Home
Home
  • Home
  • About Us About Us
    • Overview
    • Who we are
    • Why we provide advice
    • What are health technologies
    • Meetings
    • News
    • Who we work with
    • Contact Us
  • What We Do What We Do
    • Overview
    • Our Strategy
    • Work programme
    • Range of advice products
    • Quarterly Bulletin of advice
    • Early HTA Advice Service
  • Our Advice
  • Request Advice Request Advice
    • Overview
    • Form for requesting advice
  • Get Involved Get Involved
    • Overview
    • Contribute to advice
    • NHS boards
    • Patient and Public Involvement
    • Industry Involvement
    • Observe a council meeting
    • DOI Form

SHTG Assessment

  • Home
  • Our Advice
  • Pre-treatment DPYD genetic testing for patients who are prescribed chemotherapy involving fluoropyrimidines

Title

Output Type

Speciality

Published

Title

Pre-treatment DPYD genetic testing for patients who are prescribed chemotherapy involving fluoropyrimidines

Output Type

SHTG Assessment

Speciality

Cancer

Published

28 October 2020

Key Findings

Two systematic reviews and an individual patient data meta-analysis reported clinically significant increases in risk of severe (grade ≥3) fluoropyrimidine (FP)-related toxicity in patients with DPYD gene variants c.1905+1G>A, c.2846A>T, c.1679T>G, or c.1236G>A/Hap B3. No clinically significant increase in risk of severe toxicity was found in patients with DPYD variant c.1601G>A.

Four cohort studies – two prospective and two retrospective – explored the feasibility and effects of DPYD genetic testing in routine clinical practice.

  • All four studies reported successful implementation of DPYD genetic testing, with subsequent individualisation of FP dose for patients with clinically relevant DPYD variants.
  • The two comparative prospective studies demonstrated a significant reduction in risk of severe (grade ≥3) treatment-related toxicity in patients with DPYD variants treated with reduced doses of FP compared with historical cohorts receiving a full dose.
  • In one of the prospective studies the frequency of treatment-related severe (grade ≥3) toxicity in patients with DPYD variant c.1905+1G>A, receiving reduced doses of FP, was similar to that of wild-type variant patients receiving a full FP dose. In the second prospective study, despite FP dose reduction, the risk of severe toxicity remained elevated in patients with DPYD variants c.1236G>A or c.2846A>T compared with wild-type variant patients

Four published costing studies found that a pre-treatment testing strategy for DPYD gene variants is likely to be cost saving compared to reactive testing.

SHTG conducted an economic analysis using Scottish incidence and cost data. The model compared the costs and adverse events associated with a strategy of prospective DPYD genetic testing for patients eligible for FP based chemotherapy versus a strategy of no testing.

  • Prospective testing was the dominant strategy. This meant it was less costly and led to fewer adverse events and associated hospital admissions compared to a no-testing strategy.
  • The model predicted that up to 24 serious adverse events could be averted for every 1,000 patients tested.
  • The incremental costs of DPYD testing are expected to be offset by lower expenditure on acute and in-patient care for patients experiencing adverse events.

What were we asked to look at?

We were asked to determine the economic case for routine pretreatment DPYD genetic testing for patients who are prescribed fluoropyrimidine-based chemotherapy.

Why is this important?

Fluoropyrimidines are chemotherapy drugs frequently used in the treatment of several types of cancer. Approximately 10% to 30% of patients treated with fluoropyrimidines experience severe (grade≥3) treatment-related toxicities. Changes to the DPYD gene can lead to dihydropyrimidine dehydrogenase (DPD) enzyme deficiency, which can lead to the accumulation of cytotoxic chemotherapy compounds in the body and cause severe side effects. Pre-treatment genetic testing could facilitate the delivery of tailored chemotherapy dosing schedules and reduce severe fluoropyrimidine-related toxicity in patients.

Referred by

NHS National Services Scotland

 

Download icon
Download Advice
pdf (430 KB)

Connect with Us

Please let us know if you'd like to receive regular updates on our work.


Last Updated: 31 January 2022

Scottish Health Technologies Group

© 2021, All rights reserved

  • Accessibility
  • Respecting your privacy
  • Cookies
  • Healthcare Improvement Scotland Website
  • Find us on Twitter
  • Freedom of Information

Tell us what you think


We'd love to hear your views

Was our advice useful?  Did you find what you were looking for on our website?