NK Cell-Based Immunotherapy in Colorectal Cancer.

Human Natural Killer (NK) cells are all round players in immunity thanks to their powerful and immediate response against transformed cells and the ability to modulate the subsequent adaptive immune response. The potential of immunotherapies based on NK cell involvement has been initially revealed in the hematological setting but has inspired the design of different immune tools to also be applied against solid tumors, including colorectal cancer (CRC). Indeed, despite cancer prevention screening plans, surgery, and chemotherapy strategies, CRC is one of the most widespread cancers and with the highest mortality rate. Therefore, further efficient and complementary immune-based therapies are in urgent need. In this review, we gathered the most recent advances in NK cell-based immunotherapies aimed at fighting CRC, in particular, the use of monoclonal antibodies targeting tumor-associated antigens (TAAs), immune checkpoint blockade, and adoptive NK cell therapy, including NK cells modified with chimeric antigen receptor (CAR-NK).

Case report: Variable response to immunotherapy in ovarian cancer: Our experience within the current state of the art.

Despite recent advances in ovarian cancer (OC) treatment, including the introduction of bevacizumab and PARP-inhibitors, OC remains a lethal disease. Other therapeutic options are being explored, such as immunotherapy (IT), which has been proved effective in many solid tumors. Findings about tumor-infiltrating cytotoxic and regulatory T cells, together with the expression of PD-1 on immune cells and of PD-L1 on tumor cells, gave the rationale for an attempt to the use of IT also in OC. We treated two patients with avelumab, an anti-PD-L1 monoclonal antibody, after the first line of chemotherapy: Patient A underwent 19 cycles of maintenance therapy with avelumab with a disease-free interval of 12 months, whereas patient B showed a slight progression of disease after only eight cycles. A higher PD-L1 expression in tumor cells of patient A was detected. She also underwent a genomic assessment that described the presence of a high Tumor Mutational Burden (TMB) and a status of Loss of Heterozygosity (LoH). This different response to the same treatment puts in evidence that some genomic and immune features might be investigated.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment.

PURPOSE: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment. PATIENTS AND METHODS: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose. RESULTS: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009). CONCLUSION: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS. GOV IDENTIFIER: NCT04932863.

Home Se-Cure: A Home Care Service for Cancer Patients during the COVID-19 Pandemic.

Cancer patients are exposed to a greater risk of COVID-19 infection, resulting in treatment delays and unnecessary hospitalizations. International authorities have suggested reducing visits to hospitals and guarantee continuity of care. We developed a home care project called Home Se-Cure (HSC) to guarantee the continuity of oral, intramuscular, and subcutaneous cancer therapy during COVID-19. The Home Se-Cure project included cancer patients living near Galliera Hospital. Patients received home visits by registered nurses (RNs), whoperformed blood tests and delivered cancer therapies. Patients were instructed to take drugs after blood test results and therapy confirmation by oncologists. Sixty-six patients decided to participate and 38 declined the service. A customer satisfaction questionnaire was administered to a subgroup of patients participating in the project. The most prevalent disease in the HSC group was prostate cancer. The mean age of the patients in HSC was 78.4 years and 68.9 in the decliner group. The majority of the HSC participants appreciated the project because they could stay at home (71%) and reduce the risk of COVID-19 contagion (67.7%). Compared to decliners, the time the study group saved was 2033 hours. HSC guaranteed the continuity of care during the COVID-19 pandemic by reducing the number of patients in the hospital and avoiding crowds in the waiting room.

Patient- versus physician-reported outcomes in a low-dose tamoxifen trial in noninvasive breast cancer.

