(064) Capecitabine-Induced Adverse Reactions in Patients with Biliary Tract Cancer: Evidence from Spontaneous Reporting Data Analysis and Systematic Review & Meta-Analysis

Publication Number: 1060

Background: Spontaneous Reporting Systems (SRSs) such as the UK Yellow card Scheme for reporting suspected adverse drug reactions (ADRs) operate in developed countries and many developing countries. The main function of SRS is the early detection of signals of new, rare, or serious ADRs. Patients with biliary tract cancer (BTC) experience a dismal outcome despite advancements in multidisciplinary management.

Objectives: To assess the pattern of capecitabine-induced adverse reactions in patients with biliary tract cancer (BTC).

Methods: Considered the ADRs of capecitabine among patients with BTC reported from the ADR Monitoring Centre between July and December 2022. Assessment of causality and severity of ADRs was performed by using WHO Scale and Common Terminology Criteria for Adverse Events (CTCAE), respectively. A thorough literature search was performed in PubMed, Cochrane CENTRAL, and Google Scholar from the inception to 1st August 2022 to identify the randomized controlled trials published on adverse events among BTC patients. The Fixed or Random-effects model was used based on the heterogeneity identified by using the I² statistic and Cochran's Q test.

Results: Out of 43 ADRs reported for capecitabine, seven (33.3%) were on patients with BTC. All seven ADRs were palmar-plantar erythrodysesthesia with probable causality. According to CTCAE number of ADRs reported with Severe [2 ADRs (Grade 3)], Moderate [4 ADRs (Grade 2)], and Mild [1 ADR (Grade 1)]. Out of 350 non-duplicate RCTs identified through database searching, a total of 21 studies with 1685 patients were included in the systematic review. Palmar-plantar erythrodysesthesia (OR 3.18, 95% CI: 0.69-14.66, p=0.14), neuropathy (OR 1.47, 95% CI: 0.84-2.58, p=0.18) was found to be and higher in the capecitabine group compared to the control group, and neutropenia (OR 0.67, 95% CI: 0.41-1.09, p=0.10), thrombocytopenia (OR 0.66, 95% CI: 0.20-2.17, p=0.49) was lower in the capecitabine group to the control group. However, all the results were found to be non-significant.

Conclusions: The study reveals that palmar-plantar erythrodysesthesia and neuropathy are the main adverse events associated with capecitabine in BTC. Underreporting and lower population size trials can be the reason for non-significant results from the systematic review.