The anthracycline group of compounds is extensively used in current cancer chemotherapy regimens and is classified as topoisomerase II inhibitor. However, previous work has shown that doxorubicin can be activated to form DNA adducts in the presence of formaldehyde-releasing prodrugs and that this leads to apoptosis independently of topoisomerase II-mediated damage. To determine which anthracycl...

BACKGROUND AND OBJECTIVE The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C ...

The role of the immune system in response to chemotherapeutic agents remains elusive. The interpatient variability observed in immune and chemotherapeutic cytotoxic responses is likely, at least in part, due to complex genetic differences. Through the use of a panel of genetically diverse mouse inbred strains, we developed a drug screening platform aimed at identifying genes underlying these ch...

Overall survival (OS) with acute myeloid leukemia (AML) remains poor. Determining prognostic factors will help in selecting patients for appropriate treatments. Our aim was to determine whether the level of drug-induced apoptosis (chemosensitivity) demonstrated by the microculture-kinetic drug-induced apoptosis (MiCK) assay significantly predicted outcomes after standard AML induction therapy. ...

We conducted a phase I and pharmacokinetic study of i.v. idarubicin, a new anthracycline analogue, in 42 évaluable children 1-19 years old. Twenty-seven had leukemia and 15 had various solid tumors. The drug »asadministered in escalating doses of 10 to 40 mg/m2/course in 3 equal fractions over 3 consecutive days at 14to 21-day intervals. Myelosuppression and mucositis were the limiting toxici...

Many of the experimental approaches used in the search for new targeted drug delivery systems ignore the disseminated nature of metastatic disease; the development of more relevant tumor models is therefore a priority. A reproducible and tumor-specific model has been generated by inoculating (C57BL/6 x BALB/c) F1 (Ly-2.2+) mice i.v. with the Ly-2.1+ murine ITT(1) 75NS E3 thymic lymphoma (E3). A...

Aim: Disease free survival rate for acute myeloid leukemia (AML) is still below 50% for the last 30 years. Our objective was to compare the results of two different dosages of idarubicin (12 mg/m2 versus 8 mg/ m2) therapy for newly diagnosed AML patients. Method: Sixty eight patients with AML were treated between February, 1998 and January, 2005. We designed two therapy groups comprising of 12 ...

BACKGROUND AND OBJECTIVE Idarubicin, an anthracycline analogue, is active in non-Hodgkin's lymphoma. This study evaluates the efficacy and toxicity of a combination of idarubicin, etoposide and intermediate-dose cytarabine (IVA) in unfavorable lymphoma in relapse or resistant to prior doxorubicin- or novantrone-based regimens. DESIGN AND METHODS Thirty patients with relapsing or resistant unf...