Introduction The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion. Patients and methods The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes. Results A significant reduction in the viral load was observed (p < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized. Conclusion Results do not prove the use of domperidone as antiviral in patients with COVID-19.

ObjectiveTo determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia.DesignEvaluator blinded, randomised controlled trial.Setting16 clinical sites across 11 European countries, January 2016 to 31 October 2019.Participants1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls).InterventionsThe multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months.Main outcome measuresThe primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes.ResultsMean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34).ConclusionsA multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people.Trial registrationClinicalTrials.gov NCT02582138.

Acute lymphoblastic leukemia (ALL) is a rare, acute, rapidly progressing, and life-threatening form of cancer involving lymphoblasts. Pegaspargase, in which the immunogenicity of the native E.coli asparaginase enzyme is masked by conjugation with a polyethylene glycol group, has equivalent event free survival and overall survival as native E.coli asparaginase, elicits fewer hypersensitivity reactions necessitating an treatment switch to Erwinia derived asparaginase (Erwinase®) and requires fewer injections.

Colorectal cancer (CRC) is one of the most common forms of cancer, with an estimated 1.36 million new cases and almost 700,000 deaths annually. Approximately 21% of patients with CRC have metastatic disease at diagnosis. The objective of this article is to review the literature on the efficacy and safety of oral drugs available for the treatment of metastatic colorectal cancer (mCRC). Several such drugs have been developed, and fluoropyrimidines are the backbone of chemotherapy in this indication. They exert their antitumour activity by disrupting the synthesis and function of DNA and RNA. Oral fluoropyrimidines include prodrugs capecitabine, tegafur, eniluracil/5-fluorouracil, tegafur/uracil, tegafur/gimeracil/oteracil and trifluridine/tipiracil (FTD/TPI). Oral drugs offer several advantages over injectable formulations, including convenience, flexibility, avoidance of injection-related adverse events (AEs) and, in some circumstances, lower costs. However, oral drugs may not be suitable for patients with gastrointestinal obstruction or malabsorption, they may result in reduced treatment adherence and should not be co-administered with drugs that interfere with absorption or hepatic metabolism. Oral fluoropyrimidines such as capecitabine, as monotherapy or in combination with oxaliplatin, irinotecan or bevacizumab, are as effective as intravenous 5-fluorouracil (5-FU) in first-line treatment of mCRC. Other oral fluoropyrimidines, such as FTD/TPI, are effective in patients with mCRC who are refractory, intolerant or ineligible for 5-FU. In addition, oral fluoropyrimidines are used in adjuvant treatment of mCRC. Regorafenib is an oral multikinase inhibitor used in patients in whom several previous lines of therapy have failed. Frequent AEs associated with oral drugs used in the treatment of CRC include hand-foot syndrome and gastrointestinal and haematological toxicities.

Few treatment options exist for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who fail first- and second-line therapies. Pixantrone is a novel aza-anthracenedione agent with reduced potential for cardiotoxicity but maintained anti-tumour activity relative to anthracyclines. The current retrospective, observational, real-life study was undertaken in 79 patients who received pixantrone monotherapy for multiply R/R aggressive B-cell NHL in Spain and Italy. Before pixantrone, patients had received a median of 3 prior therapies and 84.6% of them were refractory to the last regimen. Median progression-free survival (mPFS) was 2.8months (95% confidence interval [CI] 2.1-3.6) and median overall survival (mOS) was 4.0months (95%CI 5.6-7.9), with an objective response rate (ORR) of 29% (complete remission [CR]: 13.2%, partial remission [PR]: 15.2%). Patients receiving ≥2 cycles of pixantrone showed mPFS and mOS of 3.1 and 6.0months, respectively, and an ORR of 36.8% (CR: 17.5%, PR: 19.3%). Overall, 63.3% of patients reported ≥1 adverse event (AE), most commonly haematological AEs. One patient developed grade 2 sinus tachycardia. Pixantrone was effective and well tolerated in a real-world population of multiply R/R patients with aggressive B-cell NHL, many of whom had very poor prognostic factors.

Outcomes for patients with non-Hodgkin’s lymphoma (NHL) that proves refractory to treatment remain poor. Treatment of such patients is individualized and can include enrolment in a clinical trial of novel agents or use of one of a wide array of drug regimens. Initial treatment with anthracyclines such as doxorubicin limits options at later stages of treatment because of anthracycline-related cumulative cardiotoxicity. The aza-anthracenedione pixantrone was developed to reduce the likelihood of cardiotoxicity without compromising efficacy and is currently conditionally approved for use as monotherapy in patients with multiply-relapsed or refractory aggressive B cell NHL. The use of pixantrone in combination therapy, often to replace doxorubicin or mitoxantrone, has or is currently being investigated in numerous studies in patients with aggressive or indolent NHL and is the focus of this review. These include the R-CPOP regimen (rituximab, cyclophosphamide, pixantrone, vincristine, prednisone) for aggressive NHL in the first-line setting, including a study in elderly patients with limited cardiac function, and for patients with relapsed NHL with prior anthracycline exposure; the PSHAP regimen (pixantrone, cytarabine, prednisone, cisplatin), also in the latter setting; the PREBen/PEBen regimen (pixantrone, bendamustine and etoposide with or without rituximab) as salvage therapy; and pixantrone in combination with fludarabine, dexamethasone, and rituximab (FPD-R) for relapsed indolent NHL.

