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.

scholarly journals Preclinical and Clinical Effects of Mistletoe against Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Mohsen Marvibaigi ◽  
Eko Supriyanto ◽  
Neda Amini ◽  
Fadzilah Adibah Abdul Majid ◽  
Saravana Kumar Jaganathan
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Antitumor Activity ◽  
Cancer Patients ◽  
Remission Rate ◽  
Self Regulation ◽  
Herbal Medicines ◽  
Clinical Effects ◽  
Breast Cancer Patients ◽  
Mistletoe Extract

Breast cancer is among the most frequent types of cancer in women worldwide. Current conventional treatment options are accompanied by side effects. Mistletoe is amongst the important herbal medicines traditionally used as complementary remedies. An increasing number of studies have reported anticancer activity of mistletoe extracts on breast cancer cells and animal models. Some recent evidence suggests that cytotoxic activity of mistletoe may be mediated through different mechanisms. These findings provide a good base for clinical trials. Various studies on mistletoe therapy for breast cancer patients revealed similar findings concerning possible benefits on survival time, health-related quality of life (HRQoL), remission rate, and alleviating adverse reactions to conventional therapy. This review provides an overview of the recent findings on preclinical experiments and clinical trials of mistletoe for its cytotoxic and antitumor activity and its effect on HRQoL in breast cancer patients. Moreover, studies investigating molecular and cellular mechanisms underlying antitumor activity of mistletoe are discussed in this paper. The analyzed trials provided evidence that there might be a combination of pharmacological and motivational aspects mediated by the mistletoe extract application which may contribute to the clinical benefit and positive outcome such as improved HRQoL and self-regulation in breast cancer patients.

Knowledge and attitudes regarding clinical trials and willingness to participate among prostate cancer patients

2015 ◽  
Vol 45 ◽  
pp. 443-448 ◽  
Author(s):  
Celia P. Kaplan ◽  
Anna Maria Nápoles ◽  
Steven Narine ◽  
Steven Gregorich ◽  
Jennifer Livaudais-Toman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Willingness To Participate ◽  
Knowledge And Attitudes

Ineligibility of prostate cancer patients in the VA Connecticut Healthcare System (VACHS) to participate in clinical trials due to comorbidities

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5169-5169
Author(s):  
T. M. Mayer ◽  
W. K. Kelly ◽  
J. Concato ◽  
H. Chao
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Healthcare System ◽  
Patient Population ◽  
Performance Status ◽  
Phase Iii ◽  
Medical Conditions ◽  
Eligibility Criteria ◽  
Major Phase

5169 Background: A large proportion of prostate cancer patients receive their care within the VA Healthcare System. As this is a population affected by complex comorbidities, they may be underrepresented in oncology clinical trials. Our objective was to quantify the frequency with which castrate resistant prostate cancer (CRPC) patients in VACHS would be excluded from major phase III randomized controlled trials. Methods: We reviewed records of all prostate cancer patients at the VACHS between 2004–2007 and identified patients with CRPC. We reviewed eligibility criteria of 24 major phase III clinical trials, from 2006 onwards, studying investigational drugs for CRPC and created a “master list” (ML) of the most pertinent criteria. We analyzed our patient population according to both the ML criteria and to the TAX327 study criteria. Results: We identified 106 patients with CRPC, excluded 7 patients with insufficient medical records, and analyzed 99 patients. Performance status and life expectancy could not be accurately assessed from most charts and were excluded as specific criteria (though reflected in other serious medical condition). Major reasons for exclusion according to ML/TAX327 criteria include: 10/10 other malignancy within 5 years; 11/14 abnormal laboratory parameters; 27/30 other serious medical conditions; 3/4 abnormal cardiac function. ML list only exclusions: 5 active angina; 1 unstable DM; 1 major GI surgery; 1 contraindication to steroids. Serious medical conditions included: active cardiac disease, dementia, serious neurologic, psychiatric, vascular, pulmonary or hematologic disease, and poor performance status or compliance. Overall, 45% (45/99) of patients were excluded when using both the ML and TAX327 criteria. Conclusions: Approximately half of CRPC patients in the VACHS between 2004–2007 did not meet eligibility criteria for major therapeutic trials for CRPC. This retrospective review demonstrates that VA patients are underrepresented in randomized clinical trials for CRPC and are a special population due to their complex comorbidities. These findings underscore the importance of designing better clinical trials for CRPC with less barriers for this underrepresented but common patient population. No significant financial relationships to disclose.

