{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T18:42:01Z","timestamp":1648579321089},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Trial Information<\/jats:title>\n                  <jats:p>Click here to access other published clinical trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>The recommended S-1 dose was 40 mg\/m2, twice daily on Monday, Wednesday, Friday, and Sunday, with oral leucovorin and bevacizumab. Compared with daily administration, the alternate-day administration of S-1 with oral leucovorin may reduce mucositis with promising antitumor activity in refractory metastatic colorectal cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Daily S-1 plus oral leucovorin administration in a 1-week-on\/1-week-off schedule has promising efficacy in gastrointestinal cancer but is associated with high risk of mucositis and diarrhea.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This phase Ib, 3+3 dose-escalation trial included patients with chemorefractory metastatic colorectal cancer (mCRC) receiving S-1 (40 mg\/m2) and leucovorin (25 mg) orally twice daily (level 1, even-numbered days; level 2, Monday, Wednesday, Friday, and Sunday) and intravenous bevacizumab (5 mg\/kg) every 2\u2009weeks. Enrollment continued at the recommended dose level in the expansion cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We enrolled 21 patients (3 and 18 patients in levels 1 and 2, respectively). Briefly, 12 and 9 patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 and 1, respectively, and 8 and 13 patients had 1\u20133 and \u22654 prior treatment lines, respectively. Dose-limiting toxicity (DLT) was not observed, and level 2 was confirmed as the recommended dose. Common grade 3\u20134 adverse events at level 2 were anemia (22%), anorexia (6%), and diarrhea (6%). In the entire cohort, response rate, disease control rate, and median progression-free survival were 10%, 71%, and 4.2 months, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The recommended S-1 dose was 40 mg\/m2, twice daily on Monday, Wednesday, Friday, and Sunday, with 25 mg oral leucovorin twice daily and 5 mg\/kg bevacizumab every 2\u2009weeks. Compared with the daily administration, alternate-day administration of S-1 plus leucovorin may reduce mucositis with promising antitumor activity in refractory mCRC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2020-0463","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T10:15:20Z","timestamp":1591179320000},"page":"e1614-e1620","source":"Crossref","is-referenced-by-count":0,"title":["Phase I Study of Alternate-Day Administration of S-1, Oral Leucovorin, and Bevacizumab for Refractory Metastatic Colorectal Cancer"],"prefix":"10.1093","volume":"25","author":[{"given":"Toshiki","family":"Masuishi","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroya","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, 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