BACKGROUND: The objective of this study was to evaluate the effectiveness and safety of pixantrone as a rescue treatment for NHL patients in a real world population in Spain and Italy as data on the use of this drug in everyday clinical practice is still scarce.METHODS: The study included patients aged ≥18 years with histologically proven relapsed or refractory B-cell aNHL who were treated according to pixantrone's product information. Primary endpoint was progression-free survival (PFS). Secondary endpoints included the proportion of patients with complete response (CR), partial response (PR), overall response rate (ORR), overall survival (OS), as well as safety.RESULTS: 79 patients were included in 52 centers. At diagnosis, mean age was 65 years (95% CI 62-68) and 83% had ECOG 0-1. At pixantrone treatment initiation, 82% of patients presented Ann Arbor stage III-IV, and 64% an International Prognostic Index (IPI) Score ≥3; 85% were refractory and 15% relapsed. Median number of previous therapies was 3 (range 1-5). Patients received a median of two cycles of pixantrone (range 1-6). ORR was 29% with 13.2% CR and 15.8% PR. Median PFS and OS were 2.8 months (95% CI 2.1-3.6) and 4 months (95% CI 3.6-4.4), respectively. There was a trend towards better PFS in relapsed vs refractory patients (12.5 vs 2.6 months, respectively, p=0.059). Patients who received two or more cycles of pixantrone had 38% ORR (CR 17.5%; PR 19.3%). Adverse reactions to pixantrone were reported in 63% of patients. The most frequent toxicities were hematological (67.1%) and gastrointestinal (12%). No febrile neutropenia or clinical cardiotoxicity was reported.CONCLUSIONS: Although a high percentage of patients with very poor prognostic factors was included in this study (82% Ann Harbor III-IV, 63% IPI ≥3, and 85% refractory), treatment with pixantrone appears to be effective. There was a trend to better efficacy in terms of PFS in relapsed vs refractory patients. In those patients who received ≥2 cycles, pixantrone was more effective compared to those who received less than two cycles, with ORR similar to the pivotal study. Pixantrone treatment resulted active and well tolerated in real world clinical practice.Keywords: Refractory non-Hodgkin lymphoma; Relapsed non-Hodgkin lymphoma; Salvage therapy; pixantrone. DisclosuresSancho:Roche: Speakers Bureau; Janssen: Speakers Bureau; Kern Pharma: Speakers Bureau; Roche: Honoraria; Gilead: Honoraria; Celgene: Speakers Bureau; Mundipharma: Speakers Bureau; Sanofi: Speakers Bureau; Servier: Speakers Bureau; Bristol-Myers: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees. Grasso Cicala:Servier: Employment. Spione:Servier: Employment. Zinzani:PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Speakers Bureau.

