title: Protease inhibitors potentiate chemotherapy-induced neutropenia.
abstract: Pharmacokinetic interactions between chemotherapy and highly active antiretroviral therapy (HAART) are described, but there are few data on their clinical relevance. Patients with systemic AIDS-related non-Hodgkin lymphoma (ARL) were treated with concomitant HAART and infusional cyclophosphamide-doxorubicin-etoposide (CDE) chemotherapy. We compared neutropenia according to whether patients received protease inhibitor (PI)-based HAART or non-PI regimens. Differences in survival, response rates, immunologic parameters, and virologic parameters were also investigated. The day-10 (Mann-Whitney U test; P = .012) and day-14 (P = .025) neutrophil counts were significantly lower in patients receiving PIs, though there were no differences in the number of days of granulocyte colony-stimulating factor (G-CSF) administered between groups (P = .16). Grade 3 or 4 infections requiring hospitalization were recorded for a total of 58 (31%) of 190 cycles of CDE: 23 (48%) of 48 when prescribed PIs and 35 (25%) of 142 with concomitant PI-sparing HAART (chi(2) test; P = .0025). There were no statistically significant differences in the response rates, relapse-free survival, or disease-free survival between patients receiving PIs and those not receiving PIs. PI-based HAART appears to significantly potentiate the myelotoxicity of CDE chemotherapy. This potentiation may be a consequence of microsomal enzyme inhibition reducing the metabolism of cytotoxics in this regimen.
authors.affiliation: Department of Oncology, The Chelsea and Westminster Hospital, 369 Fulham Rd, London SW10 9NH, United Kingdom. m.bower@imperial.ac.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Bower
authors.forename: Neil
authors.initials: N
authors.lastname: McCall-Peat
authors.forename: Natalie
authors.initials: N
authors.lastname: Ryan
authors.forename: Liz
authors.initials: L
authors.lastname: Davies
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Young
authors.forename: Srirupa
authors.initials: S
authors.lastname: Gupta
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007239:Infections / Q000139:chemically induced; D007700:Kinetics; D016483:Lymphoma, AIDS-Related / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000633:toxicity; D009503:Neutropenia / Q000139:chemically induced*; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019653:Myeloablative Agonists; D011480:Protease Inhibitors; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide