{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:30:55Z","timestamp":1762101055914,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2010,7,27]],"date-time":"2010-07-27T00:00:00Z","timestamp":1280188800000},"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":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Bortezomib has preclinical and clinical in B\u2010cell lymphomas, both alone and in combination with other agents. A phase 1 evaluation was conducted of bortezomib with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R\u2010CHOP) in patients with untreated diffuse large B\u2010cell lymphoma (DLBCL) or mantle cell lymphoma (MCL).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Twenty patients (16 with DLBCL and 4 with MCL) with a median age of 66 years (range, 29\u201084 years) were enrolled. Eleven subjects (55%) had an elevated lactate dehydrogenase level, and 10 patients (50%) had International Prognostic Index scores of 3 to 5. Standard R\u2010CHOP was administered on a 21\u2010day cycle for 6 cycles, with 1 of 3 dose levels of bortezomib (0.7 mg\/m<jats:sup>2<\/jats:sup> [n = 4 patients], 1.0 mg\/m<jats:sup>2<\/jats:sup> [n = 9 patients], or 1.3 mg\/m<jats:sup>2<\/jats:sup> [n = 7 patients]) administered on Days 1 and 4 of each cycle.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>The maximum tolerated dose of bortezomib with R\u2010CHOP was not reached, and the 1.3\u2010mg\/m<jats:sup>2<\/jats:sup> dose level had acceptable tolerability. A dose\u2010limiting toxicity (pulmonary) was only observed in 1 patient receiving 1.0 mg\/m<jats:sup>2<\/jats:sup> of bortezomib. Neuropathy occurred in 13 patients (65%), but was mostly grade 1 (45%) and reached grade 3 in only 1 patient (all toxicities were graded using the Common Terminology Criteria for Adverse Events, version 3.0). Grade 4 hematologic toxicity occurred in 7 patients (35%). Of 19 evaluable patients, all responded, with 18 (95%) cases of complete response\/complete response unconfirmed achieved and 1 (5%) partial response reported. At a median follow\u2010up of 56 months, overall survival at 4 years was 75% and progression\u2010free survival was 58%.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Bortezomib at a dose of 1.3 mg\/m<jats:sup>2<\/jats:sup> twice per cycle can be added to R\u2010CHOP chemotherapy with acceptable toxicity. Multi\u2010institutional and cooperative group follow\u2010up studies of this regimen are currently ongoing. Cancer 2010. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25509","type":"journal-article","created":{"date-parts":[[2010,7,27]],"date-time":"2010-07-27T19:50:40Z","timestamp":1280260240000},"page":"5432-5439","source":"Crossref","is-referenced-by-count":36,"title":["Phase 1 trial of bortezomib plus R\u2010CHOP in previously untreated patients with aggressive non\u2010Hodgkin lymphoma"],"prefix":"10.1002","volume":"116","author":[{"given":"Richard R.","family":"Furman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Kuen K.","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie M.","family":"Vose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann S.","family":"LaCasce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Elstrom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morton","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,11,29]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1589"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2006.s.002"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.015"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.4.1075.bloodjournal8541075"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.09.131"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.2.389"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200201243460411"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.1003"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(06)70664-7"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.08.133"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.5.1288"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200620010-00002"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21805"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802885"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012914"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.12.1861"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.1.88"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3130"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15671"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl316"},{"key":"e_1_2_7_22_2","first-page":"126","article-title":"Active combination therapy of Bortezomib and Rituximab in an in vitro and in vivo DLBCL model [abstract]","volume":"45","author":"De Vos S","year":"2004","journal-title":"AACR Meeting Abstracts."},{"key":"e_1_2_7_23_2","doi-asserted-by":"crossref","DOI":"10.1200\/jco.2006.24.18_suppl.17522","article-title":"Marked activity of bortezomib, rituximab, and dexamethasone (BORID) in heavily pretreated patients with mantle cell lymphoma [abstract]","volume":"24","author":"Drach J","year":"2006","journal-title":"J Clin Oncol."},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.108"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn656"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.050"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.6789"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07466.x"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-01-199679"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2000.01177.x"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2002.00671.x"},{"key":"e_1_2_7_32_2","unstructured":"Common Terminology Criteria for Adverse Events v3.0 (CTCAE). 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