Codox (Magrath) protocol for Burkitt’s – pro

CODOX-M / IVAC is a combination of several medications used to treat advanced b-cell lymphoma such as Burkitt’s (BL).CODOX-M is given for first and third cycles and includes: Cyclophosphamid, Vincristine, Doxorubicin, Methotrexate. IVACis – given for second and fourth cycles. It consists of: Ifosfamide, Mesna, Etoposide, Cytarabine. These two regimens are normally used in combination with each other and are rarely given alone.

Magrath et al pioneered the use of the CODOX-M/IVAC regimen in children and adults with BL. This regimen incorporates 3 cycles of CODOX-M for patients with low-risk disease (a single extranodal site or completely resected intra-abdominal disease and a normal LDH) and 4 cycles of alternating CODOX-M/IVAC for patients with high-risk disease. CODOX-M/IVAC combines fractionated cyclophosphamide with higher doses of methotrexate (6720 mg/m2) and cytarabine (2000 mg/m2) than administered in the LMB and B-NHL trials, with the exception of LMB 86 in which patients received up to 8000 mg/m2 methotrexate. In the initial publication, 2-year EFS was 85% in children and 100% in adults, with all 20 adult patients achieving a CR.54 In an updated report, CRs were noted in 24 of 26 adult patients treated, with 22 patients alive and disease free, at a median follow-up of 47 months (range, 12-91 months).64 While the results of this study seem remarkable, it is important to recognize that this study involved a relatively young adult patient population, with a median age of 25 years, although 70% of patients had advanced-stage disease by both the St Jude and the Ann Arbor staging systems. In 14 patients with a median age of 47 years, the Magrath regimen produced responses in 86% of patients, with 72% alive and disease free after 21 months of follow-up. In this older group, myelosuppression was universal, and treatment-related deaths were reported in 5 patients.

Codox with IVAC is a well established standard-of-care protocol for agressive lymphomas, especially BL.

Todeschini G, Bonifacio M, Tecchio C, et al. Intensive short-term chemotherapy regimen induces high remission rate (over 90%) and event-free survival both in children and adult patients with advanced sporadic Burkitt lymphoma/leukemia. Am J Hematol. 2012 Jan. 87(1):22-5.

Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L, AIDS Malignancy Consortium..AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9; 126(2):160-6. Epub 2015 May 8.

G. M. Mead , M. R. Sydes , J. Walewski , A. Grigg , C. S. Hatton , P. Norbert , C. Guarnaccia , M. S. Lewis , J. McKendrick , S. P. Stenning , and D. Wright
An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt’s lymphoma: results of United Kingdom Lymphoma Group LY06 study
Ann Oncol 13: 1264-1274.

G. M. Mead, S. L. Barrans, W. Qian, J. Walewski, J. A. Radford, M. Wolf, S. M. Clawson, S. P. Stenning, C. L. Yule, A. S. Jack, et al.
A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial)
Blood, September 15, 2008; 112(6): 2248 – 2260.

K. A. Blum, G. Lozanski, and J. C. Byrd Adult Burkitt leukemia and lymphoma Blood, November 15, 2004; 104(10): 3009 – 3020.

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