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Background: The non-inferiority of dexamethasone (DEX) on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA (netupitant/palonosetron), compared with the guideline-consistent use of DEX was demonstrated in cisplatin. Here, we complete the analysis by assessing the impact of emesis on daily lives of patients receiving DEX-sparing regimens using the Functional Living Index-Emesis (FLIE)., Methods: Chemotherapy-naïve patients undergoing cisplatin (≥70 mg/m 2 ), were given NEPA and DEX (12 mg) on day 1 and randomized to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2-3 (DEX3), or 3) DEX (4 mg twice daily) on days 2-4 (DEX4; control). Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included the FLIE nausea domain, vomiting domain, and overall combined domain scores, as well as the proportion of patients with no impact on daily life (NIDL; overall score > 108). This was a protocol-planned analysis., Results: In the DEX1 group, no significant differences were observed in the FLIE nausea score (48.9 [±1.8; SE] vs. 53.7 [±1.5]), vomiting score (56.6 [±1.4] vs. 58.7 [±0.8]) and overall score (105.6 [±2.8] vs.112.4 [±1.9]) versus DEX4 control; similar results were observed in the DEX3 group for nausea score (49.6 [±1.7]), vomiting score (58.2 [±1]) and overall score (107.8 [±2.4]) versus control. There were no significant between-group differences in the proportion of patients reporting NIDL., Conclusion: Reducing DEX, when administered with NEPA, does not seem to adversely impact the daily functioning in patients undergoing cisplatin., Trial Registration: ClinicalTrials.gov NCT04201769 . Registration date: 17/12/2019 - Retrospectively registered., (© 2022. The Author(s).)

Background: NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle., Methods: In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined., Results: Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65-0.50 for no CINV events on cycles 3 and 4)., Conclusion: The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle., Trial Registration: This trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/2019.

Background: Nausea can be particularly prominent during the delayed period. Therefore, we performed a meta-analysis of the available randomised evidence to assess the average effect of palonosetron plus one-day dexamethasone (DEX; also called the DEX-sparing strategy) compared with palonosetron plus 3-day DEX for control of chemotherapy-induced nausea and vomiting (CINV), focusing on delayed nausea., Methods: Eligible studies were identified through MEDLINE, Embase, and CENTRAL. Data on acute and delayed CINV were collected. Efficacy end points were complete response (CR; no vomiting, and no use of rescue medication), complete protection (CP; CR plus no clinically significant nausea), and total control (TC; CR plus no nausea) during the delayed period (days 2-5 after chemotherapy initiation). All randomised studies comparing palonosetron plus single-dose DEX (with or without another active agent) on day 1 followed by either no further DEX or additional DEX doses (both alone or in combination with another active agent) qualified., Results: Of 864 citations screened, 8 studies with 1970 patients were included in the meta-analysis. During the delayed period, the combined odds ratio (OR) for all comparisons was 0.92 (95% confidence interval [CI], 0.76-1.12) for CR, 0.85 (95% CI, 0.71-1.03) for CP, and 0.92 (95% CI, 0.77-1.11) for TC in patients undergoing moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide-containing chemotherapy (AC). The absolute risk difference (RD) computations for all end points in the delayed period did not exceed the threshold of - 4% (range, - 1% to - 4%). The effect was similar in subgroups defined by various study design parameters. The absolute RD computations in the acute period did not exceed the threshold of 1% (range, 0 to 1%). For one-day vs. 3-day DEX, numbers needed to be treated in order for one additional patient to not experience CR, CP and TC over the delayed period were 100, 25 and 50, respectively., Conclusions: This meta-analysis demonstrates that DEX-sparing regimens do not cause any significant loss in protection against not only vomiting but also nausea induced by single-day MEC or AC during the delayed period. These data should lead clinicians to optimise use of prophylactic DEX in clinical practice.

Background: Clostridium difficile (CD) is a leading cause of diarrhoea among hospitalized patients. The objective of this study was to evaluate the rate, the optimal diagnostic work-up, and outcome of CD infections (CDI) in Internal Medicine (IM) wards in Italy., Methods: PRACTICE is an observational prospective study, involving 40 IM Units and evaluating all consecutive patients hospitalized during a 4-month period. CDI were defined in case of diarrhoea when both enzyme immunoassay for GDH, and test for A/B toxin were positive. Patients with CDI were followed-up for recurrences for 4 weeks after the end of therapy., Results: Among the 10,780 patients observed, 103 (0.96 %) showed CDI, at admission or during hospitalization. A positive history for CD, antibiotics in the previous 4 weeks, recent hospitalization, female gender and age were significantly associated with CDI (multivariable analysis). In-hospital mortality was 16.5 % in CD group vs 6.7 % in No-CD group (p < 0.001), whereas median length of hospital stay was 16 (IQR = 13) vs 8 (IQR = 8) days (p < 0.001) among patients with or without CDI, respectively. Rate of CD recurrences was 14.6 %. As a post-hoc evaluation, 23 out of 34 GDH+/Tox- samples were toxin positive, when analysed by molecular method (a real-time PCR assay). The overall CD incidence rate was 5.3/10,000 patient-days., Conclusions: Our results confirm the severity of CDI in medical wards, showing high in-hospital mortality, prolonged hospitalization and frequent short-term recurrences. Further, our survey supports a 2-3 step algorithm for CD diagnosis: EIA for detecting GDH, A and B toxin, followed by a molecular method in case of toxin-negative samples.

Background: At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed., Methods: Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment., Results: 163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306)., Conclusions: FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.