BACKGROUND: We recently conducted a de-escalation trial of low-dose tamoxifen 5 mg/day ("babytam", BT) or placebo given for 3 years in 500 women with noninvasive breast cancer. Women on babytam had a 52% reduction of recurrence (invasive breast cancer or DCIS) after 5 years. Since menopausal symptoms are major reasons for treatment withdrawal during tamoxifen preventive therapy, we compared and analyzed the patient-reported outcomes (PROs) with the physician-reported adverse events and studied their association with recurrence. METHODS: Menopausal symptoms recorded by physicians using the Common Terminology Criteria (CTCAEs) were compared with a patient self-reported validated questionnaire reviewed by a research nurse at baseline and every 6 months up to 36 months. Hot flashes (HF), the main outcome measure, were detected through a self-report 7-day diary for frequency and intensity. Treatment adherence and efficacy were assessed by the Kaplan-Meier curves and the Cox model. RESULTS: The number of HF events at 12, 24, and 36 months for PROs versus CTCAEs was 246 versus 12, 238 versus 8, and 210 versus 4, respectively. The majority of events were grade 1. There was no difference in PROs between babytam and placebo except for HF daily frequency, which increased by 1.5 events (95% CI, 1.1-1.8) on placebo to 2.1 on babytam (95% CI, 1.7-2.5, p = 0.05). The presence of HF at baseline was a favorable prognostic factor for recurrence and a predictive factor for response to babytam. Adherence was similar between babytam and placebo. CONCLUSIONS: The use of PROs is effective for identifying frequent mild grade menopausal symptoms which are underestimated by physicians but important prognostic and predictive factors. Research nurse can use these results as a tool to reassure patients about symptoms, improve adherence to treatment, and limit dropouts.

To Enhance or Not to Enhance? The Role of Contrast Medium 18F-FDG PET/CT in Recurrent Ovarian Carcinomas.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET/CT) represents the mainstay diagnostic procedure for suspected ovarian cancer (OC) recurrence. PET/CT can be integrated with contrast medium and in various diagnostic settings; however, the effective benefit of this procedure is still debated. We aimed to compare the diagnostic capabilities of low-dose and contrast-enhanced PET/CT (PET/ldCT and PET/ceCT) in patients with suspected ovarian cancer relapse. Materials and Methods: 122 OC patients underwent both PET/ldCT and PET/ceCT. Two groups of nuclear medicine physicians and radiologists scored the findings as positive or negative. Clinical/radiological follow-up was used as ground truth. Sensitivity, specificity, negative/positive predictive value, and accuracy were calculated at the patient and the lesion level. Results: A total of 455 and 474 lesions were identified at PET/ldCT and PET/ceCT, respectively. At the lesion level, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were not significantly different between PET/ldCT and PET/ceCT (98%, 93.3%, 97.4%, 94.9%, and 96.9% for PET/ldCT; 99%, 95.5%, 98.3%, 97%, and 98% for PET/ceCT, p = ns). At the patient level, no significant differences in these parameters were identified (e.g., p = 0.22 and p = 0.35 for accuracy, in the peritoneum and lymph nodes, respectively). Smaller peritoneal/lymph node lesions close to physiological FDG uptake sources were found in the cases of misidentification by PET/ldCT. PET/ceCT prompted a change in clinical management in four cases (3.2%) compared to PET/ldCT. Conclusions: PET/ceCT does not perform better than PET/ldCT but can occasionally clarify doubtful peritoneal findings on PET/ldCT. To avoid unnecessary dose to the patient, PET/ceCT should be excluded in selected cases.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment. Role of the Research Nurse.

BACKGROUND: Vaccines have shown 95% protection from COVID-19 disease in healthy populations. Initial findings in cancer patients suggest a lower seroconversion and greater toxicity possibly related to myelo-immunosuppressive therapies. AIM: We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunization (AEFI) to the BNT162b2 vaccine in cancer patients on active treatment. METHODS: Blood samples were collected by the research nurse at first dose (visit 1), second dose (visit 2), after 42 days (visit 3) and after 6 months (visit 4). At visit 1, 3 and 4 participants received: Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer. Patients who ended treatment >6 months on active surveillance served as controls. RESULTS: Between March and July 2021, 320 subjects were recruited and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immunotherapy. Compared to controls, the risk of no IgG response was greater for chemotherapy (P=0.033), targeted therapy (0.005) and hormonotherapy (P=0.051). Lymphocyte count less than 1x109/L, older age and advanced stage also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (P=0.001) and younger patients (P=0.009). CONCLUSIONS: A third booster dose and long-term serological testing is required in subjects who have not responded to the vaccine. NURSING IMPLICATIONS: nurses must take responsibility for promoting and protecting the health of cancer patients.

