Cefiderocol use for the treatment of infections by carbapenem-resistant Gram-negative bacteria: an Italian multicentre real-life experience.

BACKGROUND: Cefiderocol is a novel siderophore cephalosporin with promising activity against most carbapenem-resistant Gram-negative bacteria (CRGNB). However, extensive postmarketing experiences are lacking. This study aimed to analyse the early experience on cefiderocol postmarketing use at three tertiary care hospitals in Italy. METHODS: We retrospectively included patients with infections caused by CRGNB treated with cefiderocol at three Italian tertiary care hospitals from 1 March 2021 to 30 June 2022. A multivariate Cox model was used to identify predictors of 30 day mortality. A propensity score (PS) analysis with inverse probability weighting (IPW) was also performed to compare the treatment effect of cefiderocol monotherapy (CM) versus combination regimens (CCRs). RESULTS: The cohort included 142 patients (72% male, median age 67 years, with 89 cases of Acinetobacter baumannii infection, 22 cases of Klebsiella pneumoniae, 27 cases of Pseudomonas aeruginosa and 4 of other pathogens). The 30 day all-cause mortality was 37% (52/142). We found no association between bacterial species and mortality. In multivariate analysis, a Charlson Comorbidity Index >3 was an independent predictor of mortality (HR 5.02, 95% CI 2.37-10.66, P < 0.001). In contrast, polymicrobial infection (HR 0.41, 95% CI 0.21-0.82, P < 0.05) was associated with lower mortality. There was no significant difference in mortality between patients receiving CM (n = 70) and those receiving a CCR (n = 72) (33% versus 40%, respectively), even when adjusted for IPW-PS (HR 1.11, 95% CI 0.63-1.96, P = 0.71). CONCLUSIONS: Real-life data confirm that cefiderocol is a promising option against carbapenem-resistant Gram-negative infections, even as monotherapy.

Sclerotherapy with 3% polidocanol foam to treat second-degree haemorrhoidal disease: Three-year follow-up of a multicentre, single arm, IDEAL phase 2b trial.

BACKGROUND: Sclerotherapy with 3% polidocanol foam is becoming increasingly popular for the treatment of symptomatic I-II or III degree haemorrhoidal disease (HD). However, there are no studies that have reported a follow-up of more than 1 year. The purpose of this study was to analyse the long-term outcomes of sclerotherapy with 3% polidocanol foam in the treatment of II-degree HD. METHODS: This was an open label, single-arm, phase 2b trial conducted in 10 tertiary referral centres for HD. A total of 183 patients with II-degree HD, aged between 18 and 75 years with symptomatic HD according to the Goligher classification and unresponsive to medical treatment, were included in the study and underwent sclerotherapy with 3% polidocanol foam. The efficacy was evaluated in terms of bleeding score, haemorrhoidal disease symptom score (HDSS) and short health scale for HD (SHS-HD) score. Successful treatment was defined as the complete absence of bleeding episodes after 7 days (T1) according to the bleeding score. RESULTS: The overall success rate ranged from 95.6% (175/183) at 1 year to 90.2% (165/183) after the final 3 year follow-up. The recurrence rate, based on the primary outcome, ranged from 12% (15/125) to 28% (35/125). The greatest increase in recurrence (15) was recorded between 12 and 18 months of follow-up, then another five between 18 and 24 months. Both the HDSS and the SHS score remained statistically significant (p < 0.001) from a median preoperative value of 11 (10-13) and 18 (15-20) to 0 (0-2) and 4 (0-4), respectively. Symptom-free (HDSS = 0) patients, excluding patients converted to surgery, increased from 55.5% (101/182) at 1 year to 65.1% at 3 years (110/169). There were no intraoperative complications in redo-sclerotherapy nor additional adverse events (AEs) compared to the first 12 months. CONCLUSIONS: Sclerotherapy with 3% polidocanol foam is gradually establishing itself in the treatment of bleeding HD due to its repeatability, safety, convenience in terms of direct and indirect costs with the absence of discomfort for the patient as well as AEs rather than an excellent overall success rate.

