mercaptopurine and pirarubicin

This study was conducted as the first clinical trial by Japan Association of Childhood Leukemia Study to improve the outcome of B-cell acute lymphoblastic leukemia and explore a less toxic reinduction block.. From 1997 to 2002, 563 patients with B-cell acute lymphoblastic leukemia aged 1 to 15 years were enrolled. The patients were assigned into 4 risk groups (standard, intermediate, high, or extremely high risk) and treated with regimens intensified according to the risk. Two randomized trials were conducted to compare 2 regimens with and without a 3-week reinduction therapy in the standard-risk group, and to compare the efficacy of pirarubicin with daunorubicin in the intermediate-risk and high-risk groups. Prophylactic cranial irradiation was restricted in patients with high or extremely high risk.. The event-free survival (EFS) rate at 10 years for all patients was 77.0%. Those in the standard-risk to extremely high-risk groups were 79.3%, 72.5%, 71.7%, and 66.3%, respectively. The 15-week induction/consolidation not followed by reinduction produced 76.4% of the EFS at 10 years comparable with the regimen with reinduction therapy. Pirarubicin at 25 mg/m administered 11 times throughout the treatment produced the EFS comparable with daunorubicin at 30 mg/m.. The trial produced high survival rates in NCI-HR patients, although the outcomes in NCI-SR patients were not satisfactory possibly due to less intensive central nervous system-directed therapy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Consolidation Chemotherapy; Cranial Irradiation; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Humans; Hydrocortisone; Infant; Japan; Maintenance Chemotherapy; Male; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Remission Induction; Risk; Survival Rate; Treatment Outcome; Vincristine

Topics: Antimetabolites, Antineoplastic; Brain Ischemia; Cytarabine; Deglutition Disorders; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Doxorubicin; Dysarthria; Hemiplegia; Humans; Hydrocortisone; Injections; Leukoencephalopathies; Magnetic Resonance Angiography; Male; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Young Adult

We have examined the therapeutic effects of combination therapy of pirarubicin ((2"R)-4'-O-tetrahydropyranyladriamycin, THP) with various antitumor agents against P388 murine leukemia. THP showed a high antitumor activity in combination with various antitumor drugs, especially with cyclophosphamide (CPM), cisplatin (CDDP), mitomycin C (MMC), enocitabine (BHAC), vindesine (VDS) or methotrexate (MTX). The effects of combination therapy depended on the order of administration of THP and combined drugs. THP-preceding treatment gave more synergistic effects in combination with 5-fluorouracil (5-FU) or MTX. THP-preceding or simultaneous treatment with etoposide (ETP) indicated the higher synergistic activity than ETP-preceding one. Moreover, THP showed much higher synergistic effects in any order of the combination with CPM, CDDP, MMC, BHAC, VDS or MTX. These results suggest that THP possesses a therapeutic usefulness clinically in combination with various antitumor drugs, if the selection of drugs combined with THP and the order of administration are suitable.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Screening Assays, Antitumor; Fluorouracil; Leukemia P388; Male; Mercaptopurine; Methotrexate; Mice; Mice, Inbred BALB C; Mitomycin; Peplomycin; Vindesine