Abstract Introduction:There is an unmet need for rescue treatment of Non-Hodgkin Lymphoma (NHL) patients who are refractory to initial treatment or relapse after immuno-chemotherapy or after receiving a transplant. Pixantrone is a novel aza-anthracenedione structurally different to anthracyclines and anthracenediones which is thought to be associated with reduced anthracycline-related cardiotoxicity due to a purported reduction in free-radical formation and cardiotoxic alcohols. Due to the lack of Real World Data in patients treated with pixantrone, we perform this study with the objective to evaluate the effectiveness and safety of the drug in a patient's population from Spain and Italy. Methods: An observational retrospective registry of patients was designed. Data were collected from across all centres that have treated at least one patient with pixantrone (one cycle or more) in Spain and from selected centres in Italy. Eligible patients were at least 18 years old, had histologically proven relapsed or refractory aggressive B-cell NHL and had to be treated according to pixantrone product information (SmPC). Informed consent was obtained from patients still alive when the study was initiated. Pixantrone was administered as monotherapy (50 mg/m2 on days 1, 8 and 15 of a 28 days cycle). Clinical baseline characteristics at the time of starting pixantrone were collected: age, gender, international prognostic index (IPI), Eastern Cooperative Oncology Group (ECOG) performance status, extranodal disease, B symptoms and Ann Arbor stage. Details on prior therapy before pixantrone were collected, including transplantation, radiotherapy, and chemotherapy. Type of regimen, duration, best Overall Response Rate (ORR) and rituximab use were registered for the last therapeutic treatment received. Pixantrone treatment specifications as treatment duration, dose delays and dose reductions, ECOG and best outcome were collected. Follow up data after pixantrone treatment and safety information were also requested. Primary endpoint was the Progression Free Survival (PFS). Secondary endpoints included: the proportion of patients who reached a complete response (CR) after pixantrone treatment; ORR and OS. This study is ongoing and recruiting patients in Spain and Italy. Results: In this preliminary analysis 49 patients were included in 31 centers. It is expected to include 90 patients until final database closure. The key baseline characteristics of analyzed patients are outlined in Table 1. The mean age at diagnosis was 65 years (95% CI 61-70). The median number of cycles of treatment with pixantrone was 2 (range, 1-6). Twenty seven patients (58.7%) died in the follow-up up to date. Data on ORR, PFS, and OS will be detailed in the final report, expected in December, 2017. Until now, related or possibly related to pixantrone adverse reactions (AR) were reported in 28 of 38 patients (73.7%). The most common reported adverse reactions were hematological (58.7%), being gastrointestinal adverse reactions the most common non-hematological toxicity reported (10.7%). and administration-site reactions (10.7%). Regarding the ARs severity, Grade 2 were the most frequently reported (36%), followed by Grade 3 (21.3%) and Grade 4 (18.6%).No cardiotoxicity has been reported. Conclusion: These preliminary results of pixantrone treatment in real world clinical practice showed that pixantrone was well tolerated with no evidence of cardiac toxicity. The effectiveness of pixantrone in this study will be confirmed with the future final registry results. Download : Download high-res image (197KB) Download : Download full-size image Disclosures Zinzani: Janssen: Consultancy; Lundbeck: Consultancy; Gilead Sciences: Consultancy; Roche: Consultancy; Celgene: Consultancy; Mundipharma: Consultancy; Takeda: Consultancy; Verastem: Consultancy; Sandoz: Consultancy; Bristol-Myers Squibb: Consultancy; Merck: Consultancy; Servier: Consultancy; Nordic Nanovector: Consultancy; Astellas: Consultancy. Navarro: Laboratorios Servier: Consultancy. Sancho: Celgene: Honoraria; Gilead: Honoraria; Laboratorios Servier: Consultancy; Janssen: Honoraria; Mundipharma: Honoraria; Roche: Honoraria; Kern Pharma: Honoraria. Soler: Laboratorios Servier: Consultancy. Grasso Cicala: Laboratorios Servier: Employment. Yapur: Laboratorios Servier: Employment. Spione: Servier Italy: Employment.

This is a descriptive, transversal and multicenter study using self-administered surveys concurrently to collect the opinions of two groups (psychiatrists and patients) and discuss their disagreements.The scope of study are hospital services, outpatient centres, individual professional consultation and other assistance system, public or private, which provides psychiatric care in Spain. Participated in this study 319 psychiatrists and 957 patients with the diagnosis of depression, stratified by autonomous communities. The populations they are intended to infer the results of this study were all patients diagnosed with depression and antidepressant treatment, and the group of specialists in psychiatry responsible for clinical monitoring at the national level.In the study sample, depressive symptoms related to circadian rhythms are very common: they are experienced by more than 65% of patients surveyed, except the “early morning awakening insomnia” (54%) and “fatigue, anergy and unresponsiveness” (37%). In general, and endorsing the study hypothesis, the prevalence of almost all analysed depressive symptoms is significantly underestimated by psychiatrists about the perception of the patients themselves. Only the presence of “fatigue, anergy and unresponsiveness” is more often observed by professionals than by patients, perhaps by nature be of particular somatic symptoms that may suggest to the clinician to rule out underlying organic pathology.In light of the results presented it is concluded that disturbances in circadian rhythms are core aspects of depression and frequent cause of key symptoms and residual symptoms of patients in treatment. These disorders appear to be underestimated by professionals and only partially solved with existing antidepressant drugs.

This is a descriptive, transversal and multicenter study using self-administered surveys concurrently to collect the opinions of two groups (psychiatrists and patients) and discuss their disagreements. The scope of study are hospital services, outpatient centers, individual professional consultation and other assistance system, public or private, which provides psychiatric care in Spain. Participated in this study 319 psychiatrists and 957 patients with the diagnosis of depression, stratified by autonomous communities. The populations they are intended to infer the results of this study were all patients diagnosed with depression and antidepressant treatment, and the group of specialists in psychiatry responsible for clinical monitoring at the national level. In the study sample, depressive symptoms related to circadian rhythms are very common: they are perceived by more than 65% of patients surveyed, except the «early morning awakening insomnia» (54%) and «fatigue, anergy and unresponsiveness» (37%). In general, and endorsing the study hypothesis, the prevalence of almost all analyzed depressive symptoms is significantly underestimated by psychiatrists about the perception of the patients themselves. Only the presence of «fatigue, anergy and unresponsiveness» is more often observed by professionals than by patients, perhaps by nature be of particular somatic symptoms that may suggest to the clinician to rule out underlying organic pathology. In light of the results presented it is concluded that disturbances in circadian rhythms are core aspects of depression and frequent cause of key symptoms and residual symptoms of patients in treatment. These disorders appear to be underestimated by professionals and only partially solved with existing antidepressant drugs.