Safety and efficacy analysis of neoadjuvant pertuzumab, trastuzumab and standard chemotherapy for HER2-positive early breast cancer: real-world data from NeoPowER study.

BACKGROUND: The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real-world population. METHODS: We retrospectively reviewed the medical records of stage II-III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables. RESULTS: 260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009). CONCLUSIONS: Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.

First-line treatment of metastatic castration-resistant prostate cancer: the real-world Italian cohort of the Prostate Cancer Registry.

BACKGROUND: With the availability of multiple treatment options for metastatic castration-resistant prostate cancer (mCRPC), new real-world data on disease management and drugs' performance are needed. METHODS: We described characteristics, management and clinical outcomes of patients receiving first-line mCRPC treatment within the Italian cohort of the real-world, prospective, international Prostate Cancer Registry. Patients were enrolled consecutively (2013-2016) in 32 Italian sites and followed for 3 years. RESULTS: 238 patients were included: 157 received first-line abiraterone acetate plus prednisone ("abiraterone" thereafter) and 70 first-line docetaxel; 11 patients receiving other treatments were not considered. Compared with docetaxel-treated patients, those receiving abiraterone were significantly older (age ⩾75: 63.7% vs 38.6%), less frequently had a Gleason score >8 (48.2% vs 67.6%, p<0.005) at initial diagnosis, and more frequently an ECOG score ⩾1 (52.7% vs 36.2%, p<0.05) and comorbidities (76.4% vs 57.1%, p<0.05) at baseline; they reported a lower analgesic use (15.3% vs 30%, p<0.005). In the abiraterone group (median follow-up 22.1 months), median time to progression (TTP) and progression-free survival (PFS) were, respectively, 14.4 months (95% confidence interval, CI, 10.6-18.0) and 13.0 months (95% CI, 9.1-16.8); median overall survival (OS) was not reached, and 3-year OS was 59.1%. In the docetaxel treatment group (median follow-up 25.3 months), median TTP, PFS and OS were, respectively, 8.2 months (95% CI, 6.1-10.3), 8.2 months (95% CI, 5.8-10.3) and 33.2 months (95% CI, 19.2-not estimable). CONCLUSION: This investigation provided valuable information on the overall mCRPC treatment pattern and the effectiveness of first-line abiraterone and docetaxel in a population representative of everyday practice.

Iatrogenic Ocular Surface Diseases Occurring during and/or after Different Treatments for Ocular Tumours.

The ocular surface represents a finely regulated system that allows the protection of the eye. It is particularly susceptible to different treatments for intraocular tumours, such as uveal melanoma and conjunctival cancers. Traditionally, the management of ocular tumours depends on the characteristics of the lesion, and is based on a combination of selective surgery, topical chemotherapy, and/or radiotherapy delivered through different mechanisms (e.g., charged-particle radiotherapy or brachytherapy). Possible complications involving the ocular surface range from transient dry eye disease or keratitis up to corneal melting and perforation, which in any case deserve careful evaluation for the risk of permanent sigh-threatening complications. Clinicians involved in the management of these patients must be aware of this risk, in order to reach an early diagnosis and promptly set up an adequate treatment. The present review of the literature will summarize acute and chronic complications affecting the ocular surface following different therapies for the treatment of ocular tumours.

Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer.

BACKGROUND: The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity. PATIENTS AND METHODS: This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m2 intravenously (i.v.) on day 1, docetaxel, 30 mg/m2 i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle. RESULTS: Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5-53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06-1.30, p = 0.11). Toxicity included grade 3-4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1-2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1-2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase. CONCLUSIONS: The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens.

Effective Containment of a COVID-19 Subregional Outbreak in Italy Through Strict Quarantine and Rearrangement of Local Health Care Services.

