines including SM-5887, KRN-8602, ME-2303 under studies in Japan have shown comparable or superior antitumor activities and lower cardiac toxicities compared to doxorubicin in preclinical studies and therefore the results obtained in clinical trials are expected. Phase II trials of anthrapyrazoles which is an analog of mitoxantrone are in progress. Among three compounds entered it is of note that CI-941 has demonstrated an excellent activity against advanced breast cancer.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents; Brain Neoplasms; Carubicin; Doxorubicin; Humans; Idarubicin; Leukemia, Experimental; Leukemia, Myeloid, Acute; Menogaril; Stomach Neoplasms

In order to determine the clinically optimal dose of KRN8602, a new anthracycline derivative, in combination therapy for acute leukemia, we performed a pilot late phase II study in combination with cytarabine (Ara-C) for acute myelogenous leukemia (AML), and with vincristine (VCR) and prednisolone (PSL) for acute lymphocytic leukemia (ALL). KRN8602 was given at a dose of 12 or 15 mg/m2 for 5 consecutive days, Ara-C at a dose of 100 mg/m2 for 7 consecutive days, VCR 1.4 mg/m2 (max. 2.0 mg/body) weekly for 4 weeks, and PSL 40 mg/m2 for principally 28 consecutive days. Of 14 patients with relapsed or refractory leukemia entered in the study, thirteen patients were evaluable for safety and 12 were evaluable for response. In AML, there was 1 partial response (PR) in 4 patients at a dose of 12 mg/m2. Against 1 complete response (CR) and 3 PRs in 4 patients at a dose of 15 mg/m2. In ALL, there was 1 PR in 1 case at a dose of 12 mg/m2, and 1 CR and 2 PR in 3 at a dose of 15 mg/m2. Major toxicities were nausea/vomiting and anorexia, but incidences and grades of toxicities were not dose-dependent, and all toxicities were tolerable and manageable. From these results it is concluded that the optimal dose of KRN8602 is 15 mg/m2 for 5 consecutive days in combination with Ara-C for AML, and with VCR and PSL for ALL.

Topics: Adult; Aged; Anorexia; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carubicin; Cytarabine; Female; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Middle Aged; Nausea; Pilot Projects; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Remission Induction; Vincristine; Vomiting, Anticipatory

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

We performed an early phase II study of KRN8602, a new anthracycline derivative for refractory or relapsed acute leukemias. KRN8602 was given at a dose of 15 mg/m2 for 3 to 5 consecutive days, repeating every 3-4 weeks. Among 53 patients entered in the study, 51 were evaluable for safety, and 46 were evaluable for efficacy. The response rate at schedules of 3 and 4 consecutive days was 9.1% (1 PR/11), while that at a schedule of 5 consecutive days was 22.9% (3 CR + 5 PR/35). With the 5 consecutive day schedule, the response rates were 21.4% (1 CR + 2 PR/14) for acute myelogenous leukemia and 29.4% (2 CR + 3 PR/17) for acute lymphocytic leukemia, but no response was observed in 4 patients with blastic crisis of chronic myelogenous leukemia. Major toxicities were nausea/vomiting and anorexia, however, all these toxicities were clinically manageable. From these results it is concluded that KRN8602 is effective against acute leukemias, and the optimal dose is 15 mg/m2 for 5 consecutive days.

Topics: Adult; Aged; Anorexia; Antibiotics, Antineoplastic; Carubicin; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Nausea; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Vomiting

Idarubicin showed the superior activity against Acute Non-Lymphocytic Leukemia (ANLL) in the prospective randomized trials comparing to daunorubicin and it is judged that the analog will become the first choice in the treatment on ANLL. Anthracyclines including SM-5887, KRN-8602, ME-2303 under studies in Japan have shown comparable or superior antitumor activities and lower cardiac toxicities compared to doxorubicin in preclinical studies and therefore the results obtained in clinical trials are expected. Phase II trials of anthrapyrazoles which is an analog of mitoxantrone are in progress. Among three compounds entered it is of note that CI-941 has demonstrated an excellent activity against advanced breast cancer.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents; Brain Neoplasms; Carubicin; Doxorubicin; Humans; Idarubicin; Leukemia, Experimental; Leukemia, Myeloid, Acute; Menogaril; Stomach Neoplasms

Carminomycin is an original antitumor antibiotic from the anthracycline group isolated at the Institute of New Antibiotics (USSR) in 1973. Pharmacological investigation of carminomycin revealed its satisfactory absorption from the gastrointestinal tract which proved to be a distinguishing property of the antibiotic as compared to other anthracyclines such as adriamycin and rubomycin. The clinical trials of carminomycin showed that it was mainly active against soft tissue sarcoma and breast cancer, lymphosarcoma, neuroblastoma, Wilms' tumor and Ewing's sarcoma in children, as well as acute leukemia. Various regimens for the antibiotic administration were applied: short-term, single and long-term. Suppression of hemopoiesis was considered as a limiting toxic effect. By the data available carminomycin had lower cardiotoxicity as compared with rubomycin and adriamycin. Development of oral carminomycin is believed promising.

