الفهرس 
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Abstract
Prostate cancer is the most common non-cutaneous malignancy in men and the second leading cause of cancer morbidity and mortality among men.
ADT is the mainstay and universally accepted first line of treatment in advanced and metastatic cancer prostate; however, ADT is associated with a wide range of adverse effects and reduced quality of life these side effects may compromise OS outcomes
Therefore, new cellular targets and novel molecular therapeutic agents with favorable toxicity profiles are needed. Metformin, a commonly used insulin sensitizer, is a first-line agent for patients with type 2 DM. There is scientific evidence for the antineoplastic effects of metformin and its impact in men with PCa in different disease settings.
In our study we aimed to evaluate the effect of adding metformin to combined androgen-deprivation therapy (ADT) in metastatic hormone naive prostate cancer patients regarding PFS, PSA response as primary endpoint and OS, toxicity profile, and quality of life as the secondary endpoint.
In the present study, we included 132 patients divided into two groups’ median follow-up duration in 36 months; in which there were no differences regarding both demographic and disease features with median age 70 years old in both study groups and median PSA 181ng /ml ranged from 10-998 ng/ml.
In comparison to the control group, metformin treatment led to a significant decline in PSA level, body weight, BMI, and random blood glucose levels towards the end of the study and showed improvement of both PFS (p-value of 0.005) and OS (P-value of 0.003) in the trial arm versus the control arm with more pronounced benefit in patients with visceral metastasis
The results in our study showed that there was also an improvement of time to tumor progression (in the form of biochemical recurrence or distant metastasis) and reduction in mortality with (p-value 0.006); this suggests the positive impact of metformin administration on patients’ outcomes.
Regarding adverse effects in the current study, the trial arm showed a better toxicity profile compared to the control arm in the occurrence of hot flashes, weight gain, and development of edema except for diarrhea and nausea that were common in the metformin group so; metformin was well tolerated, and treatment-related side effects were minimal and easily manageable with better quality of life.
As we know current treatments for PCa result limited because of drug resistance and toxicity that develop over time. Thus, new cellular targets and novel molecular therapeutic agents are needed. In this regard, metformin appears a real candidate more affordable than other expensive therapeutic options: metformin plays a central role as a metabolic homeostasis regulator and indirectly as an antiproliferative and anti-carcinogenic agent.
Overall, metformin may be considered an ideal agent to be used as an adjuvant to standard treatments for PCa, both as monotherapy and combined with chemotherapeutics or other drugs.