{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T18:21:58Z","timestamp":1759602118483},"reference-count":42,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"33","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2009,11,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> This study evaluated safety and efficacy of chemotherapy (gemcitabine plus capecitabine) plus bevacizumab\/erlotinib in advanced pancreatic cancer because dual epidermal growth factor receptor\/vascular endothelial growth factor blockade has a rational biologic basis in this malignancy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients with untreated, unresectable, locally advanced or metastatic pancreatic carcinoma were enrolled onto one of the following four sequential dose levels (DLs) of escalating capecitabine doses (days 1 to 21): DL1, 910 mg\/m<jats:sup>2<\/jats:sup>; DL2, 1,160 mg\/m<jats:sup>2<\/jats:sup>; DL3, 1,400 mg\/m<jats:sup>2<\/jats:sup>; or DL4, 1,660 mg\/m<jats:sup>2<\/jats:sup>. Doses of coadministered gemcitabine (1,000 mg\/m<jats:sup>2<\/jats:sup> on days 1, 8, and 15), bevacizumab (5 mg\/kg on days 1 and 15), and erlotinib (100 mg\/d) every 28 days (up to six cycles) were fixed. Using a 3+3 study design, dose-limiting toxicity (DLT) was assessed in cycle 1. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Twenty assessable patients were enrolled (DL1, n = 8; DL2, n = 3; DL3, n = 6; and DL4, n = 3); 97 cycles were administered. Median age was 63 years (range, 33 to 77 years), and male-to-female ratio was 10:10. Performance status was 0 and 1 in two and 17 patients, respectively; and nine and 11 patients had locally advanced and metastatic disease, respectively. DLT occurred in one patient at DL1 (grade 3 epistaxis) and two patients at DL4 (grade 3 diarrhea and grade 3 skin rash &gt; 7 days). Common grade 3 and 4 toxicities (10% to 20%) were diarrhea, hand-foot syndrome, stomatitis, and skin rash. Grade 3 lethargy and grade 3 or 4 neutropenia occurred in 40% and 45% of patients, respectively. No GI perforation, grade 3 GI hemorrhage\/hypertension, or pneumonitis occurred. Ten partial responses were observed. Median overall and progression-survival times (all patients) were 12.5 and 9.0 months, respectively. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The maximum-tolerated dose of capecitabine was 1,660 mg\/m<jats:sup>2<\/jats:sup>. The recommended capecitabine dose in this cytotoxic doublet\/biologic doublet regimen is 1,440 mg\/m<jats:sup>2<\/jats:sup>; this regimen is under evaluation in an ongoing phase II study. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2008.21.5384","type":"journal-article","created":{"date-parts":[[2009,10,27]],"date-time":"2009-10-27T01:43:38Z","timestamp":1256607818000},"page":"5499-5505","source":"Crossref","is-referenced-by-count":17,"title":["Dose Finding and Early Efficacy Study of Gemcitabine Plus Capecitabine in Combination With Bevacizumab Plus Erlotinib in Advanced Pancreatic Cancer"],"prefix":"10.1200","volume":"27","author":[{"given":"Naureen","family":"Starling","sequence":"first","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Watkins","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Cunningham","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Thomas","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Webb","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"Brown","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Thomas","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqui","family":"Oates","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Chau","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Radiology, and Computing and Statistics, Royal Marsden Hospital, National Health Service Foundation Trust, Surrey and London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.2.74"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/CA.2007.0010"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604576"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604577"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604436"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-200407000-00061"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000515)88:10<2239::AID-CNCR6>3.0.CO;2-V"},{"key":"B8","first-page":"1309","volume":"3","author":"Itakura J","year":"1997","journal-title":"Clin Cancer Res"},{"key":"B9","first-page":"1936","volume":"6","author":"Bruns CJ","year":"2000","journal-title":"Clin Cancer Res"},{"key":"B10","first-page":"777","volume":"1","author":"Ng SS","year":"2002","journal-title":"Mol Cancer Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000701)89:1<74::AID-CNCR11>3.0.CO;2-K"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1089\/108497801753354267"},{"key":"B13","first-page":"4221","volume":"9","author":"Bockhorn M","year":"2003","journal-title":"Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10681"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0796"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-06-0404"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl962"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205260"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(02)00013-8"},{"key":"B20","first-page":"3739","volume":"6","author":"Ciardiello F","year":"2000","journal-title":"Clin Cancer Res"},{"key":"B21","first-page":"1996","volume":"62","author":"Baker CH","year":"2002","journal-title":"Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.0949"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.477"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.3026"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.9525"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.9661"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6349(05)82014-2"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.20.1637"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.8521"},{"key":"B31","doi-asserted-by":"crossref","first-page":"199s","DOI":"10.1200\/jco.2007.25.18_suppl.4508","volume":"25","author":"Kindler HL","year":"2007","journal-title":"J Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2008.26.15_suppl.4502"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-006-0389-0"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2007.12.011"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm452"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.12.040"},{"key":"B37","doi-asserted-by":"crossref","first-page":"199s","DOI":"10.1200\/JCO.2006.09.6040","volume":"25","author":"Philip PA","year":"2007","journal-title":"J Clin Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.0238"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.5154"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2008.26.15_suppl.lba4011"},{"key":"B41","volume-title":"2008 Gastrointestinal Cancers Symposium","author":"Hecht JR"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.8234"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2008.21.5384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T23:38:55Z","timestamp":1653521935000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2008.21.5384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,20]]},"references-count":42,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2009,11,20]]}},"alternative-id":["10.1200\/JCO.2008.21.5384"],"URL":"https:\/\/doi.org\/10.1200\/jco.2008.21.5384","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,20]]}}}