A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma.

Abstract

BACKGROUND:

Despite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%.

PATIENTS AND METHODS:

We conducted a phase II trial for newly diagnosed classic BL utilizing liposomal doxorubicin (Adriamycin) in lieu of doxorubicin and incorporating intravenous rituximab (at 500 mg/m(2) twice/cycle) into the CODOX-M/IVAC regimen. Correlative analyses included paired serum and cerebrospinal fluid (CSF) rituximab levels and close examination of cardiac function.

RESULTS:

Among 25 BL patients, the median age was 44 years (23-70) and 4 patients were HIV positive. There were 20 high-risk and 5 low-risk patients. At baseline, 40% of high-risk patients had bone marrow involvement, 35% had bulky disease and 15% had central nervous system involvement. The overall response rate was 100% (complete remission 92%). At 34-month median follow-up, the 2-year PFS and overall survival (OS) rates for all patients were 80% and 84%, respectively (low-risk: both 100%; high-risk: 76% and 81%, respectively). Furthermore, the 2-year PFS, OS, and disease-specific survival (DSS) rates for high-risk, HIV-negative patients were 84%, 89% and 100%, respectively. Adverse events (AEs) appeared to be consistent with prior CODOX-M/IVAC data, although there were several grade 3 cardiac events noted (all declined ejection fraction without clinical symptoms). The mean serum rituximab levels at 24 h after cycles 1 and 3 for patients without relapse were 258 and 306 μg/ml, respectively, versus 131 and 193 μg/ml, respectively, for patients with early progression (P = 0.002 and 0.002, respectively). The mean CSF rituximab levels for all patients were 0.11 and 0.24 μg/ml, respectively, at cycle 1 (24/72 h), which equated to serum:CSF ratios of 0.05% and 0.20%, respectively.

CONCLUSIONS:

The integration of rituximab into CODOX-M/IVAC for adult BL was feasible and tolerable, while changes in cardiac function warrant continued examination. This regimen was associated with excellent survival rates for HIV-negative BL. Further investigation of the predictive value of serum rituximab is needed. Clinicaltrials.gov NCT00392990.

• Authors: A M Evens, K R Carson, J Kolesar, C Nabhan, I Helenowski, N Islam, B Jovanovic, P M Barr, P F Caimi, S A Gregory, L I Gordon
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 24 Issue 12 Pg. 3076-81 (Dec 2013) ISSN: 1569-8041 [Electronic] England
• PMID: 24146219 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• liposomal doxorubicin
• Cytarabine
• Polyethylene Glycols
• Rituximab
• Vincristine
• Etoposide
• Doxorubicin
• Cyclophosphamide
• Ifosfamide
• Methotrexate

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, pharmacokinetics)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Burkitt Lymphoma (drug therapy, mortality)
• Cyclophosphamide (administration & dosage)
• Cytarabine (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage, analogs & derivatives)
• Etoposide (administration & dosage)
• Female
• Humans
• Ifosfamide (administration & dosage)
• Kaplan-Meier Estimate
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Polyethylene Glycols (administration & dosage)
• Rituximab
• Thrombocytopenia (chemically induced)
• Treatment Outcome
• Vincristine (administration & dosage)
• Young Adult