The utilisation of acupuncture to manage vasomotor side-effects in prostate cancer patients undergoing androgen deprivation therapy

Reference: August 2024 | Issue 8 | Vol 10 | Page 21

Anti-hormonal treatments are crucial in managing various cancers by targeting hormone-driven growth pathways. In prostate cancer, androgen deprivation therapy (ADT) reduces androgen levels to inhibit cancer progression, while in breast cancer, oestrogen suppression therapies like SERMS (selective oestrogen receptor modulators eg, tamoxifen), aromatase inhibitors like letrozole, or newer oestrogen receptor ‘down regulators’ like fulvestrant are utilised.

In prostate cancer, recent advancements have included the development of next-generation anti-androgens like enzalutamide, which offer improved efficacy over traditional treatments.¹ Anti-hormonal therapies are also applied in endometrial and ovarian cancers where hormone receptor positivity is identified, marking an expanding utilisation in oncology practice.²

The drawbacks of anti-hormonal treatments: Vasomotor side-effects

While anti-hormonal treatments are effective in managing certain hormone receptor positive cancers, they come with a range of side-effects, many of which drastically impact patient quality-of-life and hinder patient compliance with therapy.³ Common side-effects include fatigue, muscle loss, sexual dysfunction, anxiety and depression, osteoporosis, cardiovascular complications, and metabolic changes.⁴

Among these side-effects, vasomotor symptoms such as hot flashes and night sweats are particularly prevalent and bothersome, affecting a significant proportion of patients undergoing hormonal therapies.^5,6,7 Vasomotor symptoms are primarily characterised by sudden feelings of warmth, usually most intense over the face, neck, and chest, often accompanied by sweating or chills. These symptoms can occur several times a day, and in severe cases, they disrupt sleep and daily activities.⁸

The pathophysiology of vasomotor symptoms in patients receiving hormone therapies is believed to involve the hypothalamus, the part of the brain responsible for regulating body temperature. Hormone withdrawal or blockade disrupts the hypothalamic set point for temperature control, resulting in the characteristic side-effects.⁹

The impact of vasomotor symptoms extends beyond physical discomfort. They are associated with significant psychological distress, including anxiety and depression, and can severely impair patient quality-of-life. Moreover, these symptoms can be a major barrier to treatment compliance and can significantly affect cancer patient outcomes.

Patients experiencing severe hot flashes are more likely to discontinue their hormone therapy prematurely, potentially compromising the effectiveness of cancer treatment.¹⁰ In this context, effective management of vasomotor symptoms is crucial for improving treatment tolerability, compliance with treatment, and ensuring optimal clinical outcomes in cancer care.

Anti-hormonal treatment in breast cancer: Developments and vasomotor side-effects

In breast cancer, anti-hormonal therapies are crucial to the treatment of hormone receptor-positive tumours, which constitute about 70 per cent of all breast cancers. These therapies have evolved significantly over the past few decades, with a focus on increasing efficacy while minimising adverse effects. The standard of care typically involves the use of SERMs, such as tamoxifen, which blocks oestrogen receptors, or aromatase inhibitors, like letrozole, which reduce oestrogen levels by inhibiting the enzyme aromatase,¹¹ or more recently, newer drugs like fulvestrant (selective oestrogen receptor degrader) which down-regulate the oestrogen receptor.

While these therapies have proven effective in the treatment of breast cancer, reducing the risk of reoccurrence and improving overall survival, they are not without significant side-effects, particularly vasomotor symptoms. Hot flashes and night sweats are among the most common and distressing side-effects reported by patients on anti-hormonal therapy.¹²

These symptoms are thought to result from oestrogen withdrawal, which disrupts the hypothalamic regulation of body temperature. The severity of vasomotor symptoms can vary, but often result in non-compliance with treatment schedules and in many patients warrant a discontinuation of therapy.¹³ Managing these symptoms is therefore a priority in clinical practice.

