1. Division of Pharmacy, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan;
2. Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, Bunkyou, Matsuyama, Ehime 790-8578, Japan;
3. Division of Gastrointestinal Surgery and Surgical Oncology, Department of Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
* Hitoshi Kawazoe and Maya Shimasaki equally contributed to this work.
Purpose: The aim of this study was to clarify the risk factors for discontinuing tegafur/gimeracil/oteracil potassium (S-1) adjuvant chemotherapy following gastrectomy in patients with gastric cancer.
Methods: We retrospectively investigated patients with curatively-resected gastric cancer who received S-1 adjuvant chemotherapy. S-1 was administered orally at 80-120 mg/day, depending on body surface area, on days 1-28 every 6 weeks for 1 year. The dose and treatment schedule were modified at the clinicians' discretion, according to toxicity.
Results: Seventy-one patients were included in the study, 26 of whom discontinued S-1 therapy. The relapse-free survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 88.1% and 55.8%, respectively. The overall survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 89.4% and 59.8%, respectively. The hazard ratios for relapse and death were significantly lower in the S-1-completed group compared with those in the S-1-discontinuation group (0.18; p<0.001 and 0.19; p=0.002, respectively). Multivariate logistic regression analysis revealed that S-1 discontinuation was significantly associated with an initial overdose of S-1, having stage I cancer, creatinine clearance <66 mL/min, and a side effect of nausea.
Conclusions: These results suggest that assessing renal function to avoid initial overdose of S-1, together with the early management of side effects, may support the continuation of S-1 adjuvant chemotherapy in patients with gastric cancer.
Keywords: Adjuvant chemotherapy, Tegafur/gimeracil/oteracil potassium (S-1), Gastric cancer, Discontinuation, Risk factor.