DPD-based adaptive dosing of 5-FU in patients with head and neck cancer: impact on treatment efficacy and toxicity

@article{Yang2010DPDbasedAD,
  title={DPD-based adaptive dosing of 5-FU in patients with head and neck cancer: impact on treatment efficacy and toxicity},
  author={Chen Guang Yang and Joseph Ciccolini and Aurore Blesius and Laetitia Dahan and Danielle Bagarry-Liegey and Caroline Brunet and Arthur Varoquaux and Nicolas Frances and Hafedh Marouani and Antoine Giovanni and Rose-Marie Ferri-Dessens and Mohamed Chefrour and Roger Favre and Florence Duffaud and Jean François Seitz and Michel Zanaret and Bruno Lacarelle and C{\'e}dric Mercier},
  journal={Cancer Chemotherapy and Pharmacology},
  year={2010},
  volume={67},
  pages={49-56}
}
BackgroundFluoropyrimidine drugs are widely used in head and neck cancer (HNC). DPD deficiency is a pharmacogenetics syndrome associated with severe/lethal toxicities upon 5-FU or capecitabine intake. We have developed a simple, rapid, and inexpensive functional testing for DPD activity, as a means to identify deficient patients and to anticipate subsequent 5-FU-related toxicities. We present here the impact of fluoropyrimidine dose tailoring based on DPD functional screening in a prospective… 
UPFRONT DPD DEFICIENCY DETECTION TO SECURE 5-FU ADMINISTRATION: PART 2- APPLICATION TO HEAD-AND-NECK CANCER PATIENTS.
TLDR
This study shows that 5-FU-related toxicities can be greatly reduced in routine clinical practice by the upfront detection of DPD deficient patients with simple adaptive dosing strategy.
Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive dosing of 5-FU in patients with digestive cancer.
TLDR
This feasibility study shows how simplified DPD-based adaptive dosing of 5-FU can reduce sharply the incidence of treatment-related severe toxicities while maintaining efficacy as part of routine clinical practice in digestive oncology.
DPYD genotype-guided dose individualization to improve patient safety of fluoropyrimidine therapy: call for a drug label update
The fluoropyrimidine anticancer drugs, especially 5-fluorouracil (5-FU) and capecitabine, are frequently prescribed for several types of cancer, including breast, colorectal, head and neck and
The role of pharmacogenetics in capecitabine efficacy and toxicity.
TLDR
Dose reduction of fluoropyrimidines based on the presence of DPYD variants *2A (rs3918290), *13 (rs55886062), -2846A>T (rs67376798) and -1236G>A/HapB3 (rs56038477) has already been recommended and other variants merit further validation to establish their definite role in explanation of interindividual differences in the outcome of capecitabine-based therapy.
Routine dihydropyrimidine dehydrogenase testing for anticipating 5-fluorouracil-related severe toxicities: hype or hope?
TLDR
This review covers the limits and achievements of the various strategies proposed so far for determining DPD status in patients scheduled for 5-FU therapy and technical consensus on the best way to identify patients with DPD deficiency before administrating5-FU is far from being achieved.
Screening for dihydropyrimidine dehydrogenase deficiency to prevent severe 5-fluorouracil and capeciatbine-associated toxicity
TLDR
A number of phenotype-based screening approaches to detect DPD-deficient patients warrant further clinical validation and appear to be well suited for clinical laboratories and which are an attractive option for monitoring of the DPD status.
5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases
TLDR
5-FU standard dosage administration may lead to strong overexposure, responsible for the severe toxicities observed, including the neurological features, implies that DPD deficiency can cause neurotoxicity in 5-FU-treated patients and advocates for the prospective screening of D PD deficiency before starting any 5-fu-containing chemotherapy so as to prevent such side effects in the future.
Improving safety of fluoropyrimidine chemotherapy by individualizing treatment based on dihydropyrimidine dehydrogenase activity - Ready for clinical practice?
TLDR
The evidence on clinical validity and utility of strategies available to clinicians to identify patients at risk of developing severe and potentially fatal toxicity as a result of DPD deficiency are critically reviewed.
Pharmacogenomics of fluorouracil-based chemotherapy toxicity
TLDR
Future approaches using genome-wide association analyses may help in identifying additional candidate genes causally involved in the path mechanisms of 5-FU-related toxicity.
Detecting DPD deficiency: when perfect is the enemy of good
TLDR
This new work illustrates how ensuring safe 5-FU administration by upfront screening of DPD status remains a challenging issue in the second decade of this century, i.e. nearly 60 years after that this drug has been first approved in oncology and more than 25 years after the first concerns regarding DPD-related toxicities were raised.
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