In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3823-3823
Abstract:
Introduction: Fluoropyrimidines (FP) are of major use in treating cancer. Dihydropyrimidine dehydrogenase (DPD) is the main enzyme responsible for FP catabolism. Low DPD activity screening has proven its predictive clinical value in identifying patients at risk for toxicity. However, high DPD activity may translate to decreased FP activation and efficacy. Patients and methods: One hundred and forty-three patients (monocentric retrospective study) underwent a pretreatment assessment of DPD activity in lymphocytes between 01/01/2004 and 20/04/2016. Included patients were male or female, & gt;18 years, FP-treatment-based. Cut-off for DPD activity was assessed using smoothing spline curves. Results: Median patient follow-up was 30 months [CI95%: 27.3-36.2], mean age 63+/-3 years, females accounted for 53%, 90% of patients had a good performance status (0 or 1). Fifty-eight percent of FP indications (65% 5-FU and 35% capecitabine) were adjuvant or neoadjuvant and 42% were prescribed for local or metastatic recurrences. Tolerance was poor for 43% of patients and 49% needed dose reduction. Objective response (complete and partial) was observed in 50% of patients, stable disease in 38% and progression in 12%. No significant correlation was observed between DPD activity and response to treatment. Mean DPD activity (pmol min−1 mg−1 protein) was 0.21+/-0.1 (quartile: [0.001-0.14-0.20-0.28-0.48] ). DPD activity analyzed as a continuous variable was significantly linked to overall survival (OS) (p=0.042) but not with progression-free survival (PFS). The higher the DPD activity, the lower the OS. DPD activity analyzed as a binary variable (cut-off at 0.30) was significantly linked to overall survival (p=0.012) but also with PFS (p=0.016). A Cox regression model for OS and PFS adjusted for age, sex, type of cancer, type of administered FP, and associated surgical or radiotherapy treatment was performed. After adjustment, DPD activity remained significantly linked to OS (p=0.03) and PFS (p=0.021). Conclusions: DPD activity screening could lead to a two-pronged approach: FP dose reduction in the event of low DPD and dose increase for high DPD. Such a strategy needs to be prospectively validated under personalized DPD-based treatment. Note: This abstract was not presented at the meeting. Citation Format: Emmanuel Chamorey, Eric Francois, Marie-Christine Etienne-Grimaldi, Julien Viotti, Frederic Peyrade, Alexandre Bozec, Jean-Marc Ferrero, Renaud Schiappa, Gerard Milano. High intrinsic DPD activity matters too [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3823. doi:10.1158/1538-7445.AM2017-3823
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-3823
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
