{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T14:11:05Z","timestamp":1784988665183,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,3,16]],"date-time":"2010-03-16T00:00:00Z","timestamp":1268697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>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\u2010PEPC) regimen in patients with recurrent mantle cell lymphoma (MCL).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>RT\u2010PEPC included induction (Months 1\u20103) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Twenty\u2010five patients were enrolled, and 22 were evaluable. The median age was 68 years (range, 52\u201081 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\u2010risk Mantle Cell International Prognostic Index (MIPI) scores. Patients had received a median of 2 previous therapies (range, 1\u20107 previous therapies), and 15 patients (60%) had progressed on bortezomib. At a median follow\u2010up 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\u2010free survival was 10 months. Four CRs were ongoing (\u22656 months, \u226531 months, \u226548 months, and \u226550 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>RT\u2010PEPC had significant and durable activity in MCL with manageable toxicity and maintained QoL. Novel, low\u2010intensity approaches warrant further evaluation, potentially as initial therapy in elderly patients. Cancer 2010. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25055","type":"journal-article","created":{"date-parts":[[2010,3,16]],"date-time":"2010-03-16T12:00:42Z","timestamp":1268740842000},"page":"2655-2664","source":"Crossref","is-referenced-by-count":50,"title":["Durable responses with the metronomic rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with recurrent mantle cell lymphoma"],"prefix":"10.1002","volume":"116","author":[{"given":"Jia","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morton","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Furman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Faye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Elstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Hajjar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,3,16]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1182\/blood.V85.4.1075.bloodjournal8541075","article-title":"A clinical analysis of 2 indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa\u2010associated lymphoid tissue and monocytoid B\u2010cell subcategories): a Southwest Oncology Group study","volume":"85","author":"Fisher RI","year":"1995","journal-title":"Blood."},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.5.1288"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.08.133"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.1825"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-3883"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.8435"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.9665"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.13.466"},{"issue":"20","key":"e_1_2_7_10_2","article-title":"Phase III study of patients with relapsed, refractory mantle cell lymphoma treated with temsirolimus compared with investigator's choice [abstract]","volume":"26","author":"Hess G","year":"2008","journal-title":"J Clin Oncol."},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.3429"},{"issue":"20","key":"e_1_2_7_12_2","article-title":"International study of lenalidomide in relapsed\/refractory aggressive non\u2010Hodgkin's lymphoma [abstract]","volume":"26","author":"Czuczman MS","year":"2008","journal-title":"J Clin Oncol."},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07626.x"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701837330"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1091"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-016725"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.4.1244"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.3.570"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1369"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1323"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23422"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0474"},{"key":"e_1_2_7_23_2","first-page":"4342","article-title":"Maximum tolerable dose and low\u2010dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells","volume":"63","author":"Bertolini F","year":"2003","journal-title":"Cancer Res."},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127592"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4570"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190902856808"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2530"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.25055","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.25055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:42:19Z","timestamp":1760272939000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.25055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,16]]},"references-count":26,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2010,6]]}},"alternative-id":["10.1002\/cncr.25055"],"URL":"https:\/\/doi.org\/10.1002\/cncr.25055","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,16]]}}}