BACKGROUND: Since the beginning of the pandemic, the epidemiology of coronavirus disease 2019 (COVID-19) in Italy has been characterized by the occurrence of subnational outbreaks. The World Health Organization recommended building the capacity to rapidly control COVID-19 clusters of cases in order to avoid the spread of the disease. This study describes a subregional outbreak of COVID-19 that occurred in the Emilia Romagna region, Italy, and the intervention undertaken to successfully control it. METHODS: Cases of COVID-19 were defined by a positive reverse transcriptase polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab. The outbreak involved the residential area of a small town, with ~10 500 inhabitants in an area of 9 km2. After the recognition of the outbreak, local health care authorities implemented strict quarantine and a rearrangement of health care services, consisting of closure of general practitioner outpatient clinics, telephone contact with all residents, activation of health care units to visit at-home patients with symptoms consistent with COVID-19, and a dedicated Infectious Diseases ambulatory unit at the nearest hospital. RESULTS: The outbreak lasted from February 24 to April 6, 2020, involving at least 170 people with a cumulative incidence of 160 cases/10 000 inhabitants; overall, 448 inhabitants of the municipality underwent at least 1 nasopharyngeal swab to detect SARS-CoV-2 (positivity rate, 38%). Ninety-three people presented symptoms before March 11 (pre-intervention period), and 77 presented symptoms during the postintervention period (March 11-April 6). CONCLUSIONS: It was possible to control this COVID-19 outbreak by prompt recognition and implementation of a targeted local intervention.

Fighting cancer in coronavirus disease era: organization of work in medical oncology departments in Emilia Romagna region of Italy.

Aim: To assess the measures applied to reduce the spread of coronavirus disease (COVID-19) and the timing of their application in medical oncology departments. Materials & methods: We surveyed all medical oncology departments from the Italian Emilia Romagna region via a multidomain questionnaire. The questions covered items on patients, healthcare workers, risk reduction measure and clinical trials. Results: A total of 12 centers involving 861 healthcare members joined the survey. The measures applied to patients and health workers partially converged in all the departments while major divergences were found in the clinical trials domain. High rate of COVID-19 infection occurred among medical doctors (21/208, 10.1%) and social care workers (13/110, 11.8%). Rate of infection among nurses was 5.7% (24/418). Conclusion: All measures able to reduce risk of COVID-19 infection must be applied in medical oncology departments. Early introduction of risk reduction measures may be a critical issue.

The Role of Nutrition and Nutritional Supplements in Ocular Surface Diseases.

Dry eye disease (DED) is a multifactorial disease of the ocular surface system whose chore mechanisms are tear film instability, inflammation, tear hyperosmolarity and epithelial damage. In recent years, novel therapies specifically targeting inflammation and oxidative stress are being investigated and used in this field. Therefore, an increasing body of evidence supporting the possible role of different micronutrients and nutraceutical products for the treatment of ocular surface diseases is now available. In the present review, we analyzed in detail the effects on ocular surface of omega-3 fatty acids, vitamins A, B12, C, D, selenium, curcumin and flavonoids. Among these, the efficacy of omega-3 fatty acid supplementation in ameliorating DED signs and symptoms is supported by robust scientific evidence. Further long-term clinical trials are warranted to confirm the safety and efficacy of the supplementation of the other micronutrients and nutraceuticals.

Impact of influenza syndrome and flu vaccine on survival of cancer patients during immunotherapy in the INVIDIa study.

Aim: INVIDIa was a retrospective, multicenter study, exploring the clinical efficacy of influenza vaccine in 300 cancer patients undergoing immunotherapy. Overall survival (OS) was immature at the initial report. Methods: We reported the final OS analysis from the original study population and within subgroups. Results: Both at the univariate and multivariate analysis, the occurrence of influenza syndrome (IS) was significantly related to better OS in the overall population (OR: 0.53 [95% CI: 0.32-0.88]; p = 0.01). In the lung cancer subgroup, receiving flu vaccine and/or developing IS was related to better OS (p = 0.04). Within elderly patients, the flu vaccine was the main variable for the relative OS advantage (p = 0.05). Conclusion: Receiving the flu vaccine and/or developing IS was related to better OS within the INVIDIa population.

Second line therapy with axitinib after only prior sunitinib in metastatic renal cell cancer: Italian multicenter real world SAX study final results.

BACKGROUND: This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. METHODS: 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. RESULTS: PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. CONCLUSIONS: Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT - Napoli - 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it.

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a transversal challenge. The INVIDIa study.

AIM: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. METHODS: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017. RESULTS: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001. CONCLUSION: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy.

Negative prognostic factors and resulting clinical outcome in patients with metastatic renal cell carcinoma included in the Italian nivolumab-expanded access program.

