Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.

BACKGROUND: Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. METHODS: In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. FINDINGS: Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. INTERPRETATION: Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. FUNDING: American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Identification and Characterization of Nasal Polyposis and Mycoplasma Superinfection by Scanning Electron Microscopy and Nasal Cytology with Optical Microscopy: A Case Report.

Nasal polyposis is characterized by benign, non-cancerous and painless growths originating in the tissue of the nasal cavities and paranasal sinuses. Polyps arise from chronic inflammation due to asthma, recurrent infections, allergies, drug sensitivity or immune disorders. They can obstruct the nasal cavities and thus cause respiratory problems, a reduction in the sense of smell and susceptibility to infections. Furthermore, nasal polyps can recur. Hence the importance of using valid diagnostic methods. In this work, the diagnostic investigation carried out by scanning electron microscopy (SEM) and nasal cytology led, for the first time, to the identification of a mycoplasma superinfection on nasal polyposis.

Clinical and pathological factors predictive of response to neoadjuvant chemotherapy in breast cancer: A single center experience.

Neoadjuvant chemotherapy (NAC) of breast cancer (BC) improves outcomes, especially in patients with locally advanced and inflammatory cancer. Further insight into clinic-pathological factors influencing outcomes is essential to define the optimal therapeutic strategy for each category of patients and to predict the response to the treatment. In total, 117 patients with BC were treated with NAC with or without trastuzumab between 2010 and 2015. The histologic response to NAC was defined as a pathological complete response (pCR) when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Relapse-free survival (RFS) was estimated using the Kaplan-Meier method and compared using log rank analysis. P-value <0.05 was considered statistically significant. The median age of the 117 patients enrolled in the present study was 52 years (age range, 35-85 years). The overall response rate (complete and partial responses) assessed by radiological and pathological evaluation were 76 and 72%, respectively. pCR was achieved in 35 out of 117 patients (~30%). In total, 6 patients (5%) developed progressive disease during chemotherapy. The RFS was 85 months (SE=3; 95% CI 79-91). The median was not reached and the mean follow-up time was 55 months (median 52 months; range 11-100 months). In this time, 20 patients (17%) experienced tumor recurrence. From the univariate analysis, the pathological response was significantly associated with receptor-based subtype, menopausal status and T-stage. From the multivariate analysis by using linear multiple regression and including receptor- menopausal status and T-stage, the model was not significant (P=0.062). However, by using the multiple logistic regression, and including age, pCR was significantly associated with ER+ HER2neg (P=0.006), T2 (P=0.043) and T3 (P=0.018). T-stage, menopausal status and receptor status are significantly associated with the pathological response in patients with inoperable BC treated with NAC.

Efficacy and Safety of Cetuximab plus Radiotherapy in Cisplatin-Unfit Elderly Patients with Advanced Squamous Cell Head and Neck Carcinoma: A Retrospective Study.

INTRODUCTION: Concurrent platinum-based chemoradiation currently represents the standard treatment for advanced head and neck cancer (HNC), but it induces a significant toxicity, in particular among elderly patients. Elderly and unfit patients have been underrepresented in clinical trials and there is a need for tailored guidelines. METHODS: A retrospective review of clinical data of HNC patients treated at the Operative Oncology Unit of the San Giovanni di Dio Hospital in Frattamaggiore (Naples, Italy) was performed. At study entry, a comprehensive assessment including absolute contraindications for cisplatin use, as well as comorbidities, socioeconomic status, BMI, and weight loss, was performed. The treatment included high-dose radiotherapy plus weekly cetuximab (initially at a dose of 400 mg/m2of body surface area and thereafter at 250 mg weekly during the whole radiotherapy). The aim of this study was to evaluate the activity and toxicity of this schedule in a series of patients aged older than 69 years. RESULTS: Between May 30, 2013, and March 30, 2015, sixty-four patients (age range, 69-87 years; median age, 73.7 years; male/female ratio, 46/18) were treated. The overall response rate was 67% in this series of patients. The disease control rate was 76%. Disease progression was recorded in 25% of the patients. The median duration of loco-regional control was 17 months (range, 15.8-17.7 months). PFS was 14.8 months (range, 13.9-15.5 months). The overall survival was 34 months, with a median follow-up of 41.0 months (range, 31.1-36.8 months). The main grade 3/4 adverse events were acne rash in 52% and radiation dermatitis in 32% of the cases. CONCLUSION: Cetuximab plus radiotherapy appears to be feasible and active in elderly patients unsuitable for cisplatin treatment. The treatment was supported by a favorable toxicity profile.

A giant left atrial mass-Clinical treatment dilemma.