Ceftazidime/avibactam and ceftolozane/tazobactam for the treatment of extensively drug-resistant Pseudomonas aeruginosa post-neurosurgical infections: three cases and a review of the literature.

PURPOSE: Post-neurosurgical infection caused by extensively drug resistant Pseudomonas aeruginosa (XDR-PA) are becoming a matter of great concern due to limited therapeutic options. Although not approved for these indications, the new BetaLactam-BetaLactamase Inhibitor combinations (BLBLIs) could represent a valid salvage treatment. We describe one nosocomial meningitis and two cervical osteomyelitis due to an XDR-PA who were treated with ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) and review the literature. METHODS: The first and the third patients developed an osteomyelitis following cervical stabilization surgery due to an XDR-PA. Although the first patient started treatment with a high dose of C/T, resistance to C/T occurred, so therapy was switched to CZA plus aztreonam. The third patient switched to aztreonam plus CZA due to development of acute kidney injury during therapy with colistin. The second patient had an XDR-PA meningitis following the insertion of an external ventricular catheter and he was treated with C/T plus meropenem and amikacin. RESULTS: All three cases reported were successfully conservatively treated thanks to the use of the new BLBLIs with different combinations. Only few experiences demonstrated an equally favorable outcome: one patient treated with C/T plus fosfomycin for otogenic meningitis caused by an XDR-PA and another case of XDR-PA post-surgical meningitis with CZA in combination with colistin. Finally, the combination of CZA plus aztreonam has proven to be effective on XDR-PA only in limited mostly in vitro studies. CONCLUSION: These recently developed antibiotics, C/T and CZA are promising and complementary therapy options against post-neurosurgical hard-to-treat P. aeruginosa infections. Further prospective real-life studies are required to validate these findings in this special setting.

Carboplatin, methotrexate, vinblastine, and epirubicin (M-VECa) as salvage treatment in patients with advanced bladder cancer: a phase II study.

The primary objective of this study was to determine the activity and safety of carboplatin, methotrexate, vinblastine, and epirubicin (the M-VECa regimen) in patients with advanced bladder cancer after failure of at least one chemotherapy line. Treatment consisted of carboplatin 250 mg/m on day 1, methotrexate 30 mg/m on days 1 and 22, vinblastine 3 mg/m on days 2 and 22, and epirubicin 50 mg/m on day 2 every 28 days until disease progression or death. Response rate was the main end-point. Twenty-five patients were enrolled: the median age was 67 years (range 42-83) and there were 14 patients aged at least 70 years (56%). Fourteen patients had previously received vinflunine as a second-line treatment. Complete remission occurred in one patient (4%), partial remission in five patients (20%), and stable disease in eight patients (32%). The overall response rate was 24% [95% confidence interval (CI), 9.3-45.1%] and the overall disease control rate was 56% (95% CI, 34.9-75.5%). The median progression-free survival was 5.1 months (95% CI, 3.9-6.4) and the median overall survival was 9.5 months (95% CI, 7.1-11.2). Treatment was well tolerated: grade 3 neutropenia was documented in five patients and grade 3 nausea and vomiting in two patients. The M-VECa regimen seems to be feasible as second-line or third-line treatment in patients with advanced bladder cancer who have been pretreated with one or more chemotherapy lines, and may achieve encouraging results in terms of disease control rate, progression-free survival, and overall survival.

Tolerability of cabazitaxel in patients with metastatic castration-resistant prostate cancer progressing after docetaxel and abiraterone acetate: a single-institution experience.

Both abiraterone acetate (AA) and cabazitaxel (Cbz) have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or after docetaxel (D). Although no standard sequencing has been established as yet, Cbz has recently been proven to be active after AA. However, to date, few data are available on its safety in this setting. Therefore, the primary endpoint of this study was to investigate Cbz tolerability in mCRPC patients treated previously with D and AA. From April 2011 to the present, 43 mCRPC patients received AA after D at our institution. Of these, 22 patients were subsequently treated with Cbz and were evaluable for toxicity in the present retrospective study. Cbz was administered at a dose of 25 mg/m plus 10 mg oral prednisone every 3 weeks. Adverse events (AEs) were reported using the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. Despite the advanced stage of disease and frailty of our study population, there were no unexpected side effects. The most common AEs were hematologic. Neutropenia was observed in nine (40.9%) patients and of grade≥3 in six (27.2%). No febrile neutropenia occurred. The most common nonhematologic AEs were diarrhea and asthenia, reported in eight (36.3%) and in five (22.7%) patients, respectively. In this setting, Cbz toxicity seems to be manageable and comparable with second-line Cbz. Therefore, our results seem to support the safety of Cbz as a third-line treatment for mCRPC patients.