Current evidence-based interventions for vasomotor symptoms in breast cancer patients include pharmacologic treatments such as venlafaxine, a serotonin and norepinephrine reuptake inhibitor which has been shown to reduce the frequency and severity of hot flashes in clinical trials.¹⁴

Another option commonly utilised off label by clinicians is gabapentin,¹⁵ which again has significant drawbacks in terms of side-effect profile. Additionally, non-pharmacologic interventions such as cognitive behavioural therapy and lifestyle modifications (eg, avoiding triggers, maintaining a cool environment) can also be beneficial.

As research continues, the development of personalised approaches to managing vasomotor symptoms in breast cancer patients remains a key area of focus.

One promising new treatment for vasomotor side-effects in women is fezolinetant (veozah), a novel non-hormonal treatment which works by selectively inhibiting neurokinin-3 receptors, which is thought to play a crucial role in the regulation of body temperature. Fezolinetant has shown promising results in clinical trials, including the SKYLIGHT 1 study, which demonstrated its efficacy in significantly reducing the frequency and severity of hot flashes in women.

However, it is important to note that the SKYLIGHT 1 study excluded women with breast cancer, which poses a limitation in applying these findings to this population. Despite this, there are anecdotal reports of fezolinetant being used in women with breast cancer to manage hot flashes, often following detailed discussions between patients and their healthcare providers regarding the limitations of the available data.

ADT in prostate cancer: Challenges of vasomotor symptoms

ADT is a cornerstone of treatment for advanced prostate cancer, significantly improving outcomes by reducing androgen levels that fuel prostate cancer growth. Despite its efficacy, ADT is associated with a range of adverse effects that can severely impact quality-of-life, with vasomotor symptoms being particularly challenging. These symptoms, including hot flashes and night sweats, occur in approximately 70-to-80 per cent of men undergoing ADT.¹⁶

Unlike in women, where vasomotor symptoms are more commonly recognised and managed in the context of menopause, there is often a lack of awareness and understanding regarding these symptoms in men, both among patients and healthcare providers.¹⁷ Vasomotor symptoms in men receiving ADT are similarly thought to result from the disruption of hypothalamic thermoregulation due to the sudden drop in testosterone levels.

However, the perception and reporting of these symptoms can be complicated by gender norms and stigma, with some men feeling reluctant to discuss or seek help for what might be perceived as a ‘feminine’ issue.¹⁸ This underreporting can lead to inadequate management of symptoms and contribute to treatment non-compliance.

The impact of vasomotor symptoms in men on ADT extends beyond physical discomfort. These symptoms are associated with significant psychological distress, including irritability, anxiety, and depression, further compounding the challenges of living with prostate cancer.^19,20 Moreover, the chronic sleep disturbances caused by night sweats can lead to fatigue and reduced cognitive function, further diminishing quality-of-life, and likely contributes to poorer outcomes overall.

Given these challenges, it is crucial to recognise and address vasomotor symptoms in men receiving ADT to ensure better treatment adherence and improve overall wellbeing. Recent advancements in ADT, including intermittent androgen deprivation and the use of newer agents such as abiraterone and enzalutamide, offer some hope for reducing the burden of side-effects, but managing vasomotor symptoms remains a critical component of care.²¹

Acupuncture for managing vasomotor symptoms: Mechanisms and evidence

Acupuncture, best known for its central role in traditional Chinese medicine, has been increasingly explored as a complementary treatment for managing vasomotor symptoms associated with hormone therapies. Acupuncture involves the insertion of fine needles into specific points on the body, which are believed to correspond to various physiological processes.

The proposed physiological mechanisms by which acupuncture alleviates vasomotor symptoms include modulation of the autonomic nervous system, resulting in better thermoregulation, and the release of endorphins, which can improve mood and reduce the perception of hot flashes.²² Several studies have investigated the efficacy of acupuncture in managing vasomotor symptoms in women undergoing breast cancer treatment.

