Takeshi Kawakami1, Junki Mizusawa2, Hiroko Hasegawa3, Hiroshi Imazeki4, Kazuki Kano5, Yuya Sato6, Satoru Iwasa7, Shuji Takiguchi8, Yukinori Kurokawa9, Yuichiro Doki9, Narikazu Boku10, Takaki Yoshikawa11, Masanori Terashima12. 1. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. t.kawakami@scchr.jp. 2. Japan Clinical Oncology Group Data Center, National Cancer Center Hospital, Tokyo, Japan. 3. Department of Gastroenterology and Hepatology, National Hospital Organization, Osaka National Hospital, Osaka, Japan. 4. Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan. 5. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. 6. Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan. 7. Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 8. Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, Nagoya, Japan. 9. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. 10. Department of Oncology and General Medicine, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo, Japan. 11. Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan. 12. Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
Abstract
BACKGROUND: The blood concentration of S-1 and adverse events are affected by renal function. Herein, an S-1 dosage formula was developed based on renal function, indicating the dose for a target blood concentration. This study aimed to explore the usefulness of the formula in adjuvant chemotherapy for gastric cancer. METHODS: In this ad hoc analysis of the JCOG1001 trial, which evaluated the role of bursectomy for resectable gastric cancer, the recommended dose of S-1 was calculated using the following formula: 1447.8 × (14.5 + 0.301 × CLcr + 8.23 × SEX [male = 1, female = 0]) × body surface area (BSA) (mg/day). Patients were divided into three groups by comparing the initial S-1 dose determined using BSA with the dose recommended by the formula: underdose (UD), equal dose (ED), and overdose (OD). RESULTS: Among 686 eligible patients, 58, 304, and 324 patients were classified into the UD, ED, and OD groups. The patients' characteristics in the UD/ED/OD groups were median age (53.5/64.0/67.5 years), male sex (98.3%/75.3%/58.0%), and median BMI (24.8/22.8/22.3), respectively. The planned 1-year adjuvant S-1 therapy was completed in 74.1%/73.7%/68.5%, dose reduction was required in 8.6%/21.1%/30.6%, and treatment schedule was altered in 8.6%/17.1/19.8% in the UD/ED/OD groups, resulting in the 5-year overall survival rates of 77.3%/74.3%/77.0%, respectively. The incidences of grade > 3 anemia, thrombocytopenia, diarrhea, stomatitis, and anorexia were significantly higher in the OD group than in the ED and UD groups. CONCLUSIONS: Dose optimization using an S-1 dosage formula can potentially reduce grade ≥ 3 adverse events for overdosed patients.
BACKGROUND: The blood concentration of S-1 and adverse events are affected by renal function. Herein, an S-1 dosage formula was developed based on renal function, indicating the dose for a target blood concentration. This study aimed to explore the usefulness of the formula in adjuvant chemotherapy for gastric cancer. METHODS: In this ad hoc analysis of the JCOG1001 trial, which evaluated the role of bursectomy for resectable gastric cancer, the recommended dose of S-1 was calculated using the following formula: 1447.8 × (14.5 + 0.301 × CLcr + 8.23 × SEX [male = 1, female = 0]) × body surface area (BSA) (mg/day). Patients were divided into three groups by comparing the initial S-1 dose determined using BSA with the dose recommended by the formula: underdose (UD), equal dose (ED), and overdose (OD). RESULTS: Among 686 eligible patients, 58, 304, and 324 patients were classified into the UD, ED, and OD groups. The patients' characteristics in the UD/ED/OD groups were median age (53.5/64.0/67.5 years), male sex (98.3%/75.3%/58.0%), and median BMI (24.8/22.8/22.3), respectively. The planned 1-year adjuvant S-1 therapy was completed in 74.1%/73.7%/68.5%, dose reduction was required in 8.6%/21.1%/30.6%, and treatment schedule was altered in 8.6%/17.1/19.8% in the UD/ED/OD groups, resulting in the 5-year overall survival rates of 77.3%/74.3%/77.0%, respectively. The incidences of grade > 3 anemia, thrombocytopenia, diarrhea, stomatitis, and anorexia were significantly higher in the OD group than in the ED and UD groups. CONCLUSIONS: Dose optimization using an S-1 dosage formula can potentially reduce grade ≥ 3 adverse events for overdosed patients.
Authors: T Shirasaka; K Nakano; T Takechi; H Satake; J Uchida; A Fujioka; H Saito; H Okabe; K Oyama; S Takeda; N Unemi; M Fukushima Journal: Cancer Res Date: 1996-06-01 Impact factor: 12.701
Authors: T Shirasaka; Y Shimamato; H Ohshimo; M Yamaguchi; T Kato; K Yonekura; M Fukushima Journal: Anticancer Drugs Date: 1996-07 Impact factor: 2.248