Repurposing anticancer drugs for the management of COVID-19

Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion and thus is regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so far. Drug repurposing represents an enthusiastic mechanism to use approved drugs outside the scope of their original indication and accelerate the discovery of new therapeutic options. With the emergence of COVID-19, drug repurposing has been largely applied for early clinical testing. In this review, we discuss some repurposed anticancer drugs for the treatment of COVID-19, which are under investigation in clinical trials or proposed for the clinical testing.info:eu-repo/semantics/publishedVersio

Anthracycline and concurrent radiotherapy as adjuvant treatment of operable breast cancer: a retrospective cohort study in a single institution

<p>Abstract</p> <p>Background</p> <p>Concurrent chemoradiotherapy (CCRT) after breast surgery was investigated by few authors and remains controversial, because of concerns of toxicity with taxanes/anthracyclines and radiation. This treatment is not standard and is more commonly used for locally advanced breast cancer. The aim of our study was to evaluate the efficacy and safety of the concomitant use of anthracycline with radiotherapy (RT).</p> <p>Findings</p> <p>Four hundred women having operable breast cancer, treated by adjuvant chemotherapy (CT) and RT in concomitant way between January 2001 and December 2003, were included in this retrospective cohort study. The study compares 2 adjuvant treatments using CCRT, the first with anthracycline (group A) and the second with CMF (group B). The CT treatment was repeated every 21 days for 6 courses and the total delivered dose of RT was 50 Gy, divided as 2 Gy daily fractions. Locoregional recurrence free (LRFS), event free (EFS), and overall survivals (OS) were estimated by the Kaplan-Meier method. The log-rank test was used to compare survival events. Multivariate Cox-regression was used to evaluate the relationship between patient characteristics, treatment and survival.</p> <p>In the 2 groups (A+B) (n = 400; 249 in group A and 151 in group B), the median follow-up period was 74.5 months. At 5 years, the isolated LRFS was significantly higher in group A compared to group B (98.7% vs 95.3%; hazard ratio [HR] = 0.258; 95% CI, 0.067 to 0.997; log-rank <it>P </it>= .034). In addition, the use of anthracycline regimens was associated with a higher rate of 5 years EFS (80.4% vs 75.1%; HR = 0.665; 95% CI, 0.455 to 1.016; log-rank <it>P </it>= .057). The 5 years OS was 83.2% and 79.2% in the anthracycline and CMF groups, respectively (HR = 0.708; 95% CI, 0.455 to 1.128; log-rank <it>P </it>= .143). Multivariate analysis confirmed the positive effect of anthracycline regimens on LRFS (HR = 0.347; 95% CI, 0.114 to 1.053; log-rank <it>P </it>= .062), EFS (HR = 0.539; 95% CI, 0.344 to 0.846; <it>P </it>= 0.012), and OS (HR = 0.63; 95% CI, 0.401 to 0.991; <it>P </it>= .046). LRFS, EFS and OS were significantly higher in the anthracycline group where the patients (n = 288) received more than 1 cycle of concurrent CT (<it>P </it>= .038, <it>P </it>= .026 and <it>P </it>= .038, respectively). LRFS and EFS were significantly higher in the anthracycline group within the BCT subgroup (<it>P </it>= .049 and <it>P </it>= .04, respectively). There were more hematologic, and more grade 2/3/4 skin toxicity in the anthracycline group.</p> <p>Conclusions</p> <p>After mastectomy or BCT, the adjuvant treatment based on anthracycline and concurrent RT reduced breast cancer relapse rate, and significantly improved LRFS, EFS and OS in the patients receiving more than 1 cycle of concurrent CT. There were more hematologic and non hematologic toxicities in the anthracycline group.</p

Male breast cancer: a report of 127 cases at a Moroccan institution

Background: Male breast cancer (MBC) is a rare disease representing less than 1% of all malignancies in men and only 1% of all incident breast cancers. Our study details clinico-pathological features, treatments and prognostic factors in a large Moroccan cohort. Findings: One hundred and twenty-seven patients were collected from 1985 to 2007 at the National Institute of Oncology in Rabat, Morocco. Median age was 62 years and median time for consultation 28 months. The main clinical complaint was a mass beneath the areola in 93, 5% of the cases. Most patients have an advanced disease. Ninety-one percent of tumors were ductal carcinomas. Management consisted especially of radical mastectomy; followed by adjuvant radiotherapy and hormonal therapy with or without chemotherapy. The median of follow-up was 30 months. The evolution has been characterized by local recurrence; in twenty two cases (17% of all patients). Metastasis occurred in 41 cases (32% of all patients). The site of metastasis was the bone in twenty cases; lung in twelve cases; liver in seven case; liver and skin in one case and pleura and skin in one case. Conclusion: Male breast cancer has many similarities to breast cancer in women, but there are distinct features that should be appreciated. Future research for better understanding of this disease at national or international level are needed to improve the management and prognosis of male patients