A meta-analysis of randomised controlled trials found that acupuncture significantly reduced the frequency and severity of hot flashes, with minimal side-effects compared to pharmacologic interventions.²³

Other studies have demonstrated that acupuncture can improve sleep quality and reduce anxiety, which are common issues associated with vasomotor symptoms.²⁴ This evidence suggests that acupuncture may be a valuable non-pharmacologic option for managing vasomotor symptoms in cancer patients, particularly those who are unable or unwilling to use medication.

Acupuncture in men with prostate cancer undergoing ADT

The application of acupuncture for managing vasomotor symptoms in men undergoing ADT for prostate cancer is a growing area of interest. While the majority of research has focused on women with breast cancer, recent studies have begun to explore the benefits of acupuncture in men experiencing hot flashes as a result of ADT.

A systematic review of the literature indicates that acupuncture can effectively reduce the frequency and severity of hot flashes in this cohort, with some studies reporting a reduction in hot flash frequency by up to 50 per cent for some men.²⁵

Additionally, acupuncture has been shown to improve overall quality-of-life, including better sleep and reduced anxiety.²⁶ These findings are promising, particularly for patients who experience significant side-effects from pharmacologic treatments for hot flashes or who prefer a more natural approach.⁷

Other new developments in the treatment of vasomotor symptoms in men on ADT are ongoing. Venlafaxine has been investigated for its efficacy in managing vasomotor symptoms in men undergoing ADT for prostate cancer. While traditionally used to manage hot flashes in women with breast cancer, venlafaxine has shown promise in reducing the frequency and severity of hot flashes in men on ADT, making it a viable non-hormonal option for those experiencing these distressing symptoms. Despite its benefits, as mentioned, venlafaxine is not without side-effects, which can include nausea, dizziness, and sleep disturbances, leading to variability in patient tolerance and adherence to treatment.²⁷

Recently, a study presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium explored the use of oxybutynin, a medication commonly used for overactive bladder, in managing vasomotor symptoms in men with prostate cancer. The study demonstrated that oxybutynin significantly reduced the frequency of hot flashes and improved overall quality-of-life for patients undergoing ADT.

However, it is important to note that men using newer androgen receptor targeting agents such as apalutamide and darolutamide were excluded from this study due to potential drug-drug interactions. This limitation highlights the need for caution when considering oxybutynin in clinical practice, as these interactions could limit the applicability of this approach for patients receiving advanced androgen receptor therapies.²⁹

Introducing an upcoming multicentre clinical trial of acupuncture in Irish men

In conclusion, the exploration of acupuncture as a treatment for vasomotor symptoms, particularly in men undergoing ADT for prostate cancer, is gaining momentum. Acupuncture offers a promising alternative to conventional therapies, especially for patients who may seek non-pharmacological options to manage these distressing symptoms. The growing body of evidence supporting its efficacy in alleviating vasomotor symptoms in various populations underscores the need for further investigation.

The upcoming VASAPRO trial (Vasomotor Symptom Alleviation through Acupuncture in Patients with Prostate Cancer) is a significant step in this direction. Set to begin in the next few weeks, we will open this multicentre clinical trial at Bon Secours Hospital Cork, conducted in collaboration with Cancer Trials Ireland and University College Cork.

The pilot study will focus on the acceptability and efficacy of acupuncture in Irish men undergoing ADT. The trial’s findings could have important implications, not only for the treatment of vasomotor symptoms but also for the broader integration of acupuncture into oncological care.

As patient enrolment is already active and with ethics approval granted, the VASAPRO study is poised to contribute valuable data that could influence clinical practice. Should the results prove positive, acupuncture may become a more widely recommended option for managing vasomotor symptoms in prostate cancer patients, providing a holistic and patient-centred approach to care.

This trial exemplifies the potential for acupuncture to complement modern medical treatments and improve the quality-of-life for men facing the challenges of prostate cancer.