Maintenance treatment with oral cyclophosphamide and bevacizumab in patients with recurrent epithelial ovarian cancer.

AIM: To evaluate the efficacy and safety of maintenance treatment with oral cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian cancer. PATIENTS & METHODS: Induction treatment consisted of cisplatin, epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance treatment consisted of oral Cy 50 mg, days 1-14 and Bev 15 mg/kg, every 3 weeks until disease progression occurred. RESULTS: In total, 39 patients were enrolled: after induction chemotherapy, the objective response was 74.3%. The median progression-free survival was 13.3 months, and the median overall survival was 33.2 months. Toxicity during maintenance treatment was mild. CONCLUSION: Maintenance with Cy and Bev may achieve encouraging results in terms of progression-free survival and overall survival in recurrent ovarian cancer patients.

Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer.

The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41-0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously.

Early Detection of Disease Progression in Metastatic Cancers: Could CTCs Improve RECIST Criteria?

Early detection of disease progression is a crucial issue in the management of cancer patients, especially in metastatic settings. Currently, treatment selection mostly relies on criteria based on radiologic evaluations (RECIST). The aim of the present retrospective study is to evaluate the potential inclusion of circulating tumor cells (CTCs) in hybrid criteria. CTC counts from a total of 160 patients with different metastatic tumors were analyzed for this purpose. In our cohort, 73 patients were affected by breast cancer, 69 by colorectal cancer and 18 by prostate cancer. PFS and OS were evaluated according to the corresponding prediction of disease progression by CTCs and RECIST criteria. In breast cancer, CTC-I has an important impact on the progression-free survival (PFS) and overall survival (OS) values. When CTC-I predicted earlier than RECIST-I, the disease progression, the PFS and OS were shorter with respect to the opposite case. In particular, PFS was 11 (5-16) vs. 34 (23-45)-with p < 0.001-and OS was 80 (22-138) vs. 116 (43-189), p = 0.33. The results suggest a promising role of CTCs as complementary information which could significantly improve the clinical outcomes, and they encourage consideration of future trials to evaluate new hybrid criteria, particularly for patients with breast cancer.

Nutritional counselling and risk factors for obesity: an observational study in toddlers.

BACKGROUND: Nutrition exerts a fundamental role in the prevention of obesity (OB). The aim of this study was to assess the extent to which well recognized risk factors for early OB can be associated to overweight (OW) or OB under a standardized nutritional approach and surveillance in toddlers. METHODS: The eligible population was represented by 676 toddlers aged 24-36 months, assigned to 18 primary care pediatricians trained on nutritional issues who shared a standardized nutritional approach. Six-hundred-twenty-nine children (333 boys), mean age 27.8 ± 4.2 months were effectively included in this observational study. Parents received nutritional advice with particular emphasis to proteins and sugar composition supported by leaflets and reinforced at each visit. Body mass index was assessed at the age of 24-36 months. The following individual and family risk factors were considered: gestational age, birth weight, eutocic/caesarean delivery, milk feeding history, household smoking or antibiotics exposure, parents' weight, height and educational level. Prevalence of OW/OB was compared to a group of 742 toddlers (373 boys) under usual care. RESULTS: Under a standardized nutritional counselling, 28.1% toddlers were classified as OW/OB compared to 36.9% toddlers under usual care (p = 0.005). In unadjusted models, parental OW/OB was significantly associated to OW/OB in toddlers (p < 0.01), while high birth weight did not reach statistical significance (p = 0.07). In adjusted models, including all the explanatory variables studied, only paternal OW/OB vs. normal weight was significantly associated to OW/OB in toddlers (OR 2.035, 95% confidence interval 1.206-3.436). No protective effect of exclusive breast feeding during the first 6 months of age was demonstrated. CONCLUSIONS: Toddlers under a standardized nutrition counselling focused to limit protein and simple sugars, showed lower prevalence of OW/OB compared to usual care. Healthy promotion activities should take into account the influence of paternal BMI on the offspring adiposity.

