Clinical Trials: Statistical Methods in Drug Combination Studies. W.Zhao and H.Yang (Eds.) (2014). Boca Raton, FL: Chapman & Hall/CRC Press. 224 pages, ISBN 978-1-4822-1674-5.

2017 ◽  
Vol 59 (5) ◽  
pp. 1085-1085
Author(s):  
Tim Holland-Letz
Keyword(s):  
Clinical Trials ◽  
Statistical Methods ◽  
Drug Combination ◽  
Combination Studies

Resveratrol and prostate cancer: the power of phytochemicals

2020 ◽  
Vol 28 ◽  
Author(s):  
Nadia Zaffaroni ◽  
Giovanni L. Beretta
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Antitumor Activity ◽  
Cancer Patients ◽  
Drug Combination ◽  
Natural Compound ◽  
Latency Period ◽  
Chemopreventive Agent ◽  
Long Latency ◽  
Combination Studies

: Prostate cancer is the fifth cause of tumor-related deaths in man worldwide. Due to its long latency period, this pathology represents an ideal type of disease for chemopreventive studies. Among the drugs considered thus far for the treatment of prostate cancer, the natural compound resveratrol emerged as very promising. Resveratrol is a widely recognized as chemopreventive agent and was shown to potentiate the antitumor activity of conventional chemotherapeutics in several tumors, including prostate cancer. Here we overview the literature of the last five years and summarize the recent achievements of resveratrol and its derivatives as antimetastatic agents in prostate cancer. Moreover, drug combination studies as well as nanomedicine approaches proposed to improve resveratrol activity and to overcome delivery drawbacks are addressed. The last part of the review discusses the clinical trials containing resveratrol ongoing on cancer patients.

scholarly journals Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: Why clinical trials have failed and how they could succeed

2020 ◽  
Author(s):  
Madusha Meemanage ◽  
Lindsay C Spender ◽  
Diane Collinson ◽  
Joanna Iannetta ◽  
Pranavi Challapalli ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Drug Combination ◽  
Cytotoxic Chemotherapy ◽  
Randomised Clinical Trials ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Gastroesophageal Cancer ◽  
Combination Studies

Abstract BACKGROUND Oesophageal squamous cell carcinoma (ESCC) has high mortality and poor prognosis. Advanced tumours are treated with fluoropyrimidine/platinum chemotherapy (PBC) followed by second-line irinotecan or taxane monotherapy, but resistance is common and new therapeutic approaches are needed. Approximately 20% of ESCC tumours carry copy number gain (CNG) of the epidermal growth factor receptor (EGFR) gene. Previous analysis of randomised clinical trials shows that anti-EGFR monotherapy benefits biomarker-selected patients with EGFR CNG and/or high expression by Immunohistochemistry (IHC). However, responses are often of short duration indicating that combining anti-EGFR therapy with other agents is required to optimise the benefit from anti-EGFR therapies even in biomarker selected patients. Randomised clinical trials have not shown benefit from the addition of anti-EGFR therapies to platinum fluoropyrimidine chemotherapy and uncertainty remains regarding the optimal cytotoxic chemotherapy partner for anti-EGFR therapies in ESCC. METHODS The effects of EGFR CNG on sensitivity to PBC in a cohort of gastroesophageal cancer patients (n = 302) was evaluated. Drug combination studies using the EGFR inhibitor gefitinib with cytotoxic chemotherapies, docetaxel, cisplatin, oxaliplatin and irinotecan, on cell proliferation and cell death of EGFR CNG ESCC cell lines were assessed. RESULTS EGFR CNG in gastroesophageal cancer patients was associated with better overall survival following platinum-based chemotherapy. Drug combination studies showed that co-administration of gefitinib and platinum-based cytotoxics was frequently antagonistic in cell-based assays in EGFR CNG ESCC, whereas the combination of gefitinib with docetaxel or irinotecan was more efficacious. Co-administration of gefitinib/docetaxel and sequential administration of docetaxel before gefitinib showed synergy, but docetaxel given after gefitinib was antagonistic. CONCLUSIONS Gefitinib/docetaxel co-administration demonstrated synergy and taxanes are likely to provide the most effective cytotoxic chemotherapy partner for anti-EGFR therapies in EGFR CNG-positive advanced ESCC. Combination of gefitinib and platinum-based cytotoxics was antagonistic suggesting anti-EGFR therapies might reduce anti-cancer effects of chemotherapy which could provide a key explanation for the lack of benefit for the addition of anti-EGFR therapies to PBC in randomised clinical trials. Our data suggest that the combination of docetaxel with anti-EGFR therapies, with careful consideration of dosing schedules, should be evaluated in advanced EGFR CNG-positive and/or IHC high EGFR expressing ESCC.

