PMID- 20235190
OWN - NLM
STAT- MEDLINE
DCOM- 20100628
LR  - 20240320
IS  - 0008-543X (Print)
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 116
IP  - 11
DP  - 2010 Jun 1
TI  - Durable responses with the metronomic rituximab and thalidomide plus prednisone, 
      etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with 
      recurrent mantle cell lymphoma.
PG  - 2655-64
LID - 10.1002/cncr.25055 [doi]
AB  - BACKGROUND: Targeting the tumor microenvironment and angiogenesis is a novel 
      lymphoma therapeutic strategy. The authors report safety, activity, and 
      angiogenic profiling results with the rituximab and thalidomide plus prednisone, 
      etoposide, procarbazine, and cyclophosphamide (RT-PEPC) regimen in patients with 
      recurrent mantle cell lymphoma (MCL). METHODS: RT-PEPC included induction (Months 
      1-3) of rituximab 4 times weekly, daily thalidomide (50 mg), and PEPC followed by 
      maintenance thalidomide (100 mg), oral PEPC titrated to the neutrophil count, and 
      rituximab every 4 months. Endpoints included safety, efficacy, quality of life 
      (QoL), and translational studies, including tumor angiogenic phenotyping, plasma 
      vascular endothelial growth factor (VEGF), and circulating endothelial cells. 
      RESULTS: Twenty-five patients were enrolled, and 22 were evaluable. The median 
      age was 68 years (range, 52-81 years), 24 patients (96%) had stage III or IV 
      disease, 18 patients (72%) had an International Prognostic Index (IPI) score of 3 
      to 5, and 20 patients (80%) had high-risk Mantle Cell International Prognostic 
      Index (MIPI) scores. Patients had received a median of 2 previous therapies 
      (range, 1-7 previous therapies), and 15 patients (60%) had progressed on 
      bortezomib. At a median follow-up of 38 months, the overall response rate was 73% 
      (complete response [CR]/unconfirmed CR rate, 32%; partial response [PR] rate, 
      41%; n = 22 patients), and the median progression-free survival was 10 months. 
      Four CRs were ongoing (> or =6 months, > or =31 months, > or =48 months, and > or 
      =50 months). Toxicities included grade 1 and 2 fatigue, rash, neuropathy, and 
      cytopenias, including grade 1 and 2 thrombocytopenia (64%) and grade 3 and 4 
      neutropenia (64%). Two thromboses and 5 episodes of grade 3 or 4 infections 
      occurred. QoL was maintained or improved. Correlative studies demonstrated tumor 
      autocrine angiogenic loop (expression of VEGF A and VEGF receptor 1) and 
      heightened angiogenesis and lymphangiogenesis in stroma. Plasma VEGF levels and 
      circulating endothelial cells trended down with treatment. CONCLUSIONS: RT-PEPC 
      had 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.
CI  - (c) 2010 American Cancer Society.
FAU - Ruan, Jia
AU  - Ruan J
AD  - Division of Hematology-Oncology, Center for Lymphoma and Myeloma, Weill Cornell 
      Medical College, New York, New York, USA.
FAU - Martin, Peter
AU  - Martin P
FAU - Coleman, Morton
AU  - Coleman M
FAU - Furman, Richard R
AU  - Furman RR
FAU - Cheung, Ken
AU  - Cheung K
FAU - Faye, Adam
AU  - Faye A
FAU - Elstrom, Rebecca
AU  - Elstrom R
FAU - Lachs, Mark
AU  - Lachs M
FAU - Hajjar, Katherine A
AU  - Hajjar KA
FAU - Leonard, John P
AU  - Leonard JP
LA  - eng
GR  - P01 HL046403/HL/NHLBI NIH HHS/United States
GR  - K08 HL091517/HL/NHLBI NIH HHS/United States
GR  - R01 HL042493-18/HL/NHLBI NIH HHS/United States
GR  - R01 HL090895-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL090895/HL/NHLBI NIH HHS/United States
GR  - K08HL091517/HL/NHLBI NIH HHS/United States
GR  - R01 HL042493/HL/NHLBI NIH HHS/United States
GR  - P01 HL046403-19/HL/NHLBI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 35S93Y190K (Procarbazine)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal
MH  - Antibodies, Monoclonal, Murine-Derived
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Cyclophosphamide/administration & dosage
MH  - Etoposide/administration & dosage
MH  - Female
MH  - Humans
MH  - Lymphoma, Mantle-Cell/*drug therapy/psychology
MH  - Male
MH  - Middle Aged
MH  - Neovascularization, Pathologic
MH  - Prednisone/administration & dosage
MH  - Procarbazine/administration & dosage
MH  - Quality of Life
MH  - Recurrence
MH  - Rituximab
MH  - Thalidomide/administration & dosage
MH  - Treatment Outcome
PMC - PMC3004744
MID - NIHMS257257
EDAT- 2010/03/18 06:00
MHDA- 2010/06/29 06:00
PMCR- 2010/12/20
CRDT- 2010/03/18 06:00
PHST- 2010/03/18 06:00 [entrez]
PHST- 2010/03/18 06:00 [pubmed]
PHST- 2010/06/29 06:00 [medline]
PHST- 2010/12/20 00:00 [pmc-release]
AID - 10.1002/cncr.25055 [doi]
PST - ppublish
SO  - Cancer. 2010 Jun 1;116(11):2655-64. doi: 10.1002/cncr.25055.