Dataset Information

Usefulness of an S-1 dosage formula: an exploratory analysis of randomized clinical trial (JCOG1001).

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.

SUBMITTER: Kawakami T

PROVIDER: S-EPMC9587934 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Usefulness of an S-1 dosage formula: an exploratory analysis of randomized clinical trial (JCOG1001).

Kawakami Takeshi T Mizusawa Junki J Hasegawa Hiroko H Imazeki Hiroshi H Kano Kazuki K Sato Yuya Y Iwasa Satoru S Takiguchi Shuji S Kurokawa Yukinori Y Doki Yuichiro Y Boku Narikazu N Yoshikawa Takaki T Terashima Masanori M

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20220629 6

<h4>Background</h4>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.<h4>Methods</h4>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 calculate ...[more]

PMID: 35767198

Similar Datasets

Project description:ImportanceThe disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.ObjectiveTo test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.Design, setting, and participantsA double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.InterventionsThe participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.Main outcomesAND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).ResultsThe absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.Conclusions and relevanceAmong infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.

Project description:ImportanceEarly exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas.ObjectiveTo test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children.Design, setting, and participantsAn international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017.InterventionsThe participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age.Main outcomes and measuresPrimary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events).ResultsAmong 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group).Conclusions and relevanceAmong infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.Trial registrationclinicaltrials.gov Identifier: NCT00179777.

Project description:ImportanceClonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of atherosclerotic cardiovascular disease, and mouse experiments suggest that CHIP related to Tet2 loss of function in myeloid cells accelerates atherosclerosis via augmented interleukin (IL) 1β signaling.ObjectiveTo assess whether individuals with CHIP have greater cardiovascular event reduction in response to IL-1β neutralization in the Canankinumab Anti-inflammatory Thrombosis Outcomes Trial (CANTOS).Design, setting, and participantsThis randomized clinical trial took place from April 2011 to June 2017 at more than 1000 clinical sites in 39 countries. Targeted deep sequencing of genes previously associated with CHIP in a subset of trial participants using genomic DNA prepared from baseline peripheral blood samples were analyzed. All participants had prior myocardial infarction and elevated high-sensitivity C-reactive protein level above 0.20 mg/dL. Analysis took place between June 2017 and December 2021.InterventionsCanakinumab, an anti-IL-1β antibody, given at doses of 50, 150, and 300 mg once every 3 months.Main outcomes and measuresMajor adverse cardiovascular events (MACE).ResultsA total of 338 patients (8.6%) were identified in this subset with evidence for clonal hematopoiesis. As expected, the incidence of CHIP increased with age; the mean (SD) age of patients with CHIP was 66.3 (9.2) years and 61.5 (9.6) years in patients without CHIP. Unlike other populations that were not preselected for elevated C-reactive protein, in the CANTOS population variants in TET2 were more common than DNMT3A (119 variants in 103 patients vs 86 variants in 85 patients). Placebo-treated patients with CHIP showed a nonsignificant increase in the rate of MACE compared with patients without CHIP using a Cox proportional hazard model (hazard ratio, 1.32 [95% CI, 0.86-2.04]; P = .21). Exploratory analyses of placebo-treated patients with a somatic variant in either TET2 or DNMT3A (n = 58) showed an equivocal risk for MACE (hazard ratio, 1.65 [95% CI, 0.97-2.80]; P = .06). Patients with CHIP due to somatic variants in TET2 also had reduced risk for MACE while taking canakinumab (hazard ratio, 0.38 [95% CI, 0.15-0.96]) with equivocal difference compared with others (P for interaction = .14).Conclusions and relevanceThese results are consistent with observations of increased risk for cardiovascular events in patients with CHIP and raise the possibility that those with TET2 variants may respond better to canakinumab than those without CHIP. Future studies are required to further substantiate this hypothesis.Trial registrationClinicalTrials.gov Identifier: NCT01327846.

Project description:Enhancing CNS myelin repair (remyelination) is a promising strategy to prevent neurodegeneration and associated progressive disability in multiple sclerosis. Remyelination becomes inefficient with older chronological age, but the relationship between measures of biological age and remyelination has not been previously described in a clinical cohort. Here, we investigated two measures of biological age amongst participants of the Cambridge Centre for Myelin Repair One trial of bexarotene: MRI brain age (BAMRI) and a blood-based biological age (BABlood). In people with radiologically stable multiple sclerosis (n = 44 of 49 total participants), we found that treatment with bexarotene, along with promoting remyelination, was associated with significant decrease in MRI brain age [-1.98 years, 95% confidence interval (CI) [-3.75, -0.21 years] versus placebo over 6 months, P = 0.034]. Whilst BAMRI increased as expected during the trial in the placebo group (+0.92 years, CI [-0.41, 2.26]), the brain MRIs of participants treated with bexarotene appeared on average 11 months younger at the end compared to the start of the trial (-0.93 years, CI [-2.02, 0.17]). The effect of bexarotene on BAMRI was associated with its remyelinating activity in cortical grey matter lesions (β = 0.25% units (pu)/year, CI [0.03, 0.46], P = 0.023) and brainstem lesions (β = 0.24 pu/year, CI [0.09, 0.39], P = 0.003). We also observed some regional trends that the remyelinating response to bexarotene was linked with measures of biological age at baseline. For example, after adjustment for chronological age, remyelination of brainstem lesions assessed by magnetization transfer ratio was reduced by 0.06 pu for each year increase in BAMRI (CI [0.00, 0.13], P = 0.058) and 0.02 pu for each year increase in BABlood (CI [-0.01, 0.05], P = 0.17). This is, to the best of our knowledge, the first demonstration that MRI brain age can be therapeutically modulated by a drug in people with a neurological disorder. Overall, these findings highlight that beyond chronological age, biological age may also influence the potential for repair and should be considered when developing treatments for multiple sclerosis.

Dataset Information

Usefulness of an S-1 dosage formula: an exploratory analysis of randomized clinical trial (JCOG1001).

Background

Methods

Results

Conclusions

Publications

Usefulness of an S-1 dosage formula: an exploratory analysis of randomized clinical trial (JCOG1001).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets