title: Excessive neurotoxicity with ABVD when combined with protease inhibitor-based antiretroviral therapy in the treatment of AIDS-related Hodgkin lymphoma.
abstract: Hodgkin lymphoma (HL) is the second most common non-AIDS-defining malignancy among persons infected with HIV, and its incidence might be increasing in the current era of combination antiretroviral therapy (cART). With the immune reconstitution afforded by cART, most patients are now able to tolerate the standard-dose chemotherapies administered to immunocompetent individuals with HL, such as ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine). Antiretroviral therapy is commonly prescribed concomitantly with chemotherapy in the treatment of AIDS-related malignancies. However, little is known about the pharmacokinetic consequences of combined therapy. In particular, the potential for excessive vinca alkaloid-associated toxicity is significant, given the metabolism of drugs such as vinblastine by the 3A4 isoenzyme of the cytochrome P450 system and the inhibition of this isoenzyme by protease inhibitors. We report 3 patients who experienced severe vinblastine-associated neurotoxicity during concomitant treatment with ritonavirboosted antiretrovirals. The implications for the treatment of patients with HL in the current era of cART are discussed.
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Hematology/Oncology, Toronto, Ontario, Canada. matthew.cheung@sunnybrook.ca
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cheung
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Hicks
authors.forename: Heather A
authors.initials: HA
authors.lastname: Leitch
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D015994:Incidence; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000188:drug therapy; D011480:Protease Inhibitors / Q000627:therapeutic use; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D011480:Protease Inhibitors; D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin