Role of oral metronomic chemotherapy with best supportive care vs. best supportive care among treatment naive advanced and/or metastatic Gastrointestinal cancers patients with KPS 30-60

The proposed study aims to evaluate the effectiveness of adding low-dose oral capecitabine to best supportive care (BSC) in improving clinical outcomes for patients with advanced or metastatic gastrointestinal cancers. This population, often frail and with limited functional capacity (Karnofsky Performance Status 30-60), presents unique challenges in terms of therapeutic tolerance and quality of life management.

The primary objective is to assess whether oral metronomic capecitabine in combination with BSC improves patient performance status from a KPS of 30-60 to above 60 over 12 weeks, indicating better functionality and potentially a greater capacity for daily activities and tolerability to standard of care chemotherapy doses. Primary objective will be to see Conversion rate (%) of patients from KPS 30 - 60 to above 60 within or at end of 12 weeks. Secondary objectives include evaluating symptom control, pain relief, quality of life, and any adverse effects of the therapy, and tertiary outcomes are progression-free survival and overall survival in both study groups. The study is designed as an open-label, randomized controlled trial with 50  participants divided equally into two groups: one receiving oral capecitabine (500 mg twice daily) alongside BSC, and the other receiving BSC alone. The randomization process will ensure balanced allocation, and data collection will be structured using a standard case record form.

Inclusion criteria encompass adults with advanced or metastatic gastrointestinal cancer who are chemotherapy-naïve and have a KPS between 30-60, indicating moderate to severe clinical performance impairment. Exclusion criteria include those with KPS below 30 and above 60, abnormal liver function (total bilirubin > 3 times upper normal limit (UNL), AST and ALT >3 times in the absence of liver metastasis or > 5 times in the presence of liver metastasis), abnormal Kidney function with creatinine clearance of less than 30 ml/min/ 1.73 m2 BSA with cockrauft gault formula., New York Heart Association grade III or IV congestive heart failure, or history of unstable angina/ myocardial infarction within six months prior to study entry, Pregnant and lactating females, Children below 18 years of age, Brain metastasis , hemodynamic instability, active infection or sepsis, Any acquired immunodeficiency state.

Descriptive statistics will be presented as mean with standard deviation or median with interquartile range in case of continuous variables and percentage will be used for categorical variables. Student t-test will be used to calculate the difference of mean for normality distributed variables and Kruskal-Wallis test will be applied for skewed data. The chi-square test was used for the calculation of differences in categorical variables. The median survival time will be calculated using the Kaplan-Meier curves and a comparison of this estimate between groups is made using a log-rank test. P value <0.05 will be considered as statistically significant.

This study intends to provide insights into metronomic chemotherapy’s potential benefits in supportive oncology, targeting a demographic with limited options and significant clinical need. The Institutional ethics committee has approved to this trial.