AIM: We report the outcomes observed with nivolumab in metastatic renal cell carcinoma patients with poor prognostic features enrolled in the Italian expanded access program. PATIENTS & METHODS: Nivolumab was available for patients who relapsed after at least one prior systemic treatment in the advanced or metastatic setting. RESULTS: Of 389 patients, 32 (8%) had brain metastasis, 129 (33%) had liver and 193 (50%) had bone metastasis. These subpopulations achieved a disease control rate of 53, 45 and 47%, respectively. Fifty-one patients had G4 tumor, and they showed 23% objective response rate. The safety profile of the subgroups was in line with the expanded access program population. No new safety signals were reported. CONCLUSION: Patients with poor prognostic features may derive relevant benefits from nivolumab.

A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy.

AIMS AND BACKGROUND: In addition to bone marrow suppression and renal toxicity, neurotoxicity is a commonly occurring side effect of widely used chemotherapeutic agents like taxanes, cisplatin and vinca alkaloids. Neurotoxicity can cause antitumor therapy discontinuation or dose regimen modification. The aim of the present exploratory study was to investigate the activity of acetyl-L-carnitine in reversing peripheral neuropathy in patients with chemotherapy-induced peripheral neuropathy. METHODS AND STUDY DESIGN: Twenty-seven patients (16 males and 11 females) with paclitaxel and/or cisplatin-induced neuropathy (according to WHO recommendations for the grading of acute and subacute toxic effects) were enrolled. Patients received at least one cisplatin- (n = 5) or one paclitaxel- (n = 11) based regimen, or a combination of both (n = 11). Patients with chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1 g/die i.v. infusion over 1-2 h for at least 10 days. RESULTS: Twenty-six patients were evaluated for response having completed at least 10 days of acetyl-L-carnitine therapy (median, 14 days; range, 10-20). At least one WHO grade improvement in the peripheral neuropathy severity was shown in 73% of the patients. A case of insomnia related to ALC treatment was reported in one patient. Acetyl-L-carnitine seems to be an effective and well-tolerated agent for the treatment of chemotherapy-induced peripheral neuropathy. CONCLUSIONS: Our preliminary results should be confirmed in double-blind, placebo controlled studies.

Phase II study of gemcitabine-cisplatin-paclitaxel triplet as induction chemotherapy in inoperable, locally-advanced non-small cell lung cancer.

PURPOSE: Our objective was to determine the activity in terms of response rate, surgical resectability, and the tolerability of the new three-drug combination gemcitabine-cisplatin-paclitaxel (GCP) in unresectable stage IIIA(N2) and IIIB non-small cell lung cancer (NSCLC). PATIENT AND METHODS: Forty-two chemo-naive patients with stage IIIA(N2)-IIIB NSCLC, median age of 59 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and the ability to tolerate pneumectomy, received gemcitabine (Gem) 1000 mg/m(2) IV days 1 and 8, cisplatin (CDDP) 50 mg/m(2) IV days 1 and 8, paclitaxel 125 mg/m(2) 1h infusion IV days 1 and 8, every 21 days for 3 cycles. After induction chemotherapy, patients were evaluated for surgery or definitive radiotherapy. RESULTS: Grade 3-4 neutropenia was the main hematologic toxicity, occurring in 28% of patients. Grade 3-4 thrombocytopenia was observed in only 11% of cases. No neutropenic fever or bleeding episodes were recorded. Severe non-hematologic toxicity was uncommon. Thirty (71%, 95% CI: 57.2-84.7%) of the 42 eligible patients had objective responses (1 complete and 29 partial responses). After induction chemotherapy, 21 patients (50%) went to surgery. Complete resection was obtained in 16 patients (38%). Viable tumor was present in 18 of 21 resection specimens. In three cases only necrotic tumor cells were identified, for a pathological complete response of 7%. With a median follow-up of 13.9 months, median time to progression was 17.4 months, median survival 21.7 months and estimated 1-year survival 92%. CONCLUSIONS: GCP combination is active and well tolerated in locally-advanced, non-resectable NSCLC. The activity profile, in terms of response and surgical resection rate, is comparable to that obtained with standard doublets.