Aromatase Inhibitors as Adjuvant Treatment for ER/PgR Positive Stage I Endometrial Carcinoma: A Retrospective Cohort Study.

OBJECTIVE: Although endometrial cancer (EC) is a hormone dependent neoplasm, there are no recommendations for the determination of steroid hormone receptors in the tumor tissue and no hormone therapy has ever been assessed in the adjuvant setting. The purpose of this study was to explore the effect of adjuvant aromatase inhibitors (AIs) on progression-free survival (PFS) and overall survival (OS) in patients with early stage and steroid receptors-positive EC. METHODS: We retrospectively analyzed clinical and pathological factors in 73 patients with high-risk (49.3%) or low-risk (50.7%) stage I (n = 71) or II (n = 2) endometrial cancer who received by their preference after counseling either no treatment (reference group) or AI. Prognostic factors were well balanced between groups. Expression of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 index was correlated with clinical outcomes. RESULTS: Univariate and multivariate Cox proportional regression analyses, adjusted for age, grade, stage, depth of myometrial invasion, lymphovascular space invasion, BMI, ER, PgR and Ki-67 labeling index levels, showed that PFS and OS had a trend to be longer in patients receiving AI than in the reference group HR= 0.23 (95% CI; 0.04-1.27) for PFS and HR= 0.11 (95% CI; 0.01-1.36) for OS. CONCLUSION: Compared with no treatment, AI exhibited a trend toward a benefit on PFS and OS in patients with early stage hormone receptor-positive EC. Given the exploratory nature of our study, randomized clinical trials for ER/PgR positive EC patients are warranted to assess the clinical benefit of AI and the potential predictive role of steroid receptors and Ki-67.

Estimating the magnitude of clinical benefit of systemic therapy in patients with DCIS or pre-invasive disease of the breast.

The challenge of effective management of ductal carcinoma in situ (DCIS) and other pre-malignant disorders of the breast is to select patients who will not progress to invasive carcinoma from those at the highest risk who require radiotherapy and/or endocrine therapy to minimize the risk of a subsequent invasive recurrence. Although IBIS-II and NSABP-B35 DCIS phase III trials proved that tamoxifen 20 mg/day and anastrozole reduce the risk of ipsilateral and contralateral events, the toxicities of both drugs have hampered the drug uptake by high-risk women. We recently reported results of a 3-year placebo-controlled trial of low-dose (5 mg/d) tamoxifen in 500 women with intraepithelial neoplasia (70% DCIS). At a median follow-up of 5 years, women randomly assigned to low-dose tamoxifen had half the number of subsequent diagnoses of DCIS or invasive cancer compared with those randomly assigned to placebo but no increase in thromboembolic events or endometrial cancers. The 5-year number needed to treat was 22 (95% CI, 20-27). Our attention is now focused on prognostic and predictive markers to identify patients who can derive the greatest benefits from low dose tamoxifen, such as for instance the expression of 23 genes involved in cell cycle progression (CCP). In conclusion, we endorse an active treatment of DCIS as the standard of care.

Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Precision Medicine is becoming the new paradigm in healthcare as it enables better resources allocation, treatment optimization with a potential side-effects reduction and consequent impact on quality of life and survival. This revolution is being catalyzed by liquid biopsy technologies, which provide prognostic and predictive information for advanced cancer patients, without the analytical and procedural drawbacks of tissue-biopsy. In particular, circulating tumor DNA (ctDNA) is gaining momentum as a clinically feasible option capable to capture both spatial and temporal tumor heterogeneity. Several techniques are currently available for ctDNA extraction and analysis, each with its preferential case scenarios and preanalytical implications which must be taken into consideration to effectively support clinical decision-making and to better highlight its clinical utility. Aim of this review is to summarize both analytical developments and clinical evidences to offer a comprehensive update on the deployment of ctDNA in breast cancer's (BC) characterization and treatment.

