Hematological Toxicity During Concomitant Treatment With Ruxolitinib and Avelumab for Merkel Cell Carcinoma.

Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer. It frequently emerges in the presence of immunosuppression states such as myeloproliferative syndrome (MS). MS is treated with ruxolitinib, a selective JAK1 and JAK2 inhibitor. Avelumab, an anti PDL-1 inhibitor, is the standard treatment for MCC. To date it is unknown if avelumab and ruxolitinib have a synergistic or antagonistic effect when used together. Methods: We have identified all patients diagnosed with MCC, treated with avelumab, concomitant ruxolitinib, belonging to Tortora Hospital, Pagani and Santa Maria La Pietà Hospital, Nola, Italy between June 1 2019 and April 1 2020. Results: Among six MCC patients, we have found two patients in treatment with concomitant drugs. Both patients were being treated with ruxolitinib for MS as a standard regimen without suffering any hematological side effects. After starting doses of avelumab, we found thrombocytopenia, leukopenia, and anemia after cycle 1 and cycle 4, respectively, and decided to suspend both treatments. Following the suspension, the hematological values improved allowing us to restart treatment with avelumab without the need to resume ruxolitinib treatment. Conclusions: The combined treatment of ruxolitinib and avelumab demonstrated severe toxicity. Modifying the schedule or reducing the dose of both drugs needs to be studied in order to be able to treat both pathologies.

COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature.

BACKGROUND: It is reasonable to think that cancer patients undergoing chemotherapy, targeted therapy or immunotherapy could have a more aggressive course if positive for Coronavirus disease CoV-2 (COVID- 19). METHODS: We conducted a literature review on https://www.ncbi.nlm.nih.gov/pubmed/, https://scholar.google.com, www.arxiv.org, www.biorxiv.org, of all articles published using the keywords COVID-19 therapy or treatment and cancer until May 2, 2020. A total of 205 articles were identified and 53 were included in this review. RESULTS: We describe the ongoing COVID-19 therapies that should be known by oncologists and highlight the potential interactions with antineoplastic drugs, commonly used in clinical practice. The main drug interactions were found with tocilizumab, ruxolitinib and colchicine. CONCLUSIONS: The literature provides an inconclusive picture on potential preferred treatments for COVID-19 and their interactions with antineoplastic agents. Future clinical trials are needed to better understand the interactions between different drugs in the context of COVID-19 pandemic.

Increased circulating levels of vascular endothelial growth factor C can predict outcome in resectable gastric cancer patients.

BACKGROUND: Neoangiogenesis has proven to be a relevant pathogenetic mechanism in gastric cancer (GC) and lymphatic spread represents an important well-known prognostic factor. Vascular endothelial growth factor C (VEGF-C) plays a key role in lymphangiogenesis and its blood levels in GC patients are easily measurable. This analysis aimed to investigate the prognostic role of preoperative VEGF-C blood levels. METHODS: VEGF-C serum levels were determined by enzyme-linked immunoadsorbent assay (ELISA) in 186 patients observed at our institution from January 2004 until December 2009 and 82 healthy subjects. Statistical analyses were performed using SPSS 21.0. RESULTS: VEGF-C levels were significantly higher in GC patients (median: 287.4 pg/mL; range, 76.2-865.2 pg/mL) than in the control group (median VEGF-C: 31 pg/mL; range, 12-97 pg/mL). A significant correlation between VEGF-C levels, T, N and tumor stage has been described. The median overall survival (OS) was statistically significantly higher in pts with low serum VEGF-C levels [median: not reached (NR) vs. 26 months; P<0.0001]. Higher preoperative VEGF-C levels correlated also with earlier disease relapse and poor disease-free survival (DFS) (median NR in each subgroup, P=0.005). Furthermore, high VEGF-C levels [hazard ratio (HR) =2.7; P=0.018] and tumor grading (HR =0.44; P=0.007) were independent prognostic factors for OS at multivariate analysis. CONCLUSIONS: Our study showed that increased VEGF-C levels are significantly associated with advanced regional lymph node involvement and poor OS and DFS in pts with resected GC paving the way to a possible application as prognostic factor in the clinical practice.

NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice.