A 74-year-old female current 75 pack-year smoker presented with shortness of breath and mild hemoptysis. Chest computed tomography showed a large right upper lobe mass compressing the superior vena cava, invading the right pulmonary veins, and occupying the majority of the left atrium. Brain magnetic resonance imaging revealed a 13 mm right parietal lesion with surrounding edema consistent with metastasis. A 3D TEE showed a large mobile mass in the left atrium. Bronchoscopy confirmed that the tumor mass was consistent with a moderately to poorly differentiated squamous cell carcinoma. She underwent chemotherapy, radiation, and immune therapy. She was also started on warfarin for anticoagulation after the initial chemotherapy with resolution of the left atrial mass. We feel that the patient most likely had carcinogenic thrombus in the pulmonary veins and left atrium.

Nasal and systemic eosinophilia associated with solid intestinal tumors, a case report and review of the literature.

The authors report the study of a clinical case, which presented eosinophilia both in the secretion of the nasal mucosa and in the blood count. After a careful examination of all the pathologies related to hypereosinophilia, through a clinical study, they have documented the presence of an adenocarcinoma located in the ileocecal junction of the colon. From what has been documented it is clear that only a clinical observation of precision, carried out above all through nasal cytology and colonoscopy, is able to diagnose an important pathology, such as oncology. For the literature review we used the Scopus and PubMed search engines to analyze other authors who were interested in the relationship between eosinophilia and colorectal cancer. Much of the studies analyzed reported a close relationship between the presence of tissue eosinophilia and tumor, and the prognosis of colorectal cancer. KEY WORD: Colorectal cancer, Eosinophils, Hypereosinophilia.

EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes.

PURPOSE: Approximately 3% to 10% of EGFR (epidermal growth factor receptor) -mutant non-small cell lung cancers (NSCLCs) undergo transformation to small-cell lung cancer (SCLC), but their clinical course is poorly characterized. METHODS: We retrospectively identified patients with EGFR-mutant SCLC and other high-grade neuroendocrine carcinomas seen at our eight institutions. Demographics, disease features, and outcomes were analyzed. RESULTS: We included 67 patients-38 women and 29 men; EGFR mutations included exon 19 deletion (69%), L858R (25%), and other (6%). At the initial lung cancer diagnosis, 58 patients had NSCLC and nine had de novo SCLC or mixed histology. All but these nine patients received one or more EGFR tyrosine kinase inhibitor before SCLC transformation. Median time to transformation was 17.8 months (95% CI, 14.3 to 26.2 months). After transformation, both platinum-etoposide and taxanes yielded high response rates, but none of 17 patients who received immunotherapy experienced a response. Median overall survival since diagnosis was 31.5 months (95% CI, 24.8 to 41.3 months), whereas median survival since the time of SCLC transformation was 10.9 months (95% CI, 8.0 to 13.7 months). Fifty-nine patients had tissue genotyping at first evidence of SCLC. All maintained their founder EGFR mutation, and 15 of 19 with prior EGFR T790M positivity were T790 wild-type at transformation. Other recurrent mutations included TP53, Rb1, and PIK3CA. Re-emergence of NSCLC clones was identified in some cases. CNS metastases were frequent after transformation. CONCLUSION: There is a growing appreciation that EGFR-mutant NSCLCs can undergo SCLC transformation. We demonstrate that this occurs at an average of 17.8 months after diagnosis and cases are often characterized by Rb1, TP53, and PIK3CA mutations. Responses to platinum-etoposide and taxanes are frequent, but checkpoint inhibitors yielded no responses. Additional investigation is needed to better elucidate optimal strategies for this group.

Correlation between various trace elements and ultramicroscopic structure of epiretinal macular membranes and glial cells.

INTRODUCTION: Elements such as zinc, iron, copper, sulphur and phosphorus have been identified in retinal layers and implicated in vital retinal functions. Regarding mineral composition of epiretinal membranes (ERMs), literature is lacking. This study aimed to analyze both mineral composition and anatomical ultrastructure of ERMs to clarify the pathophysiology of this disease. METHODS: Twenty ERMs (10 diabetic ERMs and 10 idiopathic ERMs) from 20 patients were harvested during pars plana vitrectomy. Scanning Electron Microscopy (SEM) was used to investigate the anatomical ultrastructure of the peeled ERMs. Mineral composition was analyzed using energy-dispersive spectrometry (EDS). The most frequent elements were evaluated in relation to appearance of ERMs analyzed at SEM and at OCT images. RESULTS: Sulphur was the most frequent element found (in 80% of the samples), followed by sodium (50%) and phosphorus (45%). The presence of these elements was not significantly different between diabetic and idiopathic ERMs (P >0.05). Using SEM we found a folded tissue in all ERMs, except in 4 ERMs, where we observed only a smooth tissue. There was a trend of sodium to be more frequent in ERMs with folded layers at SEM examination. CONCLUSIONS: Several elements were identified in ERMs, and sulphur, sodium and phosphorus were the most frequent ones. This finding may help to understand their role in the physiopatology of epiretinal proliferation and in glial activation.

