Usefulness of an S-1 dosage formula: an exploratory analysis of randomized clinical trial (JCOG1001).
Adjuvant chemotherapy
Dosage formula
Gastric cancer
Renal function
S-1
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
16
04
2022
accepted:
04
06
2022
pubmed:
30
6
2022
medline:
26
10
2022
entrez:
29
6
2022
Statut:
ppublish
Résumé
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. 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). 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. Dose optimization using an S-1 dosage formula can potentially reduce grade ≥ 3 adverse events for overdosed patients.
Sections du résumé
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.
Identifiants
pubmed: 35767198
doi: 10.1007/s10120-022-01315-8
pii: 10.1007/s10120-022-01315-8
pmc: PMC9587934
doi:
Types de publication
Randomized Controlled Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1073-1081Informations de copyright
© 2022. The Author(s).
Références
Cancer Res. 1996 Jun 1;56(11):2602-6
pubmed: 8653704
Gastric Cancer. 2022 Jul;25(4):770-782
pubmed: 35357635
Gastric Cancer. 2018 May;21(3):446-452
pubmed: 28965205
Cancer Res. 1993 Sep 1;53(17):4004-9
pubmed: 7689420
Anticancer Drugs. 1996 Jul;7(5):548-57
pubmed: 8862723
Gastric Cancer. 2016 Jul;19(3):876-86
pubmed: 26304171
Ann Surg Oncol. 2017 Sep;24(9):2639-2645
pubmed: 28608116
Cancer Sci. 2013 Jan;104(1):116-23
pubmed: 23066919
Cancer Sci. 2021 Feb;112(2):751-759
pubmed: 33277781
Lancet Oncol. 2008 Mar;9(3):215-21
pubmed: 18282805
J Clin Oncol. 2019 May 20;37(15):1296-1304
pubmed: 30925125
Lancet Gastroenterol Hepatol. 2018 Jul;3(7):460-468
pubmed: 29709558
Oncol Lett. 2012 Nov;4(5):1135-1139
pubmed: 23162667
Gastric Cancer. 2021 Nov;24(6):1184-1193
pubmed: 34365541
N Engl J Med. 2007 Nov 1;357(18):1810-20
pubmed: 17978289