[Haemorrhagic complications following ibrutinib intake after dermatological surgery]. / Complication hémorragique secondaire à la prise d'ibrutinib après chirurgie dermatologique.

INTRODUCTION: Ibrutinib is a selective oral inhibitor of Bruton's tyrosine kinase. It is used in haematology to treat lymphoid B disorders. Haemorrhagic complications in dermatological surgery are occasionally associated with the use of anti-platelet and/or anticoagulant medication. Herein, we report a case of haemorrhage under ibrutinib following skin surgery. PATIENTS AND METHODS: A 70-year-old male patient began treatment with ibrutinib for chronic lymphocytic leukaemia had 2 basal cell carcinomas of the face. The next day he had a persistent haemorrhage lasting more than 48h, with no effects on the final scarring result. DISCUSSION: Ibrutinib is a tyrosine kinase inhibitor whose mechanism of action plays a role in platelet adhesion. It is known to cause haemorrhaging, either spontaneously or following invasive procedures, especially at the beginning of treatment. In the case of low-risk haemorrhagic procedures in which bleeding may be controlled by mechanical haemostasis, ibrutinib should be discontinued 3 days before and after surgery. In the event of recent initiation of ibrutinib and in the absence of urgent dermatological management, it is preferable to schedule any surgical procedures 3 months after the start of ibrutinib.

Determinants of the interindividual variability in serum cytidine deaminase activity of patients with solid tumours.

AIMS: Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this interindividual variability. METHODS: From December 2014 to November 2015, 183 patients were prospectively included. Serum CDA activity, biological and clinical characteristics as well as five common single nucleotide polymorphisms (SNPs) in the CDA gene (c.-451C > T, c.-92A > G, c.-33_-31delC, c.79A > C, c.435 T > C) were analysed. Associations between clinical characteristics, pharmacogenetic variants and CDA activity were univariately tested. P < 0.1-candidate variables were analysed through a multivariate analysis. The association between CDA activity and toxicity was assessed for the 56 gemcitabine-treated patients. Intraindividual variability in CDA activity was explored in six pancreatic cancer patients treated with gemcitabine. RESULTS: Median CDA activity was 3.97 U mg-1 (range 1.53-15.49 U mg-1 ). A univariate analysis showed that CDA activity was statistically associated with Eastern Cooperative Oncology Group performance status, mild or severe malnutrition, inflammatory syndrome, leucocyte count, neutrophil count, albumin, C-reactive protein and -c.-33_-31delC single nucleotide polymorphism. A multivariate analysis identified that only neutrophil count (P < 0.0001) and severe malnutrition (P = 0.0278) were independently associated with CDA activity. Low CDA activity (<2 U mg-1 ) was not statistically associated with severe gemcitabine-related toxicities (P = 0.16). A decrease in CDA activity was observed during the longitudinal follow-up of six pancreatic cancer patients treated with gemcitabine (P = 0.03). CONCLUSIONS: These results suggest that neutrophil count and malnutrition should be considered for the interpretation of pretherapeutic CDA activity.