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1.  Durable Responses with the Metronomic Regimen RT-PEPC in Elderly Patients with Recurrent Mantle Cell Lymphoma 
Cancer  2010;116(11):2655-2664.
BACKGROUND
Targeting the tumor microenvironment and angiogenesis is a novel lymphoma therapeutic strategy. We report safety, activity and angiogenic profiling with the RT-PEPC regimen (rituximab with thalidomide, and prednisone, etoposide, procarbazine and cyclophosphamide) in recurrent mantle cell lymphoma (MCL).
METHODS
RT-PEPC includes induction (months 1–3) of weekly rituximab × 4, daily thalidomide (50 mg) and PEPC, then maintenance thalidomide (100 mg), oral PEPC titrated to neutrophil count, and rituximab every 4 months. Endpoints included safety, efficacy, quality of life (QoL), and translational studies including tumor angiogenic phenotyping, plasma VEGF and circulating endothelial cells.
RESULTS
Twenty-five pts were enrolled (22 evaluable) with median age 68 yrs (range 52–81), 24 (96%) stage III/IV, 18 (72%) IPI 3–5, 20 (80%) high risk MIPI, median 2 prior therapies (range 1–7), and 15 (60%) bortezomib progressors. At a median follow-up of 38 months, ORR was 73% (32% CR/CRu, 41% PR, n=22) and median PFS 10 months. Four CRs are ongoing (6+, 31+, 48+ and 50+ months). Toxicities included grade 1–2 fatigue, rash, neuropathy and cytopenias including grade 1–2 thrombocytopenia (64%) and grade 3–4 neutropenia (64%). Two thromboses and 5 grade 3–4 infections occurred. QoL was maintained or improved. Correlative studies demonstrated tumor autocrine angiogenic loop (expression of VEGFA and VEGFR1) and heightened angiogenesis and lymphangiogenesis in stroma. Plasma VEGF and circulating endothelial cells trended down with treatment.
CONCLUSIONS
RT-PEPC has significant and durable activity in MCL, with manageable toxicity and maintained QoL. Novel low-intensity approaches warrant further evaluation, potentially as initial therapy in elderly patients.
doi:10.1002/cncr.25055
PMCID: PMC3004744  PMID: 20235190

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