Phase I Study of Alternate-Day Administration of S-1, Oral Leucovorin, and Bevacizumab for Refractory Metastatic Colorectal Cancer.

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.

• Authors: Toshiki Masuishi, Hiroya Taniguchi, Azusa Komori, Seiichiro Mitani, Yukiya Narita, Shigenori Kadowaki, Takashi Ura, Masashi Ando, Kei Muro
• Journal: The oncologist (Oncologist) Vol. 25 Issue 11 Pg. e1614-e1620 (11 2020) ISSN: 1549-490X [Electronic] England
• PMID: 32490554 (Publication Type: Clinical Trial, Phase I, Journal Article)
• Copyright: © AlphaMed Press; the data published online to support this summary are the property of the authors.

Chemical References

• Drug Combinations
• S 1 (combination)
• Tegafur
• Bevacizumab
• Oxonic Acid
• Leucovorin
• Fluorouracil

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Bevacizumab (therapeutic use)
• Colorectal Neoplasms (drug therapy)
• Drug Combinations
• Female
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Male
• Middle Aged
• Oxonic Acid (therapeutic use)
• Tegafur (therapeutic use)
• Treatment Outcome