title: Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy.
abstract: Ten percent of newly diagnosed myeloma patients treated with any type of chemotherapy develop deep venous thrombosis (DVT). Thalidomide has proven activity in refractory multiple myeloma (MM), and although single-agent thalidomide has minimal prothrombogenic activity, its combination with cytotoxic chemotherapy is associated with a significantly increased risk of DVT. We analyzed the incidence of DVT in 232 MM patients who received a combination of chemotherapy and thalidomide on 2 protocols that differed only by the inclusion of doxorubicin in one. DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide) was offered to patients with preceding standard dose therapy, but no prior autotransplantation, while DCEP-T (dexamethasone/cyclophosphamide/etoposide/cisplatin/thalidomide) was administered for relapse after transplantation. If there were signs or symptoms suggestive of DVT, patients received additional investigations, including Doppler ultrasonography, followed by venography if indicated. Only patients on DT-PACE but not DCEP-T experienced an increased incidence of DVT. A statistical association between the incidence of DVT and combination chemotherapy including doxorubicin (P =.02) was observed; this association was confirmed on multivariate analysis. MM patients treated with thalidomide and doxorubicin have a high risk of developing DVT.
authors.affiliation: Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, USA. zangarimaurizio@uams.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Eric
authors.initials: E
authors.lastname: Siegel
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Fariba
authors.initials: F
authors.lastname: Saghafifar
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.forename: Christopher
authors.initials: C
authors.lastname: Morris
authors.forename: Louis
authors.initials: L
authors.lastname: Fink
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001853:Bone Marrow / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects*; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D001613:beta 2-Microglobulin; D013792:Thalidomide; D004317:Doxorubicin