272P - Correlation of dihydropyrimidine dehydrogenase gene mutation with toxicity among gastrointestinal cancers (GI) taking 5-fluorouracil-based chemotherapy: Experience from a tertiary cancer center in eastern part of India

Background

5-fluorouracil (5-FU) is a major component of chemotherapy regimens in gastrointestinal (GI) cancers. Mutation in Dihydropyrimidine Dehydrogenase (DPD) gene can cause severe 5-FU related toxicity. Identifying the mutation helps in predicting the toxicity and adjusting dose of 5-FU. Our study assesses and analyze the utility of DPD testing at our center.

Methods

Data of GI cancer patients who has been tested for DPD enzyme while planning chemotherapy (for both adjuvant and palliative settings) was extracted from our center’s electronic records from the 1st June 2016 to 31st December 2021 and evaluated. We collected demographics of the patients, genotypes of DPD gene, disease status, chemotherapy type and the associated toxicities.

Results

Total 211 patients were tested for the DPD gene with median age of 66 years (Female=78). 120 patients were found to have mutation. There were 6 different DPD genotypes in our dataset. Among mutated ones, 36% were female. Seven patients were homozygous for some DPD gene variants, most common was *9A (c.85 T>C; p.C29R) genotype. While 2 out of 7 had severe diarrhea (Grade 3/4, CTCAE V.5) during chemotherapy, no patient died of toxicity. Among mutated vs non-mutated patients, grade 3/4 diarrhoea was 25% vs 38% (Chi Sq (1, N = 65) = 4.39, p = .035), anemia was 10% vs 9% (Chi Sq (1, N=21) = 0.0007, p= .978), neutropenia was 9% vs 4% (Chi Sq (1, N=15) =1.78, p= .181), thrombocytopenia was 5% vs 3% (Chi Sq (1, N=9) = 0.36, p= .544), mucositis was 6% vs 1% (Chi Sq (1, N=9) = 3.92, p= .047). Most patients with Grade 3/4 toxicity were on combination chemotherapy. We found 9 different DPD genotypes in our population. Among them, *9A (c.85 T>C; p.C29R) caused most severe GI toxicity, *2A (c.14+1 G>A) genotype resulted in severe hematological and GI toxicity. We lost one patient to toxicity having heterozygous *6 (2194 G/A; p.V732I) mutation.

Conclusions

DPD gene testing can help in predicting the toxicity to 5-FU based chemotherapy. We found that diarrhea and mucositis were related to the DPD gene mutation more than anemia, neutropenia and thrombocytopenia. Genotype analysis should be an important part of the treatment plan for GI cancers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Tanuj Chawla.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.