Anterior-Segment Optical Coherence Tomography and Scanning Electron Microscopy to Evaluate Corneal Epithelial Changes in Patients Undergoing Glaucoma Therapy.

PURPOSE: To measure corneal epithelial thickness (CET) in patients with glaucoma using anterior-segment optical coherence tomography and to evaluate CET changes in relation to corneal epithelial microvilli analyzed by scanning electron microscopy (SEM). METHODS: Twenty-two eyes (16 patients) being treated with preservative-containing topical medications and 12 normal eyes underwent anterior-segment optical coherence tomography imaging using RTVue-100. The CET maps generated corresponded to a 6-mm diameter area of cornea that was divided into 17 sectors. We compared the CETs of each sector obtained in the glaucomatous group with those obtained in the control group. RESULTS: Glaucomatous eyes were divided into 2 groups based on the number of microvilli on SEM: group 1 (6 eyes) = grades 1 and 2 at SEM (range: 500-3000) and group 2 (10 eyes) = grades 3 and 4 at SEM (range: 0-500). Four CET sectors were significantly thinner in group 1 than in normal eyes: central (P = 0.012), superior (P = 0.005), temporal paracentral (P = 0.003), and temporal midperipheral (P = 0.023). No significant differences were observed between group 2 and normal eyes. CET sectors were significantly thinner in group 1 than in group 2 only in the superior (P = 0.024) and superior-temporal paracentral (P = 0.020) sectors. CET progressively increased in patients with glaucoma as the number of corneal epithelial microvilli decreased. CONCLUSIONS: CET and corneal epithelial microvilli are new parameters with which to evaluate early stages of corneal epithelial changes during glaucoma therapy. In advanced stages of corneal epithelial damage, SEM evaluation reveals ultrastructural epithelial changes that may not be observed on CET measurements.

Maintenance Therapy with Biweekly Cetuximab: Optimizing Schedule Can Preserve Activity and Improves Compliance in Advanced Head and Neck Cancer.

OBJECTIVES: This study evaluates maintenance cetuximab administered every 2 weeks (q2w) after chemotherapy plus cetuximab as first-line treatment in a series of patients with head and neck squamous cell cancer and compares the results with those obtained in a historical control group of patients receiving weekly cetuximab. METHODS: After chemotherapy plus cetuximab as first-line treatment, in Group A, 36 patients enrolled from October 2016 to November 2017, received biweekly cetuximab, administered at 500 mg/m2. Group B was a control group of patients treated at our institution from August 2015 to September 2016 and received weekly infusion of cetuximab at 250 mg/m2. RESULTS: Confirmed overall response rates were, respectively, 19% for Group A and 17% for Group B according to intention-to-treat analysis. During the maintenance treatment, median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 4.8 and 4.4 months; OS, 9.0 and 7.9 months; in Groups A and B, respectively). The most common adverse events among treated subjects included fatigue, rash, and hypomagnesemia. CONCLUSION: Maintenance therapy with simplified biweekly cetuximab is a convenient, effective, and well-tolerated regimen in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

Reactivation of hepatitis B virus in cancer patients treated with chemotherapy for solid tumors. Is the prophylaxis really required?

BACKGROUND: Reactivation of hepatitis B virus during cancer chemotherapy for non-hematological tumors is not fully clear. AIM: To evaluate the risk of hepatitis B virus reactivation in carriers of hepatitis B virus cancer patients treated with chemotherapy for solid tumors. METHODS: Two hundred sixty-seven patients with solid tumors were consecutively enrolled: 13 (4.8%) were hepatitis B s-antigen positive, of whom 6 were documented inactive carriers and 7 had chronic liver disease. Thirty-two patients (12%) were hepatitis B s-antigen negative/hepatitis B c-antibody positive. Hepatitis B virus inactive carriers were followed every 3 months by alanine aminotransferases, hepatitis B virus-DNA; whereas hepatitis B virus occult carriers were followed every 3 months by alanine aminotransferases and hepatitis B s-antigen. RESULTS: None of the 38 total patients with inactive or occult B infection who did not receive prophylaxis presented hepatitis B virus reactivation during the follow-up period. CONCLUSION: This study suggests that, in hepatitis B s-antigen negative patients who undergo chemotherapy for solid tumors, hepatitis B and c-antibody screening results are not relevant to clinical decision and can be avoided. Larger studies are needed to establish whether the risk of reactivation of HBV during chemotherapy is negligible in this subset of patients and they could not be monitored for HBV reactivation.

Adherence and safety of regorafenib for patients with metastatic colorectal cancer: observational real-life study.

