title: Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials.
abstract: Evidence suggests that infusional therapy is a more effective means for administering cytotoxic therapy than intravenous bolus therapy for lymphoma and offers greater potential for therapeutic synergy with rituximab, which has a long half-life. We pooled the results of 3 prospective phase 2 trials evaluating rituximab in combination with 96-hour infusion of cyclophosphamide (187.5-200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2 per day) (R-CDE) plus granulocyte-colony-stimulating factor (G-CSF) in 74 patients with HIV-associated, B-cell non-Hodgkin lymphoma, of whom 56 (76%) patients received concurrent highly active antiretroviral therapy (HAART). The complete remission (CR) rate was 70% (95% confidence interval [CI], 59%-81%), and the estimated 2-year failure-free survival and overall survival rates were 59% (95% CI, 47%-71%) and 64% (95% CI, 52%-76%), respectively. Ten (14%) patients had opportunistic infections during or within 3 months of the end of R-CDE, and 17 (23%) patients developed nonopportunistic infections after that time. Six (8%) patients died because of infection; 2 (3%) of those infections were bacterial sepsis during R-CDE, and 4 (5%) were opportunistic infections that occurred between 2 and 8 months after the completion of R-CDE. R-CDE produced a 70% CR rate and a 59% 2-year failure-free survival rate in patients with HIV-associated lymphoma. Consistent with other reports, adding rituximab to cytotoxic therapy in this population may increase the risk for life-threatening infection. Further studies evaluating rituximab in combination with infusional chemotherapy are warranted, but caution is advised.
authors.affiliation: Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, 33081, Aviano (PN) Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Spina
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Simonelli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Michieli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Ezio
authors.initials: E
authors.lastname: Nigra
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Berretta
authors.forename: Chiara
authors.initials: C
authors.lastname: Cattaneo
authors.forename: Armin C
authors.initials: AC
authors.lastname: Rieger
authors.forename: Emanuela
authors.initials: E
authors.lastname: Vaccher
authors.forename: Umberto
authors.initials: U
authors.lastname: Tirelli
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D023241:Antiretroviral Therapy, Highly Active; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007239:Infections; D007262:Infusions, Intravenous; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy* / Q000401:mortality; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections; D012074:Remission Induction; D000069283:Rituximab; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016179:Granulocyte Colony-Stimulating Factor; D000069283:Rituximab; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide