carubicin and Anorexia

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

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

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