AIM: In this prospective multicenter real-life observational cohort study, we investigated the acceptance, adherence and safety of regorafenib, in the treatment of metastatic colorectal cancer patients. PATIENTS & METHODS: A total of 136 patients were recruited at six oncological hospital sites in southern Italy. The adherence to the treatment was measured with patient-completed medication diaries, physician interviews and pill counts. RESULTS: We found a statistically significant improvement of therapy adhesion by the acceptance questionnaire. The Eastern Cooperative Oncology Group performance status, the level of acceptance, the educational level and the concomitant usage of oral medications influenced the adherence to the treatment. CONCLUSION: Patients' level of education, concomitant other oral medications and patients' general clinical condition may influence the adherence to regorafenib.

Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strategies for treatment of advanced hepatocellular carcinoma must be compared with the results obtained with sorafenib, but no new drug or drug combination has yet achieved better results. In our opinion, the efforts to impact the natural history of the disease will be directed not only to drug development but also to understanding the underlying liver disease (usually hepatitis B virus- or hepatitis C virus-related) and to interrupting the progression of cirrhosis. It will be important to define the role and amount of mutations in the complex pathogenesis of hepatocellular carcinoma and to better integrate locoregional and systemic therapies. It will be important also to optimize the therapeutic strategies with existing chemotherapeutic drugs and new targeted agents.

Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas.

Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed.

Assessment of conjunctival microvilli abnormality by micro-Raman analysis - by G. Rusciano et al.

Conjunctival microvilli are microscopic cellular membrane protrusions on apical epithelial cells, which increase the surface area available for tear adherence. Pathological alterations of microvilli structure affect the tear film stability and, conversely, dysfunctions of tear film composition can lead to a suffering epithelium (dry-eye syndrome). In this work we propose the use of micro-Raman analysis to reveal conjunctival microvilli abnormalities. Samples were obtained by impression cytology from patients by different stage of dry-eye syndrome. Our experimental outcomes demonstrate that Raman analysis, combined with the use of Principal Component Analysis, is able to detect different stages of microvilli reduction. Globally, these results hold promise for the use of Raman analysis for an objective, effective, non-invasive and potentially also in-vivo analysis of the conjunctiva in all the cases of microvilli-related ocular pathologies.

Relationship between gastroesophageal reflux disease and Ph nose and salivary: proposal of a simple method outpatient in patients adults.

INTRODUCTION: The frequency of gastroesophageal reflux disease (GERD) is increasing, in part through easy inspection of the upper digestive tract, but especially for a real spread of the disease as a consequence of modernity, lifestyle, incorrect dietary rules, and stress arising from social norms. It is a common chronic gastrointestinal disorder in Europe and the United States. MATERIALS AND METHODS: The aim of our study is to highlight a relationship between gastroesophageal reflux disease and salivary pH as evidenced by indicator strips, especially in the outpatient field. Twenty adult subjects (10 males and 10 females) aged between 18 and 50 years (GROUP A)_ were selected. How to control a homogeneous group of 20 patients without GERD, or from any type of allergies (GROUP B) was enlisted. RESULTS: This method has provided excellent results showing no difference in the measured values compared with the traditional instrumental measurement. CONCLUSION: Our study has allowed us to observe a strong correlation between the saliva pH, nasal cavities and the interaction between the two districts, and could be the basis for a diagnosis of GERD especially in primary health care clinics and in the initial stage of the disease.

Study on the Protective Effect of a New Manganese Superoxide Dismutase on the Microvilli of Rabbit Eyes Exposed to UV Radiation.

We present a study on the protective effects against UV radiation of a gel formulation containing a new recombinant form of manganese superoxide dismutase on the conjunctiva and corneal epithelia of rabbit eyes. The integrity of the microvilli of both ocular tissues has been considered as an indicator of the health of the tissues. Samples, collected by impression cytology technique, were added of 80 µL of a gel formulation containing superoxide dismutase (2.0 µg/mL) and irradiated with UV rays for 30 minutes and were evaluated with scanning electron microscopy. Wilcoxon test was used to verify the possible occurrence of statistically significant differences between damage for treated and nontreated tissues. Application of gel produces a significant reduction of damage by UV irradiation of ocular epithelia; both epithelia present a significant reduction of damaged microvilli number if treated with the superoxide dismutase gel formulation: the p values (differences between damage found for treated and nontreated both ocular tissues) for conjunctiva and cornea samples were p ≪ 0.01 and p ≪ 0.0001, respectively, at confidence level of 95%. The administration of this gel formulation before UV exposure plays a considerable protective role in ocular tissues of rabbit eye with a significant reduction of the damage.

Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer.

PURPOSE: TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m(2)), gemcitabine plus TH-302 240 mg/m(2) (G+T240), or gemcitabine plus TH-302 340 mg/m(2) (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. RESULTS: Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (-5,398 v -549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302-related AEs but were not associated with treatment discontinuation. CONCLUSION: PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979).