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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3159 - Determination of DPYD polymorphisms before treatment with chemotherapy with a pyrimidine. Should we continue doing it?

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Cytotoxic Therapy

Tumour Site

Presenters

Claudio Avila Andrade

Citation

Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Authors

C. Avila Andrade1, A.J. Cunquero Tomas2, A.B. Fernandez Diaz1, M. Meri Abad1, L.D. Condori Farfan1, I. Shaheen1, S. Cervantes Garcia3, M.J. Safont Aguilera1, V. Iranzo Gonzalez-Cruz1, V. Sforza4, C. Caballero5, M.C. Godes de Bremond1, M. Gil1, F.D.A. Aparisi Aparisi6, A. Blasco Cordellat7, A. Berrocal Jaime2, I. Ferrer Bolufer3, M. Lobo de Mena7, G. Marcaida Benito3, C. Camps8

Author affiliations

  • 1 Medical Oncology Service, Hospital General Universitario Valencia, 46018 - Valencia/ES
  • 2 Medical Oncology, Hospital General Universitario Valencia, 46018 - Valencia/ES
  • 3 Clinical Analysis, Hospital General Universitario Valencia, 46014 - VALENCIA/ES
  • 4 Department Of Medical Oncology, Università degli Studi della Campania Luigi Vanvitelli, 80131 - Naples/IT
  • 5 Medical Oncology, Hospital General, 460140 - València/ES
  • 6 Oncology, Fundación de Investigación Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 7 Medical Oncology, Hospital General Universitario Valencia, 46018 - Valencia/ES
  • 8 Medical Oncology, Consorcio Hospital General Universitario de Valencia, 46014 - Valencia/ES

Resources

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Abstract 3159

Background

The toxicity produced by chemotherapy worsens in the presence of mutations in certain enzymes of metabolism or degradation. Such is the case of dihydropyrimidine dehydrogenase (DPYD) in the treatment with fluoropyrimidines. Detection prior to the start of treatment could be beneficial to prevent this increase in toxicity.

Methods

A prospective study in which the DPYD polymorphisms are analyzed, after the first visit in Oncology of patients with a diagnosis of colorectal cancer (CRC), gastroesophageal cancer (CGE) or cancer in the head and neck, that can be treated with fluoropyrimidine-based chemotherapy. After DNA extraction from the peripheral blood sample the methodology used was: 1. Directed genotyping of variant * 2A, * 13 and rs67376798 of the DPYD gene, by analysis of allelic discrimination polymorphisms with TAQMAN probes, previous amplification in an ABI Prism 7900 (Applied Biosystems).

Results

We included 374 patients, with an average age of 67a, 62% men, with PS 0 or 1 in 97% of the cases. Localization of the primary tumor was: CRC 85%, GEC 12%, H&N (3%). 97% were adenocarcinomas and 3% squamous carcinoma. The intention of adjuvant treatment in 46%, neoadjuvant 17%, a first line of metastatic disease 33%, the second line of metastatic disease 3%. Schemes used: combinations of 5FU with oxaliplatin (58%), capecitabine in monotherapy or radiotherapy in neoadjuvant (33%). Toxicities G3-4: diarrhea 1.3%, neutropenia 0.8%, rash, 1.3% and mucositis 0.3% Four patients with DPYD deficit (1.1%) were found. two patients with a complete deficit that started capecitabine adjuvant at 50%, increasing to 75% in the 2nd cycle with G1 diarrhea as a relevant toxicity. Another two patients with DPYP heterozygous deficit decided to change treatment scheme to ralitrexed every 3 weeks.

Conclusions

In our study, we observed that the enzymatic deficit in the metabolic pathways related to 5FU are rare, and probably do not influence the initiation of chemotherapy treatment.

These results will not influence the usual clinical practice, but we think are very important to avoid toxicity to the patient if these are present.

Clinical trial identification

Legal entity responsible for the study

Hospital General Valencia Deparment of Medical Oncology.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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