Gemcitabine and cisplatin as induction chemotherapy for patients with unresectable Stage IIIA-bulky N2 and Stage IIIB nonsmall cell lung carcinoma: an Italian Lung Cancer Project Observational Study.

BACKGROUND: The objective of this trial was to evaluate the activity and safety of one of the newer platinum-based doublets as a neoadjuvant regimen in patients with unresectable Stage IIIA-bulky N2 and Stage IIIB nonsmall cell lung carcinoma (NSCLC). METHODS: From June 1996 to April 2000, 129 consecutive patients with locally advanced NSCLC were treated with gemcitabine, 1000 mg/m(2) on Days 1 and 8 and cisplatin, 70 mg/m(2) on Day 2 (GC) of a 21-day treatment cycle, for 4 cycles, as part of a combined-modality approach. RESULTS: After induction chemotherapy, 80 patients (62%; 95% confidence interval, 53.6-70.4%) achieved a partial response, 43 patients (33%) had stable disease, and 6 patients (5%) had disease progression during chemotherapy. Forty patients (31%), were considered resectable and underwent thoracotomy. Complete resectability was obtained in 38 patients (29%), with 2% of patients achieving a pathologic complete response. After surgery, 9 patients with Mountain Classification Stage IIIA NSCLC and 9 patients with Stage IIIB NSCLC received definitive adjuvant radiotherapy. Forty-six of 52 patients with Stage IIIB disease and 24 of 37 patients with Stage IIIA disease who were not considered suitable for surgery received definitive radiotherapy. The median time to disease progression was 11.4 months, the median survival was 19.4 months (range, 1.2-55.2 + months), and the 1-year survival rate was 74%. The lungs (33%) and the brain (21%) were the main sites of recurrence. Major toxicity was comprised of Grade 3-4 thrombocytopenia, which occurred in 34 patients (27%). CONCLUSIONS: GC administered according to a 3-week schedule was a highly active and safe regimen in patients with primary, unresectable, locally advanced NSCLC.

Índice de sobrecarga vascular e pressäo arterial como indicadores de variaçäo tensional sistólica após induçäo anestésica com propofol em pacientes normotensos e hipertensos / Vascular overload index and blood pressure as predictors of systolic blood pressure changes following anesthestic induction with propofol in normotensive and hypertensive patients

Justificativa e objetivos: o índice de sobrecarga vascular (IV=1,33 PAS - 0,33 PAD -133) é um indicador do risco hipertensivo cardiovascular, que se correlaciona com a ocorrência de episódios hipotensivos durante a anestesia. Este estudo avaliou as pressöes arteriais sistológica, diastológica e média e o ISV como indicadores da magnitude da variaçäo tensional sistólica, após a administraçäo de propofol. Método: foram estudados prospectivamente 100 pacientes, estado físico ASA I e II, divididos em dois grupos: grupo N, normotensos e grupo H, hipertensos tratados. A anestesia foi induzida com propofol (2mg.kg(elevado a menos 1)). A frequencia cardíaca (FC) e as pressöes arteriais sistólica (PAS), diastólica (PAD) e média (PAM) foram medidas, antes (M1) e após (M2) a administraçäo de propofol. O ISV e a pressäo de pulso (PP) foram calculados a partir da pressäo arterial obtida em M1. A variaçäo tensional sistólica foi calculada pela fórmula (VTS=PAS(M2) -PAS)m1)). Resultados: ocorreu significativa diminuiçäo da PAS em ambos os grupos, sendo maior no grupo H. No grupo H os coeficientes de correlaçäo entre a VTS e os parâmetros PAS, PP e ISV foram -0,84, -0,82 e -0,86, respectivamente. Os coeficientes de correlaçäo para PAD e PAM näo foram significativos. No grupo N os coeficientes de correlaçäo entre a VTS e os parâmetros PAS, PAD, PP, PAM e ISV foram respectivamente -0,34, -0,23, -0,27, -0,36 e -0,35 (p<0,05). Conclusöes: a pressäo arterial sistólica, a pressäo de pulso e o índice de sobrecarga vascular prévios à induçäo correlacionam-se fortemente com a magnitude da reduçäo tensional sistólica em pacientes hipertensos tratados