Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Glasdegib 100 mg (oral, QD) was administered continuously in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for 10 per 28 days. Patients (stratified by cytogenetic risk) were randomized (2:1) to receive glasdegib/LDAC or LDAC. The primary endpoint was overall survival. Eighty-eight and 44 patients were randomized to glasdegib/LDAC and LDAC, respectively. Median (80% confidence interval [CI]) overall survival was 8.8 (6.9–9.9) months with glasdegib/LDAC and 4.9 (3.5–6.0) months with LDAC (hazard ratio, 0.51; 80% CI, 0.39–0.67, P = 0.0004). Fifteen (17.0%) and 1 (2.3%) patients in the glasdegib/LDAC and LDAC arms, respectively, achieved complete remission (P < 0.05). Nonhematologic grade 3/4 all-causality adverse events included pneumonia (16.7%) and fatigue (14.3%) with glasdegib/LDAC and pneumonia (14.6%) with LDAC. Clinical efficacy was evident across patients with diverse mutational profiles. Glasdegib plus LDAC has a favorable benefit–risk profile and may be a promising option for AML patients unsuitable for intensive chemotherapy.
We propose a high-dimensional quantum key distribution (QKD) protocol that employs temporal correlations of entangled photons. The security of the protocol relies on measurements by Alice and Bob in one of two conjugate bases, implemented using dispersive optics. We show that this dispersion-based approach is secure against general coherent attacks. The protocol is additionally compatible with standard fiber telecommunications channels and wavelength division multiplexers. We offer multiple implementations to enhance the transmission rate and describe a heralded qudit source that is easy to implement and enables secret-key generation at up to 100 Mbps at over 2 bits per photon.Comment: 5 pages, 3 figures. v2 contains details of security analysis previously left to Supplemental Information (not included in v1
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.
Background: Adjuvant hormonal therapy is crucial in the treatment of estrogen receptor-positive breast cancer. The nonadherence rate to hormonal treatment is reported to be as high as 60%. The goal of this study was to evaluate the factors evoked by the patients as well as the demographic and disease-related factors that could be associated with nonadherence to adjuvant hormonal therapy.Methods: All consecutive patients treated for an estrogen receptor-positive breast cancer who showed up for regular follow-up with a single breast specialist between November 2008 and April 2009 were included in the study. We assessed adherence to hormonal therapy (either with tamoxifen or aromatase inhibitor). Reasons for adherence and nonadherence were collected. Records were also reviewed for demographic and cancer characteristics and for treatment components. Results:We included 161 patients in the study; 150 (93.2%) adhered to hormonal treatment. Side effects and absence of conviction were the main reasons for nonadherence. The importance of the diagnosis of cancer, fear of recurrence and regular follow-up were reported as the main reasons for adherence. Conclusion:Severity of disease and side effects are associated with nonadherence to treatment. Strict follow-up appears to be a necessary adjunct in the adherence to treatment. The association between demographic and cancer characteristics and treatment components needs further investigation. However, these factors may help identify patients at risk of nonadherence and help the oncology team.Contexte : Le traitement hormonal adjuvant est crucial dans le traitement du cancer du sein avec récepteurs estrogéniques positifs. Le taux d'inobservance au traitement hormonal atteint 60 %. Le but de cette étude consiste à évaluer les facteurs évoqués par les patientes ainsi que les facteurs démographiques et pathologiques pouvant être associés à l'inobservance au traitement hormonal adjuvant. Méthodes :Toutes les patientes qui ont été traitées pour cancer du sein avec récep-teurs estrogéniques positifs et suivies régulièrement par un spécialiste du cancer du sein de novembre 2008 à avril 2009 ont été incluses dans l'étude. L'adhérence au traitement hormonal (tamoxifène ou inhibiteur de l'aromatase) a été évaluée. Les dossiers des patientes ont aussi été révisés pour colliger les facteurs démographiques, pathologiques et thérapeutiques. Résultats :Il y a eu 161 patientes; 150 (93,2%) ont suivi le traitement hormonal. Les effets secondaires et l'absence de conviction des patientes face au bénéfice du traitement furent les principales raisons évoquées pour ne pas prendre la médication. L'importance du diagnostic de cancer, la peur de récidive et le suivi régulier furent les principales raisons rapportées pour suivre le traitement.Conclusion : La sévérité de la maladie et les effets secondaires sont associés avec l'inobservance au traitement hormonal. Le suivi rigoureux semble s'avérer nécessaire dans l'observance au traitement des patientes. La relation entre les facteurs démographiques,...
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