61 research outputs found
Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)
Rehabilitation Interventions for Post-Acute COVID-19 Syndrome: A Systematic Review
Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2–69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had “low risk of bias”, and three were in the “some concerns” category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS
Rehabilitation Interventions for Post-Acute COVID-19 Syndrome: A Systematic Review
Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2–69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had “low risk of bias”, and three were in the “some concerns” category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.</jats:p
Safety and efficacy of tivozanib in first-line metastatic renal cell carcinoma: A multicenter compassionate use study.
632 Background: Tivozanib-TIVO is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR-2, and VEGFR-3. TIVO was recently approved in Europe for the first line treatment of metastatic Renal Cell Carcinoma-RCC after a randomized trial demonstrated improved PFS and different safety profile compared to sorafenib. Methods: Retrospective analysis of safety and activity of TIVO administered within a compassionate use program to pts with metastatic RCC with no prior systemic treatment. Results: From Aug 2018 to Apr 2019, 64 pts have started TIVO at 1,34 mg daily (three weeks on, 1 week off) in 9 Italian Oncology Units. Median age was 67.5 years (range 40 to 85), 61% males, median creatinine clearance 63 ml/min(range 30-97). According to IDMC criteria, 27.5 % of pts were good prognosis, 60% intermediate and 10.5 % poor. Primary tumor had been removed in 70.5% of pts. Histology was clear cell 89.5%, papillary 4.5%, unclassified 6%. Response rate was 46.5%, stable disease 37.5%, progression 16%. Grade 3-4 toxicities were 4.5% hypertension, 3% mucositis, 1.5% diarrhea and 1.5% anorexia. Dose reduction to 0.89 mg was applied to 15.5% of pts. PFS and OS data will be presented at the Meeting. Conclusions: TIVO showed good activity and favorable safety profile in a real world cohort of unselected pts with metastatic RCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC pts who should receive VEGFR inhibitors in the first line. </jats:p
Prognostic role of body mass index (BMI) in patients with metastatic castration resistant prostate cancer (mCRPC) receiving chemotherapy: Preliminary results from a retrospective Italian multicenter study.
342 Background: Body mass index (BMI) is linked to an increased risk of cancers and a poorer prognosis. However, the evidence on the relationship between high BMI and metastatic castration resistant prostate cancer (mCRPC) is not entirely consistent and the data are conflicting. The aim of this observational, retrospective, multicenter study was to evaluate the correlation between BMI and progression-free survival (PFS) and overall survival (OS) in patients (pts) with mCRPC treated with chemotherapy. Methods: We collected mCRPC pts who received docetaxel 75 mg/m2 every 21 days as first line therapy in6 Italian Cancer Centers from 2005 to 2015. We classified BMI group according with the World Health Organization definition : normal weight BMI < 25kg/m2, overweight 25 ≤ BMI < 30kg/m2, and obese BMI ≥ 30kg/m2. Baseline characteristics and treatment information has been recorded in an anonymized excel file. Results: We collected 113 pts with a median age of 70.7 years (62 to 87) at the time of mCRPC diagnosis. In our cohort 33.6% of pts were normal weight at the HRPC diagnosis, 50.9% were overweight, and 15.5% were obese. At the baseline, 83.3% of obese pts had at least 1 co-morbidity versus 64.9% of normal/overweight pts. Moreover, 27.8% of obese pts needed a docetaxel dose reduction versus 17.5% normal/overweight pts. Only a non-significant trend for the detrimental effect of high BMI on PFS and OS has been documented. Median PFS in obese pts 6.4 months vs 7.0 months in of normal/overweight pts (p = 0.439); median OS in obese pts 38.8 months vs 43.4 months in of normal/overweight pts (p = 0.157). Conclusions: The relationship between BMI and mCRPC is extremely complex and unclear. Even if in this preliminary analysis we failed to confirm a significant association between BMI and survival, the data suggests that obesity may be associated with a lower tolerance to chemotherapy. Overall, we expected to enroll approximately 500 pts and data collection is currently ongoing. </jats:p
Do pathological parameters of primary tumor correlate with overall survival (OS) of metastatic clear-cell renal cell carcinoma (ccRCC)?
