Toshiki Masuishi 1 , Hiroya Taniguchi 1,2 , Azusa Komori 1 , Seiichiro Mitani 1 , Yukiya Narita 1 , Shigenori Kadowaki 1 , Takashi Ura 1 , Masashi Ando 1 , Kei Muro 1 Show Affiliations »
Abstract
LESSONS LEARNED: 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. BACKGROUND: 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. METHODS: 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 weeks. Enrollment continued at the recommended dose level in the expansion cohort. RESULTS: 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 1-3 and ≥4 prior treatment lines, respectively. Dose-limiting toxicity (DLT) was not observed, and level 2 was confirmed as the recommended dose. Common grade 3-4 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. CONCLUSION: 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 weeks. Compared with the daily administration, alternate-day administration of S-1 plus leucovorin may reduce mucositis with promising antitumor activity in refractory mCRC. © AlphaMed Press; the data published online to support this summary are the property of the authors.
LESSONS LEARNED: 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 . BACKGROUND: 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 . METHODS: 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 weeks. Enrollment continued at the recommended dose level in the expansion cohort. RESULTS: 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 1-3 and ≥4 prior treatment lines, respectively. Dose-limiting toxicity (DLT) was not observed, and level 2 was confirmed as the recommended dose. Common grade 3-4 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. CONCLUSION: 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 weeks. Compared with the daily administration, alternate-day administration of S-1 plus leucovorin may reduce mucositis with promising antitumor activity in refractory mCRC. © AlphaMed Press; the data published online to support this summary are the property of the authors.
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Year: 2020
PMID： 32490554 PMCID： PMC7648368 DOI： 10.1634/theoncologist.2020-0463
Source DB: PubMed Journal: Oncologist ISSN： 1083-7159