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.
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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)
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Chemical References |
- Antibodies, Monoclonal, Murine-Derived
- liposomal doxorubicin
- Cytarabine
- Polyethylene Glycols
- Rituximab
- Vincristine
- Etoposide
- Doxorubicin
- Cyclophosphamide
- Ifosfamide
- Methotrexate
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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
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