Sergio Cifuentes-Canaval, Medical Oncologist at Las Américas Auna Clinic, shared a post on LinkedIn:
“DPYD testing before fluoropyrimidines: a major unmet need in LATAM
Fluoropyrimidines (5-FU and capecitabine) remain foundational treatments across gastrointestinal and breast cancers in Latin America. However, pretreatment DPYD testing is still not routinely implemented, despite strong evidence linking DPD deficiency to severe and preventable toxicity.
DPYD genotype and DPD activity (CPIC classification):
Poor metabolizers (Activity Score 0–0.5)
→ Complete DPD deficiency
Fluoropyrimidines should be avoided
Intermediate metabolizers (Activity Score 1.0–1.5)
→ Partial DPD deficiency
Initial dose reduction required
Normal metabolizers (Activity Score 2.0)
→ Standard dosing
CPIC guideline recommendations for fluoropyrimidine dosing:
- AS 0–0.5: Do not use 5-FU or capecitabine
- AS 1.0: Start at ~50% of standard dose, with careful escalation if tolerated
- AS 1.5: 25–50% dose reduction (50% commonly recommended; 25% may be considered for HapB3 variants with close monitoring)
- AS 2.0: Standard dosing
Key considerations:
- Approximately 6% of patients have partial DPD deficiency
- The majority of life-threatening toxicities occur in this subgroup
- DPYD testing is primarily a patient safety intervention, not a strategy for efficacy optimization
Why this matters in LATAM:
In many LMIC settings, fluoropyrimidines are widely used while access to DPYD testing remains limited. This gap contributes to avoidable hospitalizations, treatment interruptions, and treatment-related mortality—placing additional strain on already resource-constrained health systems.
Take-home message:
Implementing pretreatment DPYD testing before 5-FU or capecitabine represents a high-value, evidence-based strategy to improve patient safety and sustainability of cancer care in Latin America.”
Title: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update
Authors: Ursula Amstutz, Linda Henricks, Steven Offer, Julia Barbarino, Jan Schellens, Jesse Swen, Teri Klein, Howard McLeod, Kelly Caudle, Robert Diasio, Matthias Schwab
Read the Full Article in ASCPT.
Title: Ending the Controversy Around Pretreatment Dihydropyrimidine Dehydrogenase (DPD/DPYD) Testing Heightens the Controversy Over Appropriate Fluoropyrimidine Dosing
Authors: Daniel L. Hertz, Alan P. Venook
Read the Full Article in Journal of Clinical Oncology .
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