Chantal Barin-Le Guellec1, Claire Lafay-Chebassier2, Isabelle Ingrand3, Jean-François Tournamille4, Adeline Boudet5, Mary-Christine Lanoue5, Gautier Defossez6, Pierre Ingrand6, Marie-Christine Perault-Pochat2, Marie-Christine Etienne-Grimaldi7. 1. Laboratoire de Biochimie et Biologie Moléculaire, Unité de Pharmacogénétique, CHU de Tours, France; INSERM U1248-IPPRIT, Université, CHU de Limoges, France. Electronic address: chantal.barin-leguellec@univ-tours.fr. 2. Service de Pharmacologie Clinique et Vigilances, Université, CHU de Poitiers, France; INSERM U1084-LNEC/ INSERM CIC 1402, Université, CHU de Poitiers, France. 3. Service de Pharmacologie Clinique et Vigilances, Université, CHU de Poitiers, France; Unité d'Epidémiologie et Biostatistique, Registre Général des Cancers Poitou-Charentes, INSERM CIC 1402, Université, CHU de Poitiers, France. 4. Unité de Biopharmacie Clinique Oncologique, Pharmacie, CHU de Tours, France. 5. OMEDIT Région Centre, CHU de Tours, France. 6. Unité d'Epidémiologie et Biostatistique, Registre Général des Cancers Poitou-Charentes, INSERM CIC 1402, Université, CHU de Poitiers, France. 7. Centre Antoine Lacassagne, Nice, France.
Abstract
AIMS: Despite fluoropyrimidines (FPs) constituting the main component of the chemotherapy combination protocols in 50% of chemotherapies for solid tumour treatments, incidence data for FP-related toxicity are poorly documented in real life. This study evaluated the number of patients receiving FP-based chemotherapies in France, along with the true incidence of FP-related serious adverse effects (SAEs) before the recent mandatory dihydropyrimidine dehydrogenase (DPD)-screening was introduced by French health authorities, DPD being the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. METHODS: Exhaustive data on the number of patients treated with FP-based chemotherapy in 2013-2014 were collected in the Centre-Val de Loire region of France. True incidence of SAEs was extracted from a cohort of 513 patients with incident solid tumours receiving first-line FP-based chemotherapy. RESULTS: After extrapolation at national level, we estimated that 76,200 patients are currently treated annually with 5FU (53,100 patients, 62% digestive system-related versus 26% breast cancers versus 12% head and neck cancers) or capecitabine (23,100 patients, 45% digestive system-related versus 37% breast cancers versus 18% non-documented). Earlier (in the first two cycles) the SAE incidence rate was 19.3% (95% confidence interval (CI) 16-23%) including one toxic death (0.2%, 95%CI 0-1%). SAE incidence rate was 32.2% (95%CI 28-36%) over the first 6 months of treatment. Incidence of death, life-threatening prognosis or incapacity/disability was 1.4% (95%CI 0.4-2.4%) and 1.6% (95%CI 0.5-2.6%) during first two cycles and first 6 months, respectively. CONCLUSION: These data highlight the significant public health issue related to FP toxicity, with around 1200 patients developing FP-related life-threatening prognosis or incapacity/disability annually in France, including 150 toxic deaths. It is hoped that DPD-deficiency screening will reduce such iatrogenic events and eradicate toxic deaths.
AIMS: Despite fluoropyrimidines (FPs) constituting the main component of the chemotherapy combination protocols in 50% of chemotherapies for solid tumour treatments, incidence data for FP-related toxicity are poorly documented in real life. This study evaluated the number of patients receiving FP-based chemotherapies in France, along with the true incidence of FP-related serious adverse effects (SAEs) before the recent mandatory dihydropyrimidine dehydrogenase (DPD)-screening was introduced by French health authorities, DPD being the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. METHODS: Exhaustive data on the number of patients treated with FP-based chemotherapy in 2013-2014 were collected in the Centre-Val de Loire region of France. True incidence of SAEs was extracted from a cohort of 513 patients with incident solid tumours receiving first-line FP-based chemotherapy. RESULTS: After extrapolation at national level, we estimated that 76,200 patients are currently treated annually with 5FU (53,100 patients, 62% digestive system-related versus 26% breast cancers versus 12% head and neck cancers) or capecitabine (23,100 patients, 45% digestive system-related versus 37% breast cancers versus 18% non-documented). Earlier (in the first two cycles) the SAE incidence rate was 19.3% (95% confidence interval (CI) 16-23%) including one toxic death (0.2%, 95%CI 0-1%). SAE incidence rate was 32.2% (95%CI 28-36%) over the first 6 months of treatment. Incidence of death, life-threatening prognosis or incapacity/disability was 1.4% (95%CI 0.4-2.4%) and 1.6% (95%CI 0.5-2.6%) during first two cycles and first 6 months, respectively. CONCLUSION: These data highlight the significant public health issue related to FPtoxicity, with around 1200 patients developing FP-related life-threatening prognosis or incapacity/disability annually in France, including 150 toxic deaths. It is hoped that DPD-deficiency screening will reduce such iatrogenic events and eradicate toxic deaths.
Authors: Mirjam de With; Jonathan Knikman; Femke M de Man; Carin A T C Lunenburg; Linda M Henricks; André B P van Kuilenburg; Jan G Maring; Maurice C van Staveren; Niels de Vries; Hilde Rosing; Jos H Beijnen; Dick Pluim; Anil Modak; Alex L T Imholz; Ron H N van Schaik; Jan H M Schellens; Hans Gelderblom; Annemieke Cats; Henk-Jan Guchelaar; Ron H J Mathijssen; Jesse J Swen; Didier Meulendijks Journal: Clin Pharmacol Ther Date: 2022-05-04 Impact factor: 6.903