Prediction of severe toxicity in adult patients under treatment with 5-fluorouracil: a prospective cohort study
Fluorouracil (5-FU) has long been used for the treatment of gastrointestinal tumors harboring interindividual variability in both the pharmacokinetic and the pharmacogenetic profiles, which in turn may lead to life-threatening toxicities. We carried out a prospective cohort study of adult patients initiating treatment with 5-FU between 2013 and 2015. Primary exposures of interest were the methylenetetrahydrofolate reductase single nucleotide polymorphism in exons 4 and 7 and 5′-untranslated region-thymidylate synthase VNTR genotypes, in addition to baseline clinical and demographic variables. The primary outcome was the time to the occurrence of severe toxicity. We used a Cox regression model to evaluate patients’ survival and toxicity experience and its association with baseline characteristics and a priori determined genetic polymorphisms. A total of 197 patients were included, 40.1% developed severe toxicity during follow-up. Variables that were significantly associated with developing severe toxicity were the European Organization for Research and Treatment of Cancer functional score [hazard ratio (HR)0.98; 95% confidence interval (CI)0.97–0.99]; type of tumor [anus (HR2.50; 95% CI1.07–5.82), head and neck/esophagus/stomach (HR2.95; 95% CI1.64–5.33)] and 5-FU continuous infusion regimens over 4–5 days (HR9.35; 95% CI2.68–32.59). We found a significant association between baseline functional status, type of tumor and continuous infusion regimens and the occurrence of severe toxicity during the follow-up of patients receiving 5-FU. No association was found with the genotypic variants evaluated. Future validation and modeling of an everyday easy-to-use score to predict toxicity among these subgroup of patients remains warranted..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Anti-cancer drugs - 28(2017), 9, Seite 1039-1046 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vázquez, Carolina [VerfasserIn] |
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| Links: |
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| doi: |
10.1097/CAD.0000000000000546 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC1998154475 |
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| 520 | |a Fluorouracil (5-FU) has long been used for the treatment of gastrointestinal tumors harboring interindividual variability in both the pharmacokinetic and the pharmacogenetic profiles, which in turn may lead to life-threatening toxicities. We carried out a prospective cohort study of adult patients initiating treatment with 5-FU between 2013 and 2015. Primary exposures of interest were the methylenetetrahydrofolate reductase single nucleotide polymorphism in exons 4 and 7 and 5′-untranslated region-thymidylate synthase VNTR genotypes, in addition to baseline clinical and demographic variables. The primary outcome was the time to the occurrence of severe toxicity. We used a Cox regression model to evaluate patients’ survival and toxicity experience and its association with baseline characteristics and a priori determined genetic polymorphisms. A total of 197 patients were included, 40.1% developed severe toxicity during follow-up. Variables that were significantly associated with developing severe toxicity were the European Organization for Research and Treatment of Cancer functional score [hazard ratio (HR)0.98; 95% confidence interval (CI)0.97–0.99]; type of tumor [anus (HR2.50; 95% CI1.07–5.82), head and neck/esophagus/stomach (HR2.95; 95% CI1.64–5.33)] and 5-FU continuous infusion regimens over 4–5 days (HR9.35; 95% CI2.68–32.59). We found a significant association between baseline functional status, type of tumor and continuous infusion regimens and the occurrence of severe toxicity during the follow-up of patients receiving 5-FU. No association was found with the genotypic variants evaluated. Future validation and modeling of an everyday easy-to-use score to predict toxicity among these subgroup of patients remains warranted. | ||
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| 700 | 1 | |a Orlova, María |4 oth | |
| 700 | 1 | |a Angriman, Federico |4 oth | |
| 700 | 1 | |a Minatta, José N |4 oth | |
| 700 | 1 | |a Scibona, Paula |4 oth | |
| 700 | 1 | |a Verzura, María A |4 oth | |
| 700 | 1 | |a Jáuregui, Esteban G |4 oth | |
| 700 | 1 | |a Díaz de Arce, Heidy |4 oth | |
| 700 | 1 | |a Pallotta, María G |4 oth | |
| 700 | 1 | |a Belloso, Waldo H |4 oth | |
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