Clinical benefit and risk of death with endocrine therapy in ovarian cancer: A comprehensive review and meta-analysis.

BACKGROUND: Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown. METHODS: Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were calculated according with type of drug, ER and PgR status, platinum resistance, line of therapy, tumor grade and tamoxifen dose. RESULTS: Fifty-three trials in 2490 patients were analyzed. Overall, SCBR was 41% (95%CI, 0.34-0.48) for any endocrine treatment, 43% (95%CI, 0.30-0.56) for tamoxifen, 39% (95%CI, 0.29-0.50) for aromatase inhibitors and 37% (95%CI, 0.26-0.48) for progestins. The SCBR for ER+ and/or PgR+ tumors was 46% (95%CI, 0.34-0.57) versus 37% (95%CI, 0.27-0.48) in tumors with unknown receptors and 55% in platinum sensitive (95%CI, 0.28-0.80) versus 40% (95%CI, 0.29-0.51) in platinum resistant tumors The SOR for death calculated from 6 out of 9 randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy (SOR=0.69, 95%CI, 0.50-0.97), with a possible tendency for a greater effect in first line and low grade tumors. The overall quality of the RCTs was low. CONCLUSIONS: The activity of endocrine therapy in advanced EOC is worth considering and seems to support large properly designed randomized trials in the first treatment of hormone sensitive EOC.

Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer.

BACKGROUND: Abiraterone acetate is an effective drug for castration-resistant prostate cancer, but cardiac serious adverse events (SAEs) may occur. We studied their association with N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T (TnT) during abiraterone therapy. PATIENTS AND METHODS: In a single institution, 17 patients were treated with abiraterone acetate 1 g daily with concomitant prednisone and then switched to dexametasone plus canrenone. Blood samples for PSA, NT-proBNP, and TnT were obtained at baseline and after 1, 3, and 6 months. RESULTS: Five patients (29.4%) experienced G3 to 4 cardiac SAEs after a median of 13 weeks (range, 9-32), including pulmonary edema, heart failure, acute coronary syndrome, sinus bradycardia with syncope, and pulmonary edema. At baseline, 4 weeks, and 3 months, median NT-proBNP and TnT levels were higher in patients with subsequent cardiac SAEs (P= .03 and P= .04 for NT-proBNP and TnT at 3 months, respectively). After switching to dexametasone and introducing canrenone, no additional cardiac SAEs were noted. Overall response rate was 67%. CONCLUSIONS: Our study suggests a higher than expected risk of cardiac SAEs during abiraterone treatment which may well be due to the small sample size and the unrestricted entry criteria. However, baseline and frequent NT-proBNP and TnT monitoring predicted a higher risk for cardiac SAE. Larger studies should confirm our findings.

Raloxifene hydrochloride for breast cancer risk reduction in postmenopausal women.

INTRODUCTION: Raloxifene is an estrogen receptor modulator which competes with estrogens for binding to the estrogen receptor. Based on the results of the STAR (Study of Tamoxifen And Raloxifene) trial, raloxifene has been approved by the U.S. Food and Drug Administration for the reduction of breast cancer (BC) risk in postmenopausal women at increased risk. Areas covered: This analysis reviews the activity of raloxifene and the clinical trials for non-BC indications which led to investigate its use as BC preventive agent. We review the trial establishing its efficacy for BC prevention and the meta-analyses including different SERMs for BC prevention. Expert commentary: Compared with tamoxifen, raloxifene has shown a slightly lower efficacy in reducing BC risk and a better safety profile. Raloxifene also offers to postmenopausal women a benefit in terms of osteoporosis. Future research should investigate its use in premenopausal women and in association with other preventive agents.