Drug combination studies of PS-1 and quercetin against rhodesain of Trypanosoma brucei rhodesiense

2021 ◽  
pp. 1-5
Author(s):  
Carla Di Chio ◽  
Santo Previti ◽  
Fabiola De Luca ◽  
Alessandro Allegra ◽  
Maria Zappalà ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Drug Combination ◽  
Trypanosoma Brucei Rhodesiense ◽  
Combination Studies

Preclinical evaluation of the ETS inhibitor TK216 against relapsed and refractory childhood leukemia.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10033-10033
Author(s):  
Ritul Sharma ◽  
Satbir Thakur ◽  
Mohit Jain ◽  
Chunfen Zhang ◽  
Anne-Marie Langevin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Drug Combination ◽  
Childhood Leukemia ◽  
Sensitive Cell Line ◽  
Pediatric Leukemia ◽  
Drug Synergy ◽  
Molecular Abnormalities ◽  
Anti Cancer ◽  
Combination Studies

10033 Background: Although survival rates have improved in the recent past, relapse and refractory disease remain a significant cause of death in children with leukemia. This calls for an urgent need for the development of novel therapies that could effectively treat leukemias in children. The E26 transformation specific (ETS) family of transcription factors regulate various normal cellular functions but are abnormally expressed in various cancers, including leukemia. TK216 is an ETS inhibitor, that has shown pre-clinical activity and clinical efficacy in solid tumors. In this study, we explore the feasibility of using TK216 as a therapeutic agent for the treatment of high risk refractory pediatric leukemia. Methods: A panel of pediatric leukemia derived cell lines and primary blast cells representing a spectrum of molecular abnormalities seen in pediatric leukemia were treated in vitro with TK216 to determine cytotoxicity. Normal lymphocytes were used as controls and cell viability was determined 72 hours post-treatment by Alamar blue assay. The induction of tumor cell apoptosis and target modulation were detected by Western blotting. Alterations in the cell cycle were assessed by FACS analysis with PI staining. Drug combination studies were carried out with established anti-leukemic agents to identify synergy for greater therapeutic efficiency. Results: TK216 decreased cell viability in leukemia cells compared to normal lymphocyte controls in a dose-dependent manner with variations in sensitivity noted with inherent molecular abnormalities. The IC50 values observed ranged from 0.22 µM for the most sensitive cell line, MV4-11 to 0.95 µM for least sensitive cell line, SUP-B15. Apoptosis induction upon TK216 treatment was confirmed by PARP cleavage and caspase 3 activation. Cell cycle analysis demonstrated increased sub-G1 population of cells after TK216 treatment. A strong correlation between sub-G1 population and sensitivity of the cell line towards TK216 (47% in MV4-11 vs 3.72% in SUP-B15) was observed. Screening of a panel of 200 FDA approved anti-cancer agents in drug combination studies identified potential agents for drug synergy. Significant drug synergy was noted with TK216 in combination with the epigenetic modifier 5-azacytidine and the Bcl-2 inhibitor, Venetoclax. [Combination Index for Venetoclax and TK216, mean = 0.65 for MV4-11 and 0.33 for SUP-B15]. Conclusions: Data from our study demonstrate that the ETS inhibitor TK216 induces apoptosis and cell cycle arrest in pediatric leukemia cells at physiologically relevant concentrations. Our combination studies identified distinct anti-cancer agents that could be used for developing effective drug combination regimens with TK216. Overall, our findings provide essential preclinical data for the consideration of TK216 in early phase clinical trials for the treatment of selected high-risk and refractory childhood leukemia.

scholarly journals Missing Data in Randomized Clinical Trials for Weight Loss: Scope of the Problem, State of the Field, and Performance of Statistical Methods

PLoS ONE ◽  
2009 ◽  
Vol 4 (8) ◽  
pp. e6624 ◽  
Author(s):  
Mai A. Elobeid ◽  
Miguel A. Padilla ◽  
Theresa McVie ◽  
Olivia Thomas ◽  
David W. Brock ◽  
...  
Keyword(s):  
Weight Loss ◽  
Clinical Trials ◽  
Missing Data ◽  
Statistical Methods ◽  
Randomized Clinical Trials ◽  
And Performance ◽  
State Of The Field
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