title: AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma.
abstract: The toxicity of dose-intensive regimens used for Burkitt lymphoma prompted modification of cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for HIV-positive patients. We added rituximab, reduced and/or rescheduled cyclophosphamide and methotrexate, capped vincristine, and used combination intrathecal chemotherapy. Antibiotic prophylaxis and growth factor support were required; highly active antiretroviral therapy (HAART) was discretionary. Thirteen AIDS Malignancy Consortium centers enrolled 34 patients from 2007 to 2010. Median age was 42 years (range, 19-55 years), 32 of 34 patients were high risk, 74% had stage III to IV BL and CD4 count of 195 cells per μL (range, 0-721 cells per μL), and 5 patients (15%) had CD4 <100 cells per μL. Twenty-six patients were receiving HAART; viral load was <100 copies per mL in 12 patients. Twenty-seven patients had at least one grade 3 to 5 toxicity, including 20 hematologic, 14 infectious, and 6 metabolic. None had grade 3 to 4 mucositis. Five patients did not complete treatments because of adverse events. Eleven patients died, including 1 treatment-related and 8 disease-related deaths. The 1-year progression-free survival was 69% (95% confidence interval [CI], 51%-82%) and overall survival was 72% (95% CI, 53%-84%); 2-year overall survival was 69% (95% CI, 50%-82%). Modifications of the CODOX-M/IVAC regimen resulted in a grade 3 to 4 toxicity rate of 79%, which was lower than that in the parent regimen (100%), without grade 3 to 4 mucositis. Despite a 68% protocol completion rate, the 1-year survival rate compares favorably with 2 studies that excluded HIV-positive patients. This trial was registered at http://clinicaltrials.gov as #NCT00392834.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical Center, New York, NY;
authors.forename: Ariela
authors.identifier: http://orcid.org/0000-0002-3001-4898
authors.initials: A
authors.lastname: Noy
authors.affiliation: University of Arkansas Medical Center, Little Rock, AR;
authors.forename: Jeannette Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY;
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD;
authors.forename: Richard
authors.initials: R
authors.lastname: Ambinder
authors.affiliation: Division of Hematology, Ohio State Medical Center, Columbus, OH;
authors.forename: Robert
authors.initials: R
authors.lastname: Baiocchi
authors.affiliation: University of California San Diego, Moores Cancer Center, La Jolla, CA;
authors.forename: Erin
authors.initials: E
authors.lastname: Reid
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, MO; and.
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, MO; and.
authors.forename: Nina
authors.initials: N
authors.lastname: Wagner-Johnston
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D015497:HIV-1; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide; D008727:Methotrexate