549 Background: T and N stage, Fuhrman grade, necrosis and sarcomatoid features in the primary tumor are key prognostic factors for relapse of ccRCC, but they are not part of Heng's algorithm applied to predict OS in the metastatic setting, which instead is based on 6 clinical/laboratory items. Methods: Retrospective analysis on correlation between pathological parameters and OS (from start of first-line targeted therapy) and Heng's prognostic factors in a multicenter cohort of pts with advanced ccRCC, all of whom had undergone surgery on the kidney. Results: From 2006 to 2012, data of 903 eligible metastatic pts were collected from 33 Italian Oncology Institutions, median age 66 years, 72.6% males, 36.4 metastatic at diagnosis. After a median observation of 42 mo, 70,5% of pts died, estimated OS is 28.5 mo. Heng good prognosis pts were 14.45%, intermediate 69.1% and poor 16.45%. Univariate analysis showed that all pathological parameters significantly correlated with OS: T stage 3-4 vs 1-2 (HR 1.3), N1 vs N0 (1.3), Fuhrman grade 3-4 vs 1-2 (1.7) presence of necrosis (1.5) and sarcomatoid features (1,6). All pathological parameters had a strong correlation with a time to metastases < 1 year, while only weak correlations were found with the other clinical prognostic items of Heng's model. At multivariate analysis only N stage showed an independent impact on OS (table). Conclusions: T3-4 stage, N1, Fuhrman grade 3-4, presence of necrosis and sarcomatoid features negatively affect OS of metastatic ccRCC, but clinical items of Heng's model confirm to have a more robust prognostic significance at multivariate analysis. [Table: see text] </jats:p
Progression-free survival (PFS) and overall survival (OS) in patients receiving three targeted therapies (TTs) for metastatic renal cell carcinoma (mRCC)
431 Background: In recent years, TTs have improved the prognosis of mRCC patients (pts). Despite a non-negligible number of pts received 3 TTs in clinical practice, no TTs have been evaluated as third-line. Aim of this study is to investigate the clinical outcome in pts who received 3 TTs. Methods: Pts with clear-cell mRCC who received 3 TTs were included. A questionnaire was sent to main Italian centers involved in the treatment of mRCC. Demographic data, history of RCC, type and length of first-, second- and third-line were collected; MSKCC risk class was calculated before starting the first-line. Sequences were evaluated by class (TKI-TKI-mTOR vs. TKI-mTOR-TKI) or by drug (Su-So-Ev vs. Su-Ev-So). Median PFS, OS and Time to Strategy Failure (TTSF: from start of first- to end of thrid-line) were estimated with the Kaplan-Meyer method with 95% CI and curves were compared with log-rank test. Cox model was used to explore predictors of TTSF and OS. The study had the ethical approval. Results: 2,065 pts were screened and 281 pts (13%) were treated with 3 TTs. No differences were found between TKI-TKI-mTOR and TKI-mTOR-TKI groups. The TTSF was 36.5 (30.5–42.6) mos vs. 29.3 (23.6–34.9) mos (p=0.059), and the OS was 50.7 (40.6–60.8) vs. 37.8 (34.2–41.5) mos (p=0.004), for TKI-TKI-mTOR and and TKI-mTOR-TKI, respectively. TTSF for Su-So-Ev was 32.1 vs. 30.4 mos for Su-Ev-So (p=0.006). The median OS was not reached in the group treated with Su-So-Ev compared to 35.6 (95%CI, 31.6–39.6) mos in the group treated with Su-Ev-So (p<0.001). The univariate and multivariable Cox analyses for TTSF and OS showed that the only predictive factor is the primary resistance to 1st line (HR: 3.15, 95%CI, 1.98-4.99; p<0.001). The Prognostic factors are the initial MSKCC group (HR: 2.07, 95% CI, 1.41 -3.05; p<0.001), the sequence of therapy (HR: 2.59, 95% CI, 1.59-4.22; p<0.001) and the primary resistance to first line (HR: 2.20, 95% CI, 1.16-4.11; p<0.001). Conclusions: We report as the sequential treatment with two antiangiogenic inhibitors followed by an mTOR inhibitor could increase survival and the control disease in metastatic renal cell carcinoma. </jats:p
Progression-free survival (PFS) and overall survival (OS) in patients receiving three targeted therapies (TTs) for metastatic renal cell carcinoma (mRCC).
Safety and clinical outcome of a cohort of patients (pts) with castration resistant prostate cancer (CRPC) treated with abiraterone acetate (AA) in a named patient program (NPP): Updated results of a retrospective study from an Italian cooperative group.
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