ESTRO 2024 - Abstract Book

S1525

Clinical - Lower GI

ESTRO 2024

Purpose/Objective:

Patients with a rectal cancer diagnosis receiving fluoropyrimidine (Capecitabine) based chemoradiotherapy undergo pre-treatment screening for four DPYD gene variants known to cause DPD deficiency, which increases the risk of severe treatment related toxicity (With, M.D. et al, 2023). If identified as DPD deficient, patients receive a reduced starting dose of Capecitabine as per international guidelines (Amstutz, U. et al, 2017) (EMA, 2020). Guidelines recommend an initial two-week 50% dose reduction (DR) of Capecitabine to reduce the risk of severe (grade 3 or above) treatment related toxicity (UK Chemotherapy Board, 2020). Capecitabine dose is titrated thereafter depending on severity of toxicity and clinical judgement, to a maximum of 75% total dose (NHS England, 2020). As Capecitabine is prescribed as a radiosensitiser, patients receiving concurrent chemoradiotherapy receive a Capecitabine DR as standard compared to patients receiving monotherapy. Published recommendations (EMA, 2020) are based on a monotherapy treatment approach and have not investigated dose related toxicity or treatment response in the concurrent chemoradiotherapy rectal cancer population. This study aimed to determine the impact of a Capecitabine dose reduction in DPD deficient patients compared to non-DPD deficient patients with a rectal cancer diagnosis receiving chemoradiotherapy. Primary objectives included comparison of;

1. Tumour regression grade (TRG)

2. Toxicity

3. Compliance to published recommendations

Material/Methods:

Patients from a large regional centre in the UK were identified using the colorectal cancer database. Data from on-treatment review clinics and post treatment imaging were retrieved for matched groups of thirty-two patients (N=16 DPD deficient: N=16 non-DPD deficient) who received concurrent chemoradiotherapy (Capecitabine). Data collection included Common Terminology Criteria for Adverse Events (CTCAE) graded bowel toxicity, TRG and adherence to chemotherapy dose escalation recommendations. After normality testing with Shapiro-Wilk, a comparison of response to treatment using tumour regression grade (TRG) was performed using a 1-tailed Mann-Whitney U Test with a significance level of 0.05. CTCAE graded bowel toxicity was compared between cohorts. Dose escalation practices were recorded and compared to recommendations.

Results:

Data from 32 patients was passed for analysis and demographics for the two groups were matched well.

In the DPD deficient cohort, 100% of patients received the recommended starting DR of 50%. Overall, 69% of patients received a dose escalation after week two and 31% of patients did not due to clinician’s decision. The majority of patients (75%) receiving a dose increase experienced an increase to 75% of total dose after week two.