Feasibility and pharmacokinetic study of infusional dexrazoxane and dose-intensive doxorubicin administered concurrently over 96 h for the treatment of advanced malignancies

Dexrazoxane administration prior to short infusion doxorubicin prevents anthracycline-related heart damage. Since delivery of doxorubicin by 96-h continuous intravenous infusion also reduces cardiac injury, we studied delivering dexrazoxane and doxorubicin concomitantly by prolonged intravenous infu...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2004-09, Vol.54 (3), p.241-248
Main Authors: CHOW, Warren A, SYNOLD, Timothy W, MORGAN, Robert J, RASCHKO, James, SHIBATA, Stephen, SOMLO, George, TWARDOWSKI, Przemyslaw, YUN YEN, DOROSHOW, James H, TETEF, Merry L, LONGMATE, Jeffrey, FRANKEL, Paul, LAWRENCE, Joyce, AL-KHADIMI, Zaid, LEONG, Lucille, LIM, Dean, MARGOLIN, Kim
Format: Article
Language:English
Subjects:
Adult
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - adverse effects
Antineoplastic agents
Biological and medical sciences
Cardiovascular Agents - administration & dosage
Cardiovascular Agents - pharmacokinetics
Doxorubicin - administration & dosage
Doxorubicin - adverse effects
Drug Administration Schedule
Drug Therapy, Combination
Female
Granulocyte Colony-Stimulating Factor - administration & dosage
Heart Failure - chemically induced
Heart Failure - prevention & control
Humans
Infusions, Intravenous
Levofloxacin
Male
Medical sciences
Middle Aged
Neoplasms - drug therapy
Neutropenia - chemically induced
Ofloxacin - administration & dosage
Pharmacology. Drug treatments
Razoxane - administration & dosage
Razoxane - pharmacokinetics
Sarcoma - drug therapy
Sepsis
Treatment Outcome
Tumors
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Summary:Dexrazoxane administration prior to short infusion doxorubicin prevents anthracycline-related heart damage. Since delivery of doxorubicin by 96-h continuous intravenous infusion also reduces cardiac injury, we studied delivering dexrazoxane and doxorubicin concomitantly by prolonged intravenous infusion. Patients with advanced malignancies received tandem cycles of concurrent 96-h infusions of dexrazoxane 500 mg/m2 and doxorubicin 165 mg/m2, and 24 h after completion of chemotherapy, granulocyte-colony stimulating factor (5 microg/kg) and oral levofloxacin (500 mg) were administered daily until the white blood cell count reached 10,000 microl(-1). Plasma samples were analyzed for dexrazoxane and doxorubicin concentrations. Ten patients were enrolled; eight patients had measurable disease. Two partial responses were observed in patients with soft-tissue sarcoma. The median number of days of granulocytopenia (
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-004-0803-4