BACKGROUND: Pancreatic adenocarcinoma is an aggressive disease with poor prognosis. In a randomized phase III trial, combination of Nab-paclitaxel (Nab-P) plus gemcitabine showed superior activity and efficacy in first-line treatment compared with gemcitabine alone. METHODS: Nab-P is not dispensed in Italy; however, we obtained this drug from our Ethics Committee for compassionate use. The aim of this study was to evaluate the efficacy and safety profile of this Nab-P and gemcitabine combination in a cohort of patients treated outside clinical trials. From January 2012 to May 2014, we included 41 patients with advanced pancreatic adenocarcinoma receiving combination of 125 mg/m(2) Nab-P and 1 g/m(2) gemcitabine on days 1, 8 and 15 of a 28-day cycle, as first-line treatment. Median age of patients was 67 (range 41-77) years, and 11 patients were aged ≥70 years. RESULTS: Eastern Co-operative Oncology Group performance status was 0 or 1 in 32 patients (78 %) and 2 in nine patients (22 %). Primary tumor was located in the pancreatic head or body/tail in 24 (58.5 %) and 17 (41.5 %) patients, respectively, and nine patients had received biliary stent implantation before starting chemotherapy. Median carbohydrate antigen 19-9 level was 469 U/l (range 17.4-61546 U/l) and 29 patients (70.7 %) had referred pain at the time of diagnosis. Patients received a median six cycles (range 1-14) of treatment. Overall response rate was 36.6 %; median progression-free survival was 6.7 months [(95 % confidence interval (CI) 5.966-8.034), and median overall survival was 10 months (95 % CI 7.864-12.136). Treatment was well tolerated. No grade 4 toxicity was reported. Grade 3 toxicity included neutropenia in 10 patients (24.3 %), thrombocytopenia in five (12 %), anemia in three (7.3 %), diarrhea in four (9.7 %), nausea and vomiting in two (4.9 %), and fatigue in six (14.6 %). Finally, pain control was achieved in 24 of 29 patients (82.3 %) with a performance status improvement of 10 % according to the Karnofsky scale. CONCLUSIONS: Our results confirm that combination of gemcitabine plus Nab-P is effective both in terms of overall response rate, progression-free survival and overall survival, with a good safety profile.

Pancreatic neuroendocrine tumors: Nosography, management and treatment.

Pancreatic neuroendocrine tumors (pNETs) represent about 7% of all NETs, 8.7% of gastroenteropancreatic NETs (GEP-NETs) and 1-2% of all pancreatic neoplasms. In the last two decades, the increased diagnosis of pNETs has generated great interest and the development of different classifications, grading and staging systems. Recently, several trials were performed in order to improve the knowledge of biomarkers and imaging and to provide an early diagnosis, but their role is still under debate. Nowadays, surgery represents the only curative approach for pNETs. Approximately 90% of pNETs are silent and non-functional; therefore, most patients are diagnosed in late stage and present metastatic (60%) or locally unresectable advanced disease (21%) with a poor prognosis. Not many therapeutic options are available for pNETs, with different treatments for G1-G2 and G3 tumors, because these diseases are still rare and trials are made up of few series of patients. At present, medical treatments is controversial. On these bases, we believe that a multidisciplinary team composed of surgeons, oncologists, endocrinologists, radiation oncologists, radiologists, pathologists and medicals nuclear is required. This paper presents a review of present state-of-the-art in the field of pNETs.

Vertebral carcinomatosis eleven years after advanced gastric cancer resection: A case report.

Bone metastasis is an uncommon event in advanced gastric cancer patients and bone metastases are rarely detected as isolated lesions. However, eleven years after treatment for locally advanced gastric cancer, including total gastrectomy followed by adjuvant chemotherapy, a 49-year-old female was admitted to the IX Division of General Surgery of the Second University of Naples (Naples, Italy) exhibiting severe progressive neurological symptoms. Magnetic resonance imaging indicated vertebral abnormalities, with evidence of marrow infiltration in several vertebral bodies; however, a contrast-enhanced computed tomography scan did not detect disease progression to other sites. Biopsy of the soft tissue at the level of the second lumbar vertebra (L2) revealed a metastatic lesion derived from gastric mucinous adenocarcinoma. The patient was initially treated with radiotherapy directed to the L2-L4 vertebral bodies to control the pain. Subsequently, systemic chemotherapy according to a FOLFOX-4 (leucovorin, fluorouracil and oxaliplatin) regimen commenced. However, after eight cycles, pulmonary progression of the disease occurred. Thus, palliative care was administered and the patient succumbed one month later. The late relapse of gastric cancer in the current patient may be associated with the theory of tumour dormancy.

Clinical management of advanced gastric cancer: the role of new molecular drugs.

Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual "scenario" of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice.

Treatment of gastric cancer.

The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4(th) most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status.