Lenvatinib Versus Sorafenib in Advanced Hepatic Cell Carcinoma: A Double Center Retrospective Analysis.

BACKGROUND/AIM: We conducted a retrospective analysis in our center (Umberto I Polyclinic) in collaboration with Campus Biomedico Polyclinic to assess the results of the REFLECT study, which was the first study that demonstrated the non-inferiority of Lenvatinib to Sorafenib. PATIENTS AND METHODS: We identified 21 patients affected by advanced hepatocellular carcinoma during the last 3 years who were treated in our centers. They were subdivided according to the treatment administered (Lenvatinib or Sorafenib). Progression-free survival (PFS) and overall survival (OS) were calculated, and subgroups were compared using the log-rank test. Specific predictive and prognostic factors were identified. The safety profile of the two drugs and the collateral effects were evaluated. RESULTS: The OS in patients in the Lenvatinib arm was 19 (months and 12.5 months in the Sorafenib arm. PFS in patients in the Lenvatinib arm was 6 months and 2.5 months in the Sorafenib arm. OS and PFS in patients treated with Lenvatinib were higher in any subcategory analyzed whereas no positive predictors of response to Sorafenib were found. Based on data from literature, the albumin bilirubin index (ALBI) grade was found to be a key prognostic factor. Patients treated with Sorafenib had more adverse events than those treated with Lenvatinib (100% versus 81.8%, respectively). Patients treated with Sorafenib had more frequently hand-foot syndromes, diarrhea, and nausea whereas patients treated with Lenvatinib commonly had hypertension, proteinuria, and weight loss. CONCLUSION: Lenvatinib was found to be better than Sorafenib in terms of both survival and toxicity, in advanced hepatic cell carcinoma patients.

Obesity as a Risk Factor of Severe Outcome of COVID-19: A Pair-Matched 1:2 Case-Control Study.

BACKGROUND AND AIM: The nature of the association between obesity and poor prognosis of COVID-19 without the evaluation of other co-pathologies associated has not yet been clearly evaluated. The aim of the present pair-matched case-control study was to investigate the outcome of patients with SARS-CoV-2 infection in obese and non-obese patients matched considering gender, age, number of comorbidities, and Charlson Comorbidity Index. METHODS: All the adults hospitalized for SARS-CoV-2 infection and with BMI ≥ 30 kg/m2 were included (Cases). For each Case, two patients with BMI < 30 kg/m2 pair matched for gender, age (±5 years), number of comorbidities (excluding obesity), and Charlson Comorbidity Index (±1) were enrolled (Controls). RESULTS: Of the 1282 patients with SARS-CoV-2 infection followed during the study period, 141 patients with obesity and 282 patients without were enrolled in the case and control groups, respectively. Considering matching variables, there was no statistical difference between the two groups. Patients in the Control group developed more frequently a mild-moderate disease (67% vs. 46.1%, respectively), whereas obese patients were more prone to need intensive care treatment (41.8% vs. 26.6%, respectively; p = 0.001). Moreover, the prevalence of death during hospitalization was higher in the Case group than in the Control group (12.1% vs. 6.4%, p = 0.046). DISCUSSION: We confirmed an association between obesity and severe outcome of patients with COVID-19, also considering other factors associated with a severe outcome of COVID-19. Thus, in the case of SARS-CoV-2 infection, the subjects with BMI ≥ 30 kg/m2 should be evaluated for early antiviral treatment to avoid the development of a severe course.

Superinfections caused by carbapenem-resistant Enterobacterales in hospitalized patients with COVID-19: a multicentre observational study from Italy (CREVID Study).