Topics: Adult; Breast Neoplasms; Carubicin; Child; Female; Humans; Kidney Neoplasms; Leukemia, Myeloid, Acute; Liver Neoplasms; Neoplasms; Sarcoma; Soft Tissue Neoplasms; Uterine Neoplasms; Wilms Tumor

The data on the clinical trials of karminomycin, a new antitumor antibiotic are presented. The drug was used in the treatment of 46 adult patients with leukemia. Karminomycin was used in primary inducing therapy and treatment of relapses. The results of the trials showed that karminomycin had a definite therapeutic activity in treatment of acute myeloblast leukemia at various stages of the process. A rapid effect of the antibiotic provided its use in emergency cases with rapidly progressing variants of the disease.

Topics: Adult; Antibiotics, Antineoplastic; Bone Marrow; Carubicin; Clinical Trials as Topic; Daunorubicin; Drug Evaluation; Drug Tolerance; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Time Factors

During the 1st stage of the clinical trials of karminomycin 92 patients with leukemia, solid tumors and lymphoma were treated with karminomycin. Two schemes for the antibiotic use were developed. The 1st scheme was a prolonged one with single doses of 10-15 mg (7.5 mg/m2) administered intravenously twice a week for 3 weeks, the course dose being 60-75 mg (34-45 mg/m2) with 4-week intervals between the courses. The course dose for the patients previously subjected to intensive chemotherapy did not exceed 50 mg (30 mg/m2). The 2nd scheme was a short one with single doses of 8-10 mg (5.5 mg/m2) administered intravenously every day for 5 days, the course dose being 40-50 mg (23-30 mg/m2) with 3-week intervals between the courses. Karminomycin induced in a number of patients a direct side effect, such as nausea, vomiting, asthenia, tachycardia, pain in the heart. In some patients leucopenia, thrombocitopenia, rare stomatitis, alopecia, lowered T peak in the chest curves of the cardiograms were observed after using the course dose.

Topics: Adult; Antibiotics, Antineoplastic; Carubicin; Child; Clinical Trials as Topic; Drug Evaluation; Hematopoiesis; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukopenia; Lymphoma; Time Factors

Changes were studied in the value for the nucleolar coefficient as were the percentage of large and compact nucleoli and numbers of Ag-NOR in the peripheral blood of patients with acute myeloblastic leukemia in order that resistant clones might be identified as early as possible. It has been ascertained that within 24 hours of the start of polychemotherapy "7 + 3" leukotic cells respond in different ways to the chemotherapeuticals employed depending on the outcome of the illness.

Topics: Adult; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carubicin; Cell Nucleolus; Cytarabine; Drug Resistance, Neoplasm; Humans; Leukemia, Myeloid, Acute; Lymphocytes; Middle Aged; Prednisolone; Time Factors

Twenty courses of carminomycin were administered to 18 evaluable adult patients with acute leukemia (14 ANLL, 2 ALL, 2 CGL-BC). All but one received daily doses of 6-14 mg/m2 for 5 consecutive days. Two patients older than 60 yr had not prior chemotherapy and the others had refractory or relapsed disease. The median age was 60 yr. Three ANLL patients achieved complete remission for 8, 9 and 9 months respectively, with no maintenance therapy. None of these had proven clinical resistance to daunomycin and/or doxorubicin. Mucositis was dose-related and dose-limiting. Nausea and vomiting were rare. Alopecia was constant. Cardiac arrythmia was ascribed to carminomycin in two patients. One episode of cardiac failure seemed clearly drug-related and recovered with symptomatic treatment. In conclusion, encouraging antileukemic activity was observed with carminomycin in poor-risk patients. At doses up to 12 mg/m2 day X 5, extramedullary toxicity remained acceptable.

Topics: Acute Disease; Adult; Aged; Carubicin; Daunorubicin; Drug Evaluation; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Aziridines; Carubicin; Cyclophosphamide; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Prednisolone; Purines

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Carubicin; Daunorubicin; Drug Evaluation; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Middle Aged; Time Factors

Leukemia cells from 4 acute myelocytic leukemia (AML) and 1 acute lymphocytic leukemia (ALL) patients were incubated with a set of 6 anthracycline agents: Adriamycin (Am), 4'-epi-Adriamycin (4'-epi-Am), daunorubicin (Dm), 4-demethoxy-daunorubicin (4-dDm), carminomycin (Cm) and N-trifluoroacetyl-Am-14-valerate (AD32). Cells were assayed for drug uptake after incubation for 2 h, and for DNA damage and drug retention 4 h later. Uptake and retention patterns were characteristic for each agent and fairly uniform for the different cell populations. In contrast, profiles of the amount of DNA damage produced reflected striking differences in each population of cells. These individual responses raise the possibility that leukemic cells resistant to one anthracycline may yet be sensitive to another.

Topics: Carubicin; Cells, Cultured; Daunorubicin; DNA Repair; DNA, Neoplasm; Doxorubicin; Drug Evaluation; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Prognosis

Topics: Autopsy; Carubicin; Daunorubicin; Drug Evaluation; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute

Topics: Adolescent; Adult; Antineoplastic Agents; Asparaginase; Aziridines; Bone Marrow Transplantation; Carubicin; Cyclophosphamide; Drug Therapy, Combination; Graft Survival; Humans; Immunosuppressive Agents; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Organophosphorus Compounds; Prednisolone; Purines; Thioguanine; Transplantation, Homologous; Vincristine