Comparison of various common whole pelvic radiotherapy (WPRT) and local radiotherapy (LRT) procedures to treat prostate cancer based on dosimetric parameters and radiobiological models

AbstractAndrogen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

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Design, Synthesis and Biological Evaluation of 1-methyl-1H-pyrazole-5-Carboxamide Derivatives as Novel Anti-Prostate Cancer Agents

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210202162953 ◽

2021 ◽

Vol 21 ◽

Author(s):

Xin Chen ◽

Changqing Xu ◽

Yuxia Li ◽

Xiaoming Duan ◽

Guisen Zhao

Keyword(s):

Prostate Cancer ◽

Cell Line ◽

Specific Antigen ◽

Biological Evaluation ◽

Castration Resistant Prostate Cancer ◽

Design Synthesis ◽

Structural Modifications ◽

Lead Compounds ◽

Castration Resistant ◽

Treat Prostate Cancer

Background: The androgen receptor (AR) signaling functions is a critical driving force for the progression of prostate cancer (PCa) to bring about anti-prostate cancer agents, and AR has been proved to be an effective therapeutic target even for castration-resistant prostate cancer (CRPC). Objective: In order to discover novel anti prostate cancer agents, we performed structural modifications based on the lead compounds T3 and 10e.Methods: A set of 1-methyl- 1H-pyrazole-5-carboxamide derivatives were synthesized and evaluated for their inhibitory activities against both expressions of prostate-specific antigen(PSA) and growth of PCa cell lines. Results: Compound H24 was found to be able to completely block PSA expression at 10 µM, and showed prominent antiproliferative activity in both the LNCaP cell line (GI 50 = 7.73 µM) and PC-3 cell line (GI 50 = 7.07 µM). Conclusions: These preliminary data supported a further evaluation of compound H24 as a potential agent to treat prostate cancer.

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A qualitative study exploring men’s experience of sexual dysfunction as a result of radiotherapy and androgen deprivation therapy to treat prostate cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396920000059 ◽

2020 ◽

pp. 1-4

Author(s):

W. Kinnaird ◽

A. Stewart-Lord

Keyword(s):

Prostate Cancer ◽

Sexual Dysfunction ◽

Qualitative Study ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Post Treatment ◽

Self Perception ◽

Treat Prostate Cancer ◽

Treatment Changes ◽

A Priority

Abstract Aim: Sexual dysfunction is a common side effect of external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) to treat prostate cancer. Men are likely to experience erectile dysfunction, low libido, ejaculatory problems and penile shortening. This qualitative study explored men’s perceptions of sexual dysfunction, including factors such as self-perception, relationships and information and support needs. Methods: Semi-structured interviews were carried out with n = 8 men living 18–30 months after EBRT ± ADT. The interviews were transcribed and thematic analysis was carried out. Results: All men experienced sexual dysfunction following treatment. The main themes arising were: (i) priorities—sexual issues were not a priority when making treatment decisions, (ii) information and support—men described a lack of information and support about sexual dysfunction and (iii) impact—sexual dysfunction impacted on their self-perception and relationships. Findings: Men undergoing EBRT/ADT for prostate cancer may be affected by post-treatment changes in sexual function in a range of ways. This study suggests that they would benefit from early and wide-ranging information and support on sexual dysfunction, even if they do not consider it as a priority. Candid discussions about self-perception and relationships, as well as physical changes, may equip them to cope with post-treatment changes.

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