Objectives: To describe clinical characteristics and outcomes of COVID-19 patients who developed secondary infections due to carbapenem-resistant Enterobacterales (CRE). Methods: Retrospective observational study including COVID-19 patients admitted to 12 Italian hospitals from March to December 2020 who developed a superinfection by CRE. Superinfection was defined as the occurrence of documented bacterial infection >48 h from admission. Patients with polymicrobial infections were excluded. Demographic, clinical characteristics and outcome were collected. Isolates were classified as KPC, metallo-ß-lactamase (MBL) and OXA-48-producing CRE. A Cox regression analysis was performed to identify factors independently associated with 30 day mortality. Results: Overall, 123 patients (median age 66 years, IQR 59-75) were included. The majority of infections occurred in the ICU (81, 65.9%), while 42 (34.1%) in medical wards. The most common types of infection were bloodstream infections (BSI) (n = 64, 52%), followed by urinary-tract infections (UTI) (n = 28, 22.8%), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) (n = 28, 22.8%), intra-abdominal infections (n = 2, 1.6%) and skin infections (n = 1, 0.8%). Sixty-three (51.2%) infections were caused by KPC-, 54 (43.9%) by MBL-, and 6 (4.8%) by OXA-48-producing CRE. Thirty-day mortality was 33.3% (41/123). On Cox regression analysis, HAP/VAP compared with UTI (HR 7.23, 95% CI 2.09-24.97, P = 0.004), BSI compared with UTI (HR 3.96, 95% CI, 1.33-11.77, P = 0.004), lymphopenia on admission (HR 3, 95% CI 1.44-6.26, P = 0.003) and age (HR 1.05, 95% CI 1.02-1.08, P = 0.002) were predictors of 30 day mortality. Conclusions: Superinfections by CRE were associated with high risk of 30 day mortality in patients with COVID-19. HAP/VAP was the strongest predictor of death in these patients.

Combined Resistance to Ceftolozane-Tazobactam and Ceftazidime-Avibactam in Extensively Drug-Resistant (XDR) and Multidrug-Resistant (MDR) Pseudomonas aeruginosa: Resistance Predictors and Impact on Clinical Outcomes Besides Implications for Antimicrobial Stewardship Programs.

A retrospective case-control study was conducted at Modena University Hospital from December 2017 to January 2019 to identify risk factors and predictors of MDR/XDR Pseudomonas aeruginosa (PA) isolation with resistance to ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T), and of mortality among patients infected/colonized. Among 111 PA isolates from clinical/surveillance samples, 60 (54.1%) were susceptible to both drugs (S-CZA-C/T), while 27 (24.3%) were resistant to both (R-CZA-C/T). Compared to patients colonized/infected with S-CZA-C/T, those with R-C/T + CZA PA had a statistically significantly higher Charlson comorbidity score, greater rate of previous PA colonization, longer time before PA isolation, more frequent presence of CVC, higher exposure to C/T and cephalosporins, longer hospital stay, and higher overall and attributable mortality. In the multivariable analysis, age, prior PA colonization, longer time from admission to PA isolation, diagnosis of urinary tract infection, and exposure to carbapenems were associated with the isolation of a R-C/T + CZA PA strain, while PA-related BSI, a comorbidity score > 7, and ICU stay were significantly associated with attributable mortality. C/T and CZA are important therapeutic resources for hard-to-treat PA-related infections, thus specific antimicrobial stewardship interventions should be prompted in order to avoid the development of this combined resistance, which would jeopardize the chance to treat these infections.

Selective parallel integration of individual metallic single-walled carbon nanotubes from heterogeneous solutions.

