Use of clofarabine for acute childhood leukemia.

A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity in acute lymphoblastic leukemia as well as in myeloid disorders. As the only new antileukemic chemotherapeutic agent to enter clinical use in the last 10 years, clofarabine was approved as an orphan drug with the primary indication of use in pediatric patients. Toxicity has been tolerable in a heavily pretreated patient population, and clofarabine has been demonstrated to be safe, both as a single agent and in combination therapies. Liver dysfunction has been the most frequently observed adverse event, but this is generally reversible. Numerous Phase I and II trials have recently been conducted, and are still ongoing in an effort to find the optimal role for clofarabine in various treatment strategies. Concomitant use of clofarabine, cytarabine, and etoposide was confirmed to be safe and effective in two independent trials. Based on the promising results when used as a salvage regimen, clofarabine is now being investigated for its potential to become part of frontline protocols

Use of clofarabine for acute childhood leukemia

A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity in acute lymphoblastic leukemia as well as in myeloid disorders. As the only new antileukemic chemotherapeutic agent to enter clinical use in the last 10 years, clofarabine was approved as an orphan drug with the primary indication of use in pediatric patients. Toxicity has been tolerable in a heavily pretreated patient population, and clofarabine has been demonstrated to be safe, both as a single agent and in combination therapies. Liver dysfunction has been the most frequently observed adverse event, but this is generally reversible. Numerous Phase I and II trials have recently been conducted, and are still ongoing in an effort to find the optimal role for clofarabine in various treatment strategies. Concomitant use of clofarabine, cytarabine, and etoposide was confirmed to be safe and effective in two independent trials. Based on the promising results when used as a salvage regimen, clofarabine is now being investigated for its potential to become part of frontline protocols

Wellbeing in Workers during COVID-19 Pandemic: The Mediating Role of Self-Compassion in the Relationship between Personal Resources and Exhaustion

Italy was the second country to be affected by COVID-19 in early 2020, after China. The confrontation with the pandemic led to great changes in the world of work and, consequently, to the personal world of workers. In such a challenging situation, it is essential to be able to rely on resources that facilitate individual coping. The aim of this study was to understand the association between personal resources (optimism and humor) and exhaustion, and the role of self-compassion in this relationship. A structural equation model (SEM) was used to test the hypotheses on a heterogeneous sample of 422 Italian workers during the first lockdown in April–May 2020. The results revealed that optimism and humor were positively associated with self-compassion; optimism and humor also had a negative association with exhaustion; and self-compassion had a mediating role between the two personal resources and exhaustion. These results confirmed the importance of personal resources in maintaining workers’ wellbeing during a challenging period such as the pan-demic. The present study also contributes to the body of knowledge on self-compassion, a relatively new construct that has been little studied in the organizational field

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.<p></p> Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.<p></p> Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.<p></p> Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings

Physiological protection of probiotic microcapsules by coatings

Nowadays, food and nutrition have a greater impact in people's concerns, with the awareness that nutrition have a direct impact in health and wellbeing. Probiotics have an important role in this topic and consumers are starting to really understand their potential in health, leading to an increasing interest of the companies to their commercial use in foods. However, there are several limitations to the use of probiotics in foods and beverages, being one of them their efficiency (directly associated to their survival rate) upon ingestion. This work is focused in microencapsulation techniques that have been used to increase probiotics efficiency. More specifically, this work reviews the most recent and relevant research about the production and coating techniques of probiotic-loaded microcapsules, providing an insight in the effect of these coatings in probiotics survival during the gastrointestinal phase. This review shows that coatings with the better performances in probiotics protection, against the harsh conditions of digestion, are chitosan, alginate, poly-L-lysine and whey protein. Chitosan presented an interesting performance in probiotics protection being able to maintain the initial concentration of viable probiotics during a digestive test. The analyses of different works also showed that the utilization of several coatings does not guarantee a better protection in comparison with monocoated microcapsules.The author Philippe E. Ramos is recipient of fellowships from the Fundação para a Ciência e Tecnologia, POPH-QREN and FSE (FCT, Portugal) through the grant SFRH/BD/80800/2012. This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). RECI Project (Until December of 2017): This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the Project RECI/BBBEBI/0179/2012 (FCOMP-01-0124-FEDER-027462).info:eu-repo/semantics/publishedVersio

Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases

BACKGROUND: In breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel. METHODS: In 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, ≥ 11 and ≥ 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels. RESULTS: Distant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off ≥ 11 U/mL, MCA showed the lowest specificity (42%); with cut-off ≥ 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With ≥ 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With ≥ 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel. CONCLUSION: At both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients

Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer

The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg m−2) was given every 2 weeks and PVI 5-FU (300 mg m−2day−1) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15–46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n= 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3–4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7–73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer. © 2001 Cancer Research Campaig

Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study)

BACKGROUND: The conventional treatment options for advanced gastric patients remain unsatisfactory in terms of response rate, response duration, toxicity, and overall survival benefit. The purpose of this phase II study was to evaluate the activity and safety of cetuximab combined with cisplatin and docetaxel as a first-line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma. METHODS: Untreated patients with histologically confirmed advanced gastric or gastro-oesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg m(-2) i.v. followed by weekly doses of 250 mg m(-2), cisplatin 75 mg m(-2) i.v. on day 1, docetaxel 75 mg m(-2) i.v. on day 1, every 3 weeks, for a maximum of 6 cycles, and then cetuximab maintenance treatment was allowed in patients with a complete response, partial response, or stable disease. RESULTS: Seventy-two patients (stomach 81.9% and gastro-oesophageal junction 18.1%; locally advanced disease 4.2%; and metastatic disease 95.8%) were enrolled. The ORR was 41.2% (95% CI, 29.5-52.9). Median time to progression was 5 months (95% CI, 3.7-5.4). Median survival time was 9 months (95% CI, 7-11). The most frequent grades 3-4 toxicity was neutropenia (44.4%). No toxic death was observed. CONCLUSIONS: The addition of cetuximab to the cisplatin/docetaxel regimen improved the ORR of the cisplatin/docetaxel doublet in the first-line treatment of advanced gastric and gastro-oesophageal junction adenocarcinoma, but this combination did not improve the TTP and OS. The toxicity of cisplatin/docetaxel chemotherapy was not affected by the addition of cetuximab

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB/IV and WHO performance status 0–2 were eligible. No upper age limit was defined. Patients received vinorelbine 25 mg m−2 or gemcitabine 1000 mg m−2 on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles. HRQOL questionnaires were completed at baseline, before chemotherapy and every 8 weeks until 49 weeks. During 14 months, 432 patients were included (VC, n=218; GC, n=214). Median survival was 7.3 vs 6.4 months, 1-year survival 28 vs 30% and 2-year survival 7 vs 7% in the VC and GC arm, respectively (P=0.89). HRQOL, represented by global QOL, nausea/vomiting, dyspnoea and pain, showed no significant differences. More grade 3–4 anaemia (P<0.01), thrombocytopenia (P<0.01) and transfusions of blood (P<0.01) or platelets (P<0.01) were observed in the GC arm. There was more grade 3–4 leucopoenia (P<0.01) in the VC arm, but the rate of neutropenic infections was the same (P=0.87). In conclusion, overall survival and HRQOL are similar, while grade 3–4 toxicity requiring interventions are less frequent when VC is compared to GC in advanced NSCLC