title: High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant mesothelioma: a phase II study-Cancer and Leukemia Group B 9631.
abstract: Doxorubicin is the most widely studied agent for the treatment of malignant mesothelioma. In conventional doses, the response rate is approximately 17%. Higher dose doxorubicin has been successfully employed in other tumor types. Dexrazoxane has been demonstrated to reduce the cardiac toxicity associated with long term, chronic use of doxorubicin. Based upon phase I data generated by the Cancer and Leukemia Group B (CALGB) indicating that doxorubicin at a dose of 120 mg/m(2) when combined with dexrazoxane and GM-CSF could be safely administered, the CALGB undertook a phase II study of high-dose doxorubicin in patients with malignant mesothelioma. Toxicity was excessive, necessitating protocol modification and ultimately protocol termination. There were no objective responses observed. We conclude that high-dose doxorubicin administered with dexrazoxane is unacceptably toxic in this patient population.
authors.affiliation: Division of Hematology/Medical Oncology, MS217, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA. mkosty@scripps.edu
authors.forename: M P
authors.initials: MP
authors.lastname: Kosty
authors.forename: J E
authors.initials: JE
authors.lastname: Herndon
authors.forename: N J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: H L
authors.initials: HL
authors.lastname: Kindler
authors.forename: M R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011929:Razoxane / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D011929:Razoxane; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor