Search results for "MCI"
showing 10 items of 228 documents
Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer
2017
Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. Methods Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100). Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their…
A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3)
2018
Abstract Background There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. Materials and methods A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2–7, 9–21) were given for 4–6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine…
Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III tr…
2018
Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of …
GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up
2019
Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up. Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled …
NEPA as antiemetic prophylaxis after failure of 5HT3-RA plus dexamethasone in patients receiving carboplatin and gemcitabine chemotherapy: A monocent…
2020
Introduction Chemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients’ quality of life during the therapy. NEPA is an oral fixed combination of netupitant, a highly-selective NK1-RA and palonosetron, a 5HT3-RA, approved for the prevention of acute and delayed CINV. The aim of this study was to evaluate the efficacy and safety of NEPA with dexamethasone for CINV prophylaxis in the challenging setting of carboplatin and gemcitabine combination chemotherapy, after failure of prophylaxis with 5HT3 receptor antagonist. Methods Eligible patients were undergoing carboplatin and gemcitabine combination chemotherapy for metastati…
Gut microbiota and cancer: How gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy
2019
Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors. More recently, accumulating data suggest that the composition of gut microbiota may also affect efficacy and toxicity of cancer immunotherapy. Therefore, the manipulation of gut microbiota through antibiotics, probiotics, prebiotics or fecal transplantation has been investigating with the aim to improve efficacy and mitigate toxicity of anticancer drugs.
Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
2018
In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo. In addition, we demonstrated that autophagy in CAFs c…
Neutrophil to Lymphocyte Ratio as a Predictor of Poor Prognosis in Metastatic Pancreatic Cancer Patients Treated with Nab-Paclitaxel plus Gemcitabine…
2018
Background. High neutrophil to lymphocyte ratio (NLR) has shown to be a predictor of poor outcomes in various malignancies, including pancreatic cancer. Methods. We assessed 70 consecutive pts with histologically confirmed mPC who received chemotherapy with nab-paclitaxel/gemcitabine at two different European oncologic centers between January 2012 and November 2015. Variables assessed for prognostic correlations included age ≥ 66, sex, Karnofsky PS score, primary tumor site, baseline CA19.9 level ≥ 59xULN, 12-week decrease of the CA19.9 level ≥ 50% from baseline, basal bilirubin level, baseline NLR, biliary stent implantation, and liver metastasis. Survival analyses were generated according…
Real life triplet FIr/FOx chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma patients: Recommended schedule for expected activity…
2018
// Gemma Bruera 1, 2 , Silvia Massacese 3 , Stefania Candria 1 , Antonio Galvano 4 , Rosa Manetta 5 , Aldo Victor Giordano 5 , Sergio Carducci 5 , Alessandra Di Sibio 5 , Eugenio Ciacco 3 , Antonio Russo 4 , Enrico Ricevuto 1, 2 and on behalf of Oncology Network ASL1 Abruzzo, Italy 1 Oncology Territorial Care Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Pharmacy Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L’Aquila, Italy 4 Medical Oncology Unit, Department of Surgical, Oncological and Stomatological Sciences, Univers…
Phase Ib study of poly-epitope peptide vaccination to thymidylate synthase (TSPP) and GOLFIG chemo-immunotherapy for treatment of metastatic colorect…
2015
ABSTRACT: Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication and main 5′-fluorouracil (5′-FU) target. TSPP/VAC1 is a multi-arm trial phase-Ib trial program aimed to investigate the toxicity and biomodulatory activity of a poly-epitope-peptide vaccine to TS (TSPP) in cancer patients (pts). Here, we present the results of the TSPP/VAC1/arm C trial aimed to evaluate TSPP in combination with chemo-immunotherapy in pretreated metastatic colo-rectal cancer (mCRC) pts. Twenty-nine pts, 14 males and 15 females, received poly-chemotherapy with gemcitabine [GEM; 1,000 mg/sqm, day-1], oxaliplatin [OX; 80 mg/sqm, day-2], levofolinate [100 mg/sqm, days 1–2], bolus/infusi…