Factors of interrupting chemotherapy in patients with Advanced Non-Small-Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Little is known about prognosis of metastatic patients after receiving a first-line treatment and failure. Our group already showed in pre-treated patients enrolled in phase I clinical trials that a performance status (PS) > 2 and an LDH > 600 UI/L were independent prognostic factors. In this prospective study, which included 45 patients, we identified clinical and biological variables as outcome predictors in metastatic Non-Small Cell lung cancer after first line chemotherapy were identified.</p> <p>Findings</p> <p>Forty-five patients that were previously treated for metastatic disease from 12/2000 to 11/2005 in the comprehensive cancer centre (Centre Léon Bérard). Clinical assessment and blood parameters were recorded and considered. Patient prognostic factors for overall survival (OS) with a 0.05-significance level in univariate analysis were entered in a multivariate Cox model for further analysis.</p> <p>Patients' median age was 58.5 years (range: 37 - 76). Sixty two percent of the patients were PS = 0 or 1. After inclusion, nine patients received second-line (22.5%), and two received third-line chemotherapy (5%). Univariate analysis showed that the factors associated with reduced OS were: PS > 2, weight loss >10%, more than one line of chemotherapy treatment and abnormal blood parameters (hemoglobin (Hb), platelet and neutrophils counts). Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for low overall survival. According to the presence of none (33%), 1 (37%) and 2 (30%) prognostic factors, median OS were 12, 5 and 2 months respectively.</p> <p>Conclusion</p> <p>From this prospective study, both PS and anemia were found as independent determinants of survival, we found that both PS and anemia were independent determinants of survival. The combination of poor PS and anemia is an effective strategy to predict survival in the case of patients with metastatic NSCLC receiving further treatment after the first line.</p

Symptomatic hypopituitarism revealing primary suprasellar lymphoma

<p>Abstract</p> <p>Background</p> <p>The most common cause of hypopituitarism is pituitary adenoma. However, in the case of suprasellar masses different etiologies are possible. We report an unusual case of primary suprasellar lymphoma presented with hypopituitarism.</p> <p>Case presentation</p> <p>A 26 year old woman presented with amenorrhea, galactorrhea and neurological disorders. Also, the laboratory work-up revealed partial hypopituitarism. The magnetic resonance imaging of the head showed a suprasellar mass. A presumptive diagnosis of granulomatous processes was made and the patient was given steroid therapy. Repeated brain MRI detected new lesions in the brain with regression of the suprasellar mass. Stereotactic biopsy of the paraventricular lesion revealed the diagnosis of B-cell lymphoma.</p> <p>Conclusion</p> <p>This case presentation reports a rare cause of hypopituitarism. Primary suprasellar lymphoma is extremely rare and represented a real diagnostic challenge. Besides, suprasellar masses are varied in aetiology and can present diagnostic problems for a radiologist. Also, because of the increased incidence of PCNSL, lymphoma must be kept in mind in the differential diagnosis of lesions in the suprasellar region.</p

Tolérance de l’évérolimus en pratique clinique: étude retrospective

L´évérolimus est un inhibiteur mTOR ayant démontré une activité clinique dans plusieurs tumeurs solides notamment dans le cancer du rein après une première ligne à base d´un TKI anti VEGF et dans le cancer du sein en association avec l´exemesthane après échec d´un antiaroamatase. L´objectif de ce travail est d´analyser le profil de tolérance de l´évérolimus dans le cancer du sein et le cancer du rein en pratique clinique. Il s´agit d´une étude rétrospective portant sur les patients suivis pour cancer du sein et cancer du rein durant la période s´étendant de janvier 2008 à janvier 2015. Tous les patients ont reçu l´évérolimus à la dose quotidienne de 10 mg seul ou en association avec l´exemesthane pour le cancer du sein. Les effets indésirables ont été gradés selon la classification du&nbsp;National Cancer Institute Common Terminology Criteria for Adverses version 4.0 (NCI-CTCAE). Au total 100 patients ont été inclus: 76 patientes avec cancer du sein et 24 patients avec cancer rénal. La durée médiane de traitement était estimée à 5,7 mois. Le traitement a été arrêté dans plus de 70% des cas pour intolérance. Les principaux effets indésirables avec une incidence de plus de 30% pour tous les grades étaient la mucite, le rash, la fatigue, l´anémie, la lymphopénie, l´hyperglycémie,l´hyperlipidémie et les infections. Les toxicités grade 3-4 avec incidence élevée étaient la mucite, la pneumopathie non infectieuse et les infections. Le taux d´arrêt du traitement pour intolérance reste élevé en comparaison avec les données de la literature. Une attention particulière doit être accordée à la mucite, l´effet immunosuppresseur de traitement et la pneumopathie non infectieuse et ce dès le début du traitement