Dual Block with Lapatinib and Trastuzumab Versus Single-Agent Trastuzumab Combined with Chemotherapy as Neoadjuvant Treatment of HER2-Positive Breast Cancer: A Meta-analysis of Randomized Trials.

PURPOSE: (Neo)adjuvant treatment with chemotherapy plus trastuzumab reduces recurrence and death risk in HER2-positive (HER2(+)) breast cancer. Randomized trials assessed HER2 dual block by adding lapatinib to trastuzumab and chemotherapy in the neoadjuvant setting using pathologic complete response (pCR) as the outcome measure. We conducted a meta-analysis of randomized trials testing neoadjuvant dual block with lapatinib and trastuzumab versus trastuzumab alone in HER2(+) breast cancer. EXPERIMENTAL DESIGN: Trials were identified by Medline (PubMed), ISI Web of Science (Science Citation Index Expanded), Embase, Cochrane library, and reference lists of published studies, review articles, editorials, and by hand-searched reports from major cancer meeting reports. RESULTS: Six randomized trials including 1,155 patients were identified, of whom 483 (41.8%) were hormone receptor-negative, 672 (58.2%) hormone receptor-positive, 534 (46.2%) received taxanes alone, and 621 (53.8%) anthracyclines plus taxanes or the docetaxel-carboplatin regimen. Overall, the dual block was associated with a significant 13% absolute improvement in pCR rate compared with single-agent trastuzumab (summary risk difference, SRD 0.13; 95% CI, 0.08-0.19). The activity was greater in hormone receptor-negative patients who received chemotherapy with taxanes alone (SRD 0.25; 95% CI, 0.13-0.37), compared to hormone receptor-positive or hormone receptor-negative disease treated with anthracyclines plus taxanes or the docetaxel-carboplatin regimen (SRD 0.09; 95% CI, 0.02-0.15; Pinteraction = 0.05). CONCLUSIONS: On the basis of ΔpCR data, the dual block with trastuzumab and lapatinib plus chemotherapy is a very active treatment only in HER2(+) and hormone receptor-negative breast cancer treated with taxane monochemotherapy. Clin Cancer Res; 22(18); 4594-603. ©2016 AACR.

Metformin: risk-benefit profile with a focus on cancer.

INTRODUCTION: Epidemiological evidence suggests an increased incidence of cancer in obese, prediabetic, and diabetic patients and a reduced risk of cancer incidence and mortality in diabetic patients on metformin compared with other antidiabetic drugs. In vitro studies support the efficacy of metformin in cancer therapy and prevention. Although metformin seems to be promising as a cancer chemopreventive or therapeutic drug, the principal consideration is whether metformin will be effective in cancer clinical trials for nondiabetic subjects or only in diabetics or subjects with insulin resistance. Safety of metformin is even more important in treating nondiabetic patients. AREAS COVERED: The present review focuses on epidemiological data and clinical trials testing the efficacy of metformin on cancer, the safety in nondiabetic patients and the future development of this promising drug. EXPERT OPINION: Meta-analyses of epidemiological in which metformin treatment has been used for diabetic patients show a positive trend for benefit; nevertheless, clinical data outcomes are preliminary and the results of ongoing trials are awaited. The different types of cancer, heterogeneity of populations and presence of comorbidity make it difficult to determine the benefits of metformin in cancer prevention and treatment.

Breast cancer incidence after hormonal treatments for infertility: systematic review and meta-analysis of population-based studies.