The dielectrophoretic separation of individual metallic single-walled carbon nanotubes (SWNTs) from heterogeneous solutions and their simultaneous deposition between electrodes is achieved and confirmed by direct electric transport measurements. Out-of-solution guided parallel assembly of individual SWNTs was investigated for electric field frequencies between 1 and 200 MHz. At 200 MHz, 19 of the 22 deposited SWNTs (86%) displayed metallic behavior, whereas at lower frequencies the expected random growth distribution of 1/3 metallic SWNTs prevailed. A threshold separation frequency of 188 MHz is extracted from a surface-conductivity model, and a conductivity weighting factor is introduced to elucidate the separation frequency dependence. Low-frequency experiments and numerical simulations show that long-range nanotube transport is governed by hydrodynamic effects whereas local trapping is dominated by dielectrophoretic forces. The electrokinetic framework of dielectrophoresis in low-concentration solutions is thus provided and allows a deeper understanding of the underlying mechanisms in dielectrophoretic deposition processes for long and large-diameter SWNT-based low-resistance device integration.

Forecasting Energy Consumption in the EU Residential Sector.

The present paper aims to introduce a top down methodology for the forecasting of residential energy demand in four European countries, namely Germany, Italy, Spain, and Lithuania. The methodology employed to develop the estimation is based on econometric techniques. In particular, a logarithmic dynamic linear constant relationship of the consumption is proposed. Demand is estimated as a function of a set of explaining variables, namely heating degree days and gross domestic product per capita. The results confirm that the methodology can be applied to the case of Germany, Italy, and Spain, whereas it is not suitable for Lithuania. The analysis of elasticities of the demand with respect to the gross domestic product per capita shows a negative value for Germany, -0.629, and positive values for Italy, 0.837, and Spain, 0.249. The forecasting of consumption shows that Germany and Italy are more sensitive to weather conditions with respect to Spain and an increase in the demand of 8% and 9% is expected in case of cold climatic conditions.

Measles in pregnant women: A systematic review of clinical outcomes and a meta-analysis of antibodies seroprevalence.

OBJECTIVES: Pregnant women represent a category at high risk of severe measles infection, that negatively affects the fetus as well. A systematic review of clinical outcomes of measles infection in gravid subjects and a meta-analysis of antibodies prevalence among pregnant women was conducted. METHODS: MEDLINE and EMBASE databases were searched up to 18 June 2018. The screening focused on: (i) articles describing the outcome of measles in pregnancy, synthesized in a descriptive fashion; (ii) articles addressing the measles seroprevalence in cohorts of gravid women, analysed quantitatively. RESULTS: Twenty-nine articles met inclusion criteria. A total of 420 cases of measles in gravid subjects were described, from 1941 to 2012. Among women, 18 deaths (4.3%) occurred, and the most frequent complication was pneumonia (75/420, 17.9%). Prematurity was the most important complication concerning fetal outcomes (55 out of 410 cases with available data, 13.4%). The random-effects pooled seroprevalence of measles in 20,546 gravid women worldwide was 89.3% (95% CI: 87.3-91.1%), that decreased, although not in a statistically significant way, over time (p = 0.54). CONCLUSIONS: Measles infection in pregnancy is dangerous both for the mother and the foetus. Antibody seroprevalence among gravid women on a global scale is lower than the herd immunity threshold.

Prexasertib, a checkpoint kinase inhibitor: from preclinical data to clinical development.

Checkpoint kinases 1 and 2 (CHK1 and CHK2) are important multifunctional proteins of the kinase family. Their main function is to regulate DNA replication and DNA damage response. If a cell is exposed to exogenous damage to its DNA, CHK1/CHK2 stops the cell cycle to give time to the cellular mechanisms to repair DNA breakage and apoptosis too, if the damage is not repairable to activate programmed cell death. CHK1/CHK2 plays a crucial role in the repair of recombination-mediated double-stranded DNA breaks. The other important functions performed by these proteins are the beginning of DNA replication, the stabilization of replication forks, the resolution of replication stress and the coordination of mitosis, even in the absence of exogenous DNA damage. Prexasertib (LY2606368) is a small ATP-competitive selective inhibitor of CHK1 and CHK2. In preclinical studies, prexasertib in monotherapy has shown to induce DNA damage and tumor cells apoptosis. The preclinical data and early clinical studies advocate the use of prexasertib in solid tumors both in monotherapy and in combination with other drugs (antimetabolites, PARP inhibitors and platinum-based chemotherapy). The safety and the efficacy of combination therapies with prexasertib need to be better evaluated in ongoing clinical trials.