Health status in senior adult prostate cancer patients: Limits for active treatment and clinical trials inclusion

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15550-15550
Author(s):  
J. Droz ◽  
G. Albrand ◽  
A. Chaladaj ◽  
A. Fléchon ◽  
C. Terret
Keyword(s):  
Prostate Cancer ◽  
At Risk ◽  
Clinical Trials ◽  
Health Status ◽  
Cancer Patients ◽  
Geriatric Oncology ◽  
Good Health ◽  
Median Number ◽  
Functional Domain ◽  
Careful Clinical Examination

15550 Background: Two-third of patients (pts) with prostate cancer are older than 70 years. Patients are likely to receive active treatments in the curative and palliative settings if they have good health status, moreover they are likely to be offered to participate to clinical trials. Health status evaluation is performed by Comprehensive Geriatric Assessement (CGA). Methods: We have prospectively performed a mini- CGA (Terret C, Expert Rev Anticancer Ther. 2004; 4 : 469–75.) in 69 patients with prostate cancer : 33% pts had localized disease, median age was 78.7 years (68–92). Mini-CGA was based on a careful clinical examination with analysis of physical function, nutritional status (MNA), functional domain (ADL, IADL), cognitive and emotional domains (MMSE, GDS), identification and grading of comorbid conditions (CIRS-G), and a medication review. Social and familial evaluations complete the procedure. Results: Dependancy: only 12% pts are fully independant for ADL and 11% for IADL; 20% pts experienced falls and 32% were at risk of fall. Cognitive functions and depression: 60% pts had normal cognitive funtions, 46% and 4% were moderately and deeply depressed respectively. Nutrition: 22% pts had severe weight loss, 23% were mal nourished and 41% at risk of denutrition. Comorbidities: median CISR-G score was 8 (3–12), 80% and 21% pts had at least one grade 3 and one grade 4 comorbidity respectively. The most frequent comorbidities were by decreasing order of incidence : psychologic, hematologic, endocrine and osteo-articular pathologies. Polymedication: median number of drugs taken by pts was 5 (0–14) and iatrogenicity was observed in 30% pts. A caregiver was identified in 83% pts and 16% pts were living alone. None of the pts were fully independant with no major comorbidity. Conclusions: Health status of prostate cancer patients older than 70 years must be evaluated with the objective to either tailor specific clinical trials or apply adapted standard treatments. Task forces of the International Society of Geriatric Oncology (SIOG) are on the process to establish specific guidelines for prostate cancer treatment in the senior adults and for selection of manageable CGA procedures. [Table: see text]

Clinical fracture associated with androgen deprivation therapy: A retrospective study of early phase clinical trial cohorts.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 234-234
Author(s):  
Zin Myint ◽  
Charles Kunos
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Radiation Therapy ◽  
Adverse Events ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Early Phase ◽  
Performance Status ◽  
Risk Of Fracture ◽  
Common Grade

234 Background: Androgen deprivation therapy (ADT) is the mainstay treatment in both locally advanced and metastatic prostate cancer. Unfortunately, ADT is associated with rapid loss of bone mineral density (a surrogate for fracture risk) within the first 12 months of initial therapy. Methods: A retrospective review of early phase NCI clinical trials from 2006 to 2013 was conducted to assess the risk of fracture for prostate cancer patients treated with ADT. Results: Seven clinical trials of prostate cancer patients who received ADT between 2006 and 2013 were identified. A total of 464 patients were enrolled in the trials. Patient median age was 64 years, the majority were white (90%), and had good performance status. The median baseline prostate specific antigen level was 29.3 ng/ml and the majority of patients had a Gleason score pattern of >7 (71%). Disease was characterized as involving bone only in 43% of patients and multiple sites (bone, node and/or visceral) in 35%. Of 381 patients for which data were available, 36% received prior hormonal therapy, 37% underwent surgical castration, and 16% received radiation therapy. The most common grade 1-2 adverse events reported in the 7 trials were fatigue (36%), followed by hot flashes (27%), anemia (17%) and hyperglycemia (15%). The most common grade >3 adverse events reported were hypertension and hyperglycemia (3% each). Of the total 464 patients, 7 (0.4%) reported having a fracture (5 were baseline and 2 developed while on treatment). Conclusions: Our study reconfirms the association between clinical fracture and ADT exposure; however, the incidence of fracture rate was less than 1%, which was lower than the published population-based cohorts. The difference could be attributed to short-term ADT exposure, and short-duration of follow up. Clinicians should educate patients about risk of fracture with ADT and offer bone health agent earlier in patients at high risk for fracture and also with underlying co-morbidities such as diabetes, poor performance status, chronic steroid use, or undergo radiation therapy.

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