Lucie-Marie Scailteux

Mortality, cardiovascular risk, and androgen deprivation therapy for prostate cancer: A systematic review with direct and network meta-analyses of randomized controlled trials and observational studies

AbstractAndrogen deprivation therapy (ADT) is a cornerstone therapy for advanced prostate cancer (PCa). We hypothesized that cardiovascular (CV) risk is different across the various ADT modalities to compare their effects on CV morbidity and mortality, and all-cause mortality in patients with PCa. To investigate more in depth potential CV risk heterogeneity focusing on coronary (main outcome) and cerebrovascular risk, CV, and overall mortality. We performed a Medline and Embase query, without language restriction, since 1950 up to July 2014. We included randomized controlled trials (RCTs) and observational studies providing that they compared at least 1 ADT modality to another one or to placebo and they gave data on CV event or all-cause mortality. Sixty-eight studies out of 3419 met our eligibility criteria. Eleven observational studies were analyzed. Direct meta-analyses showed that antiandrogen was associated with a 30% decrease risk for myocardial infarction (MI) compared to GnRH agonists (RR, 0.70 [0.54–0.91]); combined androgen blockade (CAB) was associated with a 10% increase risk for stroke when compared to antiandrogen (RR, 1.10 [1.02–1.19]). With regard to RCTs, 57 were included: direct meta-analyses suggested that CAB was associated with a 10% decrease of all-cause mortality when compared to GnRH agonist (RR, 0.90 [0.82–1.00]). Network analysis could only be performed for all-cause mortality and it remains difficult to disentangle benefit (positive impact on cancer survival) and risk (including CV risk). The impact of the ADT modalities on CV morbidity remains difficult to quantify and more detailed prospective collection is required. Registration: PROSPERO, CRD42014010598.

Rationale and design of the CANARI study: a case-control study investigating the association between prostate cancer and 5 alpha-reductase inhibitors for symptomatic benign prostate hypertrophy by linking SNIIRAM and pathology laboratories in a specific region in France

Benign prostate hypertrophy (BPH) could be associated with low urinary symptoms requiring medical treatment: 5‐alpha‐reductase inhibitors (5‐ARI) or ɑ‐blockers. Two clinical trials investigating 5‐ARI use in prostate cancer (PCa) primary prevention highlighted a potential safety signal with an increased risk of high‐grade PCa. Later observational studies failed to show similar results but have some limits. This paper focuses on describing the protocol of the CANARI study and its feasibility, as regards the matching process of two pseudo‐anonymous databases. The study concerned patients living in the Brittany region (France) between 2010 and 2013. We designed a case–control study nested within a cohort of men treated by medical drugs licensed for symptomatic BPH between 2010 and 2011. Cases were patients with incident PCa diagnosed between 2012 and 2013 identified through French Health database (SNIIRAM). Gleason score was searched through Brittany pathology laboratories. Controls were patients without PCa diagnosis. Local pathology laboratories database was constituted in Brittany, gathering Gleason scores. No unique identification number is available in France; linkage of SNIIRAM and Brittany pathology laboratories database was made by deterministic matching. We matched 859 cases to Gleason grading (119 had Gleason score ≥8 and 740 had Gleason <8); around 22% of cases received 5‐ARI and 78% α‐blockers or phytotherapy. The CANARI study investigated in a population of men treated for BPH the risk of PCa with 5‐ARI, according to Gleason grade thanks to SNIIRAM database enriched by local pathological results.

Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high grade prostate cancer: a French population-based study

To assess the association between 5α‐reductase inhibitor (5‐ARI) use and high grade (Gleason score 8–10) prostate cancer.

MP57-11 ANDROGEN-DEPRIVATION THERAPY AND CARDIOVASCULAR RISK (ADTCR): A NATIONWIDE POPULATION-BASED COHORT STUDY

RESULTS: Among 2439 patients, cumulative exposure was greatest for docetaxel (n1⁄41886 (77.3%); 11,436 person-months), followed by abiraterone (n1⁄4893 (36.6%); 5143 person-months), enzalutamide (n1⁄452 (2.1%); 351 person-months) and cabazitaxel (n1⁄418 (0.7%); 61 person-months). Abiraterone exposure was not significantly associated with any-cause (HR 0.88, 95% CI 0.72-1.07) or treatment-related (HR 1.09, 95% CI 0.87-1.37) hospitalizations or ER visits. Enzalutamide was not significantly associated with anycause (HR 1.20, 95% CI 0.69-2.07) or treatment-related (HR 0.85, 95% CI 0.43-1.68) toxicity. Docetaxel exposure was associated with a significantly increased risk of any-cause (HR 1.29, 95% CI 1.151.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicity. Cabazitaxel exposure was also associated with treatment-related (HR 5.94, 95% CI 1.87-18.92) but not any-cause (HR 2.37, 95% CI 0.599.63) toxicity. Patients who began CRPC treatment after the introduction of oral therapies had improved overall survival compared with those treated prior to their introduction (aHR 0.70, 95% CI 0.64-0.77). CONCLUSIONS: Among patients with metastatic CRPC, treatment with chemotherapy (docetaxel or cabazitaxel) is associated with an increased risk of hospitalizations and emergency room visits. We failed to show a significantly increased risk for patients treated with oral agents (abiraterone or enzalutamide).

Response to letter – Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Response to letter – Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists Lucie-Marie Scailteux

Adaptation and validation of an adverse drug reaction preventability score for bleeding due to vitamin K antagonists.

AbstractAlthough drug therapy is inherently associated with the risk of adverse drug reactions (ADRs), some of these events are preventable. The estimated proportion of preventable ADRs varies from one study or clinical context to another. Bleeding caused by antithrombotic agents (and particularly vitamin K antagonists, VKAs) constitutes one of the most frequent causes of ADR-related hospitalization.Hence, the objective of the present study was to adapt and validate an ADR preventability score for bleeding due to VKAs and evaluate the preventability of bleeding in 906 consecutive hospitalized, VKA-treated adult patients with a risk of major bleeding (defined as an international normalized ratio ≥5) over a 2-year period. A specific preventability scale for VKA-associated bleeding was developed by adapting a published tool.Overall, 241 of the 906 patients in the study experienced at least 1 VKA-associated bleeding event. The scales reliability was tested by 2 different evaluators. The inter-rater reliability (evaluated by calculation of Cohens kappa) ranged from “good” to “excellent.” Lastly, the validated scale was used to assess the preventability of the VKA-associated bleeding. We estimated that bleeding was preventable or potentially preventable in 109 of the 241 affected patients (45.2%).We have developed a useful, reliable tool for evaluating the preventability of VKA-associated bleeding. Application of the scale in a prospective study revealed that a high proportion of VKA-associated bleeding events in hospitalized, at-risk adult patients were preventable or potentially preventable.