title: Identification of pharmacogenomic markers of clinical efficacy in a dose-dense therapy regimen (R-CHOP14) in diffuse large B-cell lymphoma.
abstract: About 60% of patients with diffuse large B-cell lymphoma (DLBCL) may be cured by primary chemotherapy with an R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen. Most of the rest will die of the disease, mainly due to the occurrence of tumor drug resistance. Many efforts have been made to explain the molecular mechanisms of drug resistance in patients with cancer, including those with DLBCL. This exploratory study was designed to correlate the mRNA expression levels of candidate genes mainly involved in the doxorubicin pathway (ABCB1, GSTP1, TOPO2α, BCL2, PKCβII) with the outcome of 54 patients with DLBCL undergoing a dose-dense R-CHOP regimen. After multivariate analysis, high GSTP1 (p = 0.003) and TOPO2α (p = 0.02) gene expressions were associated with shorter overall survival and progression-free survival, respectively, suggesting that these genes may represent an unfavorable prognostic factor in the case of R-CHOP treatment. These biomarkers may be useful for selecting patients eligible for personalized chemotherapy after validation in an independent set.
authors.affiliation: Sezione di Farmacologia Clinica e Oncologia, Dipartimento di Scienze della Salute, Università degli Studi di Firenze , Florence , Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Nobili
authors.forename: Cristina
authors.initials: C
authors.lastname: Napoli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Puccini
authors.forename: Ida
authors.initials: I
authors.lastname: Landini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Perrone
authors.forename: Marco
authors.initials: M
authors.lastname: Brugia
authors.forename: Gemma
authors.initials: G
authors.lastname: Benelli
authors.forename: Morena
authors.initials: M
authors.lastname: Doria
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martelli
authors.forename: Erica
authors.initials: E
authors.lastname: Finolezzi
authors.forename: Alice
authors.initials: A
authors.lastname: Di Rocco
authors.forename: Emanuele
authors.initials: E
authors.lastname: Del Fava
authors.forename: Luigi
authors.initials: L
authors.lastname: Rigacci
authors.forename: Simonetta
authors.initials: S
authors.lastname: Di Lollo
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D057285:Precision Medicine; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Dose-dense R-CHOP; diffuse large B-cell lymphoma; gene expression; personalized therapy