carubicin and Leukopenia

KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses the blood-brain barrier where it becomes distributed in brain tissue after intravenous administration. This morpholino anthracycline has been found to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo, We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/m2/day in 3-4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 glioblastoma and 2 anaplastic astrocytomas) demonstrated a complete response (3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was observed in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against malignant glioma with relatively severe, but manageable toxicity. Further assessment of the efficacy and toxicity of KRN8602 against malignant glioma may be worthwhile.

Topics: Adult; Antibiotics, Antineoplastic; Astrocytoma; Brain Neoplasms; Cardiomyopathies; Carubicin; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Glioblastoma; Humans; Leukopenia; Male; Middle Aged; Nausea; Oligodendroglioma; Treatment Outcome; Vomiting

We performed a clinical phase II study of KRN8602, a new anthracycline derivative, for relapsed or recurrent malignant lymphoma. KRN8602 was given at doses of 12-15 mg/m2 for 3 consecutive days, repeating every 3-4 weeks. Among 44 patients entered into the study, 36 were evaluable for safety, and 35 were evaluable for efficacy. The response rate was 18.2% (6PR/33) for non-Hodgkin's lymphoma and 0% (0/2) for Hodgkin's disease. Major toxicities were bone marrow suppression and gastrointestinal toxicity. Leukopenia was observed in 77.8%, thrombocytopenia in 44.4%, hemoglobin decrease in 44.4%, nausea and vomiting in 94.4% and anorexia in 80.6%. However, all toxicities were clinically manageable.

Topics: Anorexia; Antibiotics, Antineoplastic; Carubicin; Drug Administration Schedule; Hodgkin Disease; Humans; Leukopenia; Lymphoma, Non-Hodgkin; Nausea; Thrombocytopenia; Vomiting

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.

Topics: Adult; Aged; Alopecia; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Female; Follow-Up Studies; Heart Diseases; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Metastasis; Random Allocation; Vomiting

Topics: Adult; Aged; Bleomycin; Carcinoma, Squamous Cell; Carubicin; Clinical Trials as Topic; Daunorubicin; Humans; Leukopenia; Lung Neoplasms; Male; Methotrexate; Middle Aged; Nausea; Vomiting

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Leukopenia; Middle Aged; Time Factors

Topics: Antibiotics, Antineoplastic; Carubicin; Clinical Trials as Topic; Drug Evaluation; Humans; Leukopenia; Sarcoma; Soft Tissue Neoplasms

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

KRN 8602 is a new antineoplastic drug with the chemical structure, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. This drug was developed in an attempt to improve the clinical efficacy of currently used anthracyclines. In preclinical studies, KRN 8602 has been shown to produce less cardiotoxicity and alopecia, yet has comparable antitumor effects to adriamycin. In addition, KRN 8602 has shown antitumor effects on adriamycin-resistant tumors. A phase I clinical study was undertaken to determine the toxicity of KRN 8602 given as a single i.v. dose. Toxicity evaluation included CBC with differentials, platelet counts, SMA chemistry profile, EKG, urinalysis, plain chest X-ray and physical examination. Myelosuppression was the major side effect noted with leukopenia, and especially neutropenia, being dose-limiting. The degree of WBC suppression was dose-related and MTD appears to be 30 mg/m2. Nausea and vomiting were observed in cases who had received more than 10 mg/m2. No patient had alopecia. No obvious cardiotoxicity in this study. Maximum total cumulative dose of KRN 8602 was 450 mg/m2. Further observation is necessary to confirm this point. In this study of 10 cases, one breast carcinoma with bilateral lung metastasis revealed definite regression of metastasis for more than 18 months with this agent alone. This patient had previous chemo- and hormone therapy, containing adriamycin. The above preliminary phase I clinical study suggests strongly the usefulness of KRN 8602, and further investigations are indicated.

Topics: Adult; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Drug Evaluation; Female; Humans; Injections, Intravenous; Leukopenia; Male; Middle Aged; Nausea; Stomach Neoplasms; Vomiting

Phase I clinical trial of a new semi-synthetic morpholino anthracycline derivative, KRN8602, was performed. Sixteen patients with advanced malignant neoplasms refractory to standard chemotherapies received 27 courses at doses ranging from 1.5 mg/m2/day to 18 mg/m2/day by bolus injection for three consecutive days. The dose limiting toxicity was leukopenia, and a maximally tolerated dose was 18 mg/m2/day (day 1-3). The recommended dose and schedule for a phase II study is determined to be 12 mg/m2/day for three consecutive days at 3-4 weeks intervals. Among non-hematologic toxicities, nausea and vomiting were severe, but stomatitis and alopecia were rarely observed. Clinical signs of cardiotoxicity were not seen.

Topics: Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carubicin; Drug Evaluation; Female; Hodgkin Disease; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Thrombocytopenia

Topics: Adolescent; Adult; Aged; Carubicin; Daunorubicin; Drug Administration Schedule; Drug Evaluation; Humans; Injections, Intravenous; Leukopenia; Middle Aged; Neoplasms; United States

Topics: Adult; Aged; Carubicin; Daunorubicin; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasms; Thrombocytopenia

Topics: Alanine Transaminase; Anemia, Aplastic; Animals; Antibiotics, Antineoplastic; Aspartate Aminotransferases; Bilirubin; Blood Glucose; Bone Marrow Cells; Carubicin; Cell Count; Chemical and Drug Induced Liver Injury; Dogs; Injections, Intravenous; Leukopenia; Lymph Nodes; Lymphatic Diseases; Plasma Cells; Potassium; Reticulocytes; Sodium; Spleen; Time Factors; Urea