- Email: [email protected]
Dpyd Genotyping As a Predictive Biomarker of Toxicity in Breast Cancer
Annals of Oncology 25 (Supplement 4): iv116–iv136, 2014 doi:10.1093/annonc/mdu329.57
breast cancer, metastatic 408P
DPYD GENOTYPING AS A PREDICTIVE BIOMARKER OF TOXICITY IN BREAST CANCER
abstracts
Aim: Capecitabine is an orally bioavailable pro-drug of 5-fluorouracil (5FU) used for the treatment of metastatic breast cancer (m-BC). Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5FU and eliminates more than 80% of the administered drug. DPD deficiency is an autosomal recessive disorder associated with significant morbidity and mortality in those with complete or relative deficiency (incidence 0.1% and 5% respectively). Our aim was to determine whether DPD testing could be used as a biomarker of toxicity. Methods: Consecutive patients with m-BC who received capecitabine in our institution from December 2012 to December 2013 were identified. Records were reviewed for 1) admission to hospital, 2) cost-efficiency analysis of DPD testing and 3) capecitabineassociated toxicities. For all our outcomes we used descriptive analysis. DPD testing was done according to our institution’s guidelines with the genotyping of four DPYD sequence variants associated with reduced DPD activity. Patients were divided into two groups (A) those who had DPD deficiency and (B) those who did not or who were not tested. Results: Forty-eight patients received capecitabine, F:M (46:2), mean age 57 years (range, 35-83). Two patients in each group were admitted to hospital: Group A for 17 and 52 days, Group B for 2 and 5 days. Cost of hospitalization for patients in group A was 9 times that of group B. The cost of DPD testing is < £50. Incidence of grade 3 plantar-palmar erythema, mucositis, fatigue, diarrhoea and thrombocytopenia was 100%, 100%, 100%, 100% and 50% for patients in group A and 20%, 4%, 2%, 4%, 0% for patients in group B. Conclusions: This analysis suggests that testing for DPD deficiency could be a potentially useful predictive biomarker of toxicity in patients with m-BC planned to receive capecitabine. Those with a genetic variant could either avoid capecitabine or start at a reduced dose. We plan to prospectively validate these results by implementing DPD testing for a period of one year in this patient group. Disclosure: All authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv134/2241155 by guest on 25 October 2019
D. Papadatos-Pastos1, K. De Souza1, L. Karapanagiotou1, I. Sandri1, T. Marinaki2, J.L. Mansi3 1 Medical Oncology - Guy’s Hospital, 4th Floor, Bermondsey Wing, Guy’s and St. Thomas’ Hospital NHS Trust, London, UK 2 Biomedical Sciences, Guy’s and St. Thomas’ Hospital NHS Trust, London, UK 3 Medical Oncology Offices, 4th Floor Bermondsey Wing, Guys Hospital, Guys and St Thomas’s NHS Trust, London, UK
breast cancer, metastatic 408P
DPYD GENOTYPING AS A PREDICTIVE BIOMARKER OF TOXICITY IN BREAST CANCER
abstracts
Aim: Capecitabine is an orally bioavailable pro-drug of 5-fluorouracil (5FU) used for the treatment of metastatic breast cancer (m-BC). Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5FU and eliminates more than 80% of the administered drug. DPD deficiency is an autosomal recessive disorder associated with significant morbidity and mortality in those with complete or relative deficiency (incidence 0.1% and 5% respectively). Our aim was to determine whether DPD testing could be used as a biomarker of toxicity. Methods: Consecutive patients with m-BC who received capecitabine in our institution from December 2012 to December 2013 were identified. Records were reviewed for 1) admission to hospital, 2) cost-efficiency analysis of DPD testing and 3) capecitabineassociated toxicities. For all our outcomes we used descriptive analysis. DPD testing was done according to our institution’s guidelines with the genotyping of four DPYD sequence variants associated with reduced DPD activity. Patients were divided into two groups (A) those who had DPD deficiency and (B) those who did not or who were not tested. Results: Forty-eight patients received capecitabine, F:M (46:2), mean age 57 years (range, 35-83). Two patients in each group were admitted to hospital: Group A for 17 and 52 days, Group B for 2 and 5 days. Cost of hospitalization for patients in group A was 9 times that of group B. The cost of DPD testing is < £50. Incidence of grade 3 plantar-palmar erythema, mucositis, fatigue, diarrhoea and thrombocytopenia was 100%, 100%, 100%, 100% and 50% for patients in group A and 20%, 4%, 2%, 4%, 0% for patients in group B. Conclusions: This analysis suggests that testing for DPD deficiency could be a potentially useful predictive biomarker of toxicity in patients with m-BC planned to receive capecitabine. Those with a genetic variant could either avoid capecitabine or start at a reduced dose. We plan to prospectively validate these results by implementing DPD testing for a period of one year in this patient group. Disclosure: All authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv134/2241155 by guest on 25 October 2019
D. Papadatos-Pastos1, K. De Souza1, L. Karapanagiotou1, I. Sandri1, T. Marinaki2, J.L. Mansi3 1 Medical Oncology - Guy’s Hospital, 4th Floor, Bermondsey Wing, Guy’s and St. Thomas’ Hospital NHS Trust, London, UK 2 Biomedical Sciences, Guy’s and St. Thomas’ Hospital NHS Trust, London, UK 3 Medical Oncology Offices, 4th Floor Bermondsey Wing, Guys Hospital, Guys and St Thomas’s NHS Trust, London, UK