The increasing practice of hormonal infertility treatments (HITs) raised concerns about their effects on breast cancer (BC) risk. Available evidence reported conflicting results. The aim of this study was to assess the potential association between HITs and BC risk. The literature was searched through November 2014. Eligible studies included cohort studies reporting BC incidence in women undergone HITs. Data were analyzed with standard meta-analytic techniques. Subgroup analyses were performed by type of intervention (IVF vs. NO IVF), follow-up duration (<10 vs. >10 years), and type of control (population vs. infertile). 20 eligible studies (207.914 women, 2347 BC) were retrieved: no increased risk was detected (SRR = 1.05, 95 % CI 0.96-1.14), with a significant heterogeneity (I (2) = 59 %, p = 0.001) among studies. In the seven studies with the in vitro fertilization (IVF) procedure, no increase in BC risk was observed (SRR = 0.96, 95 % CI 0.80-1.14); in the three NO IVF studies, an increased BC risk was identified (SRR = 1.26, 95 %CI 1.06-1.50). A borderline interaction between type of intervention (IVF vs. NO IVF) and BC risk was observed (p = 0.06). An increased risk with longer follow-up (≥10 vs. <10 years) was detected (SRR = 1.13, 95 % CI 1.02-1.26 vs. SRR = 0.95, 95 % CI 0.85-1.06). Overall, HITs are not associated with an increased BC risk. In particular, no increased risk was observed in women undergoing IVF. Conversely, an increased in BC risk cannot be ruled out with older treatment protocols based on clomiphene. The long-term administration of clomiphene outside the current indications should be discouraged because of a possible increase in BC risk.

An observational study of nasal cavity toxicity in cancer patients treated with bevacizumab.

BACKGROUND: The nasal cavity is a vulnerable zone which may be damaged by vascular disorders. We systematically assessed the frequency and severity of nasal cavity alterations during bevacizumab treatment, to determine its clinical relevance and factors contributing to its onset. PATIENTS AND METHODS: We conducted a hospital-based cohort study in 47 consecutive patients with advanced cancers who were on treatment with chemotherapy and bevacizumab at different doses. All patients underwent otolaryngology (ENT) examination at the time of study initiation. RESULTS: The mean number of cycles at first ENT examination was 16 (standard deviation = 14). A total of 45 patients (96%) showed nose mucosal lesions, of whom 30% had erosions and 62% had grade 1 - 2 epistaxis. One patient had septal perforation. Grades 1 - 4 sinus disorders were noted in 60%. There was a significant trend to a higher risk of grade ≥ 2 nasal events for bevacizumab doses > 7.5 mg/kg, concomitant taxane use and digital nasal self-manipulation. CONCLUSIONS: We found a high incidence of nasal cavity lesions in patients receiving bevacizumab, with evidence for a dose-related effect. Most cases were low grade and manageable without drug interruption, but severe toxicity may rarely occur. Oncologists should be aware of this unusual event.

The Pan European Emesis Registry (PEER): a critical appraisal of the Italian experience.

PURPOSE: Data from a large European prospective observational study were analysed to describe the antiemetic prescribing pattern for chemotherapy-induced nausea and vomiting (CINV) in Italian clinical practice. METHODS: Post hoc analysis of the Pan European Emesis Registry in chemo-naïve adults initiating single-day highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer. RESULTS: A total of 211 eligible patients were enrolled in the Italian centres, 180 were included in the analyses for cycle 1; 50·6% received MEC. The use of guideline-consistent CINV prophylaxis (GCCP) varied substantially between acute and delayed phases (54·4% during the acute phase vs. 29·4% in the overall 120-hour study period, acute plus delayed phases). Neurokinin-1 receptor antagonist was added to the prophylaxis with dexamethasone+5-hydroxytryptamine type 3 receptor antagonists in only 11·1% of patients (vs. 57·2% of the entire European study population). In the GCCP group, the complete response rate was significantly higher than that recorded in the guideline-inconsistent CINV prophylaxis (GICP) group (75·5 vs. 53·5%, P = 0·006). CONCLUSION: The proportion of guideline-consistent antiemetic therapy was quite low in the Italian population as it was in the overall European population. The implementation of specific guidelines' recommendations for chemotherapeutic regimens administered according to standard protocols could be considered as a means to reduce the burden of CINV.