Management of Cancer Cachexia Guideline

An interview with Dr. Eric Roeland from Massachusetts General Hospital Cancer Center on "Management of Cancer Cachexia: ASCO Guideline." This guideline provides evidence-based recommendations on the clinical management of cancer cachexia in adult patients with advanced cancer. Recommendations are made on both pharmacologic and nutritional interventions. Read the full guideline at www.asco.org/supportive-care-guidelines

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Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one, at podcast.asco.org.

My name is Brittany Harvey, and today I'm speaking with Dr. Eric Roland from Massachusetts General Hospital Cancer Center. Lead author on Management of Cancer Cachexia, ASCO Guideline. Thank you for being here, Dr. Roland.

Well thank you very much.

Before we get into the content of this guideline, I want to note that all conflict of interest disclosure information for the expert panel is available online with the publication of the guideline in the Journal of Clinical Oncology.

Dr. Roland, do you have any conflicts of interest to disclose?

Yes, within the last two years, I've served as a consultant for Asahi Kasei Pharmaceuticals, DIG Consulting, Napo Pharmaceuticals, American Imaging Management, Immuneering Corporation, and Prime Oncology. I've also served on advisory boards for Herron Pharmaceuticals and Vector Oncology. And I serve as a member on the Data Safety Monitoring Boards for Oragenics, Kalyra Pharmaceuticals, and [INAUDIBLE] Life Sciences Pharmaceutical Company.

Thank you. Then first, can you give us a general overview of what this guideline covers?

Sure. We performed a systematic review of the literature regarding available evidence for nutritional and pharmacologic interventions for cancer cachexia. Specifically, we searched PubMed and the Cochrane Library for randomized controlled trials and systematic reviews published between 1966 in 2019. We focused our review on adult patients with advanced or incurable cancer. And given the highly variable nature of cancer cachexia, we specifically evaluated the endpoints of loss of appetite or anorexia, body weight, and lean body mass, or skeletal muscle. Our targeted audience included clinicians as well as patients and caregivers.

Can you provide us with a little background on cancer cachexia?

Yes, first I think it's incredibly important for us to define cancer cachexia, especially given its prevalence in cancer care. Traditionally, cancer cachexia has been defined as a certain amount of weight loss over a defined time period. However, cachexia is much more complicated than weight loss alone. It is a multifactorial syndrome characterized by loss of appetite, weight, and skeletal muscle, which leads to fatigue, functional impairment, increased treatment related toxicity, poor quality of life, and even reduced survival. And as clinicians, we need to try to identify any reversible causes contributing to cachexia and treat them. This of course, includes treating the underlying cancer when possible.

Additionally, it's essential for patients to receive optimal palliation of all symptoms that may be interfering with the intake of calories, such as pain, nausea, vomiting, constipation, diarrhea, and depression. Therefore, as clinicians, we need to work in teams of experts that might include expertise in pain, palliative care, nutrition, physical occupational therapy, and mental health where available.

We also need to introduce and discuss the term, cachexia, with our patients and their caregivers, who often have never heard of it before. They may not understand that this term is unique and very different from weight loss alone. I personally have found that describing the unique nature of cachexia and providing the information to patients and caregivers can be very helpful.

Additionally, we need to recognize that food is a very complicated issue. And when we engage patients and caregivers around issues of food, we need to recognize that there are informational needs, but there are also emotional needs. And as clinicians, we help patients and caregivers gain access to evidence based information and interventions, but we equally need to ensure that they receive emotional support. Food represents hope and control in an uncontrollable situation. And not being able to eat or feed a loved one can cause severe distress.

Therefore, we need to engage patients and caregivers regarding these emotional issues and make sure they feel heard. We can also reach out to our mental health colleagues, such as social workers and psychologists, who may help us support patients and caregivers in this difficult issue.

Then, what are the key recommendations covered in this guideline?

With regard to our systematic review, we identified 20 systematic reviews and 13 additional randomized controlled trials. And from this data, we made the following recommendations. First, we found limited data supporting the integration of dietary counseling with or without oral nutritional supplements. However, given the lack of harm and the critical role of educating patients and caregivers, we felt it was important to support referring patients with incurable cancer and loss of appetite and/or body weight to registered dietitian for assessment and counseling.

It's critical for patients and caregivers to learn about practical and safe approaches to feeding. Specifically, registered dietitians may help develop strategies, such as shifting away from three larger meals per day towards frequent high protein, high calorie, nutrient dense snacks. Dietitians can also address questions regarding specific diets, including fad diets and unproven or extreme diets.

Moreover, clinicians should not routinely offer enteral tube feeding or parenteral nutrition to manage cachexia in patients with incurable cancer. A short term trial of parenteral nutrition may be offered to a very select group of patients, such as patients with a reversible bowel obstruction, or short gut, or issues with malabsorption, but otherwise reasonably fit. We also can consider discontinuing previously initiated enteral parenteral nutrition near the end of life, as it is associated with net harm at that time.

With regard to pharmacologic interventions, there are no FDA approved drugs to treat cancer cachexia. Yet there is sufficient data to support two pharmacologic interventions associated with improvements in appetite and/or body weight. And these include progesterone analogs, such as megestrol acetate and corticosteroids. The optimal dose and timing of each drug remains unknown.

Regarding megestrol acetate, data support its role in improving appetite, modest weight gain, and improvement in quality of life. However, the weight gain associated with megestrol acetate is primarily fat and not skeletal muscle. We also need to be aware of side effects of megestrol acetate, including an increased risk of thromboembolic events, edema, adrenal insufficiency, and even an increased risk of death.

As for corticosteroids, the first published double-blind randomized study dates back all the way to 1974, which showed an improvement in appetite and sense of well-being. However, clinicians are aware of the multiple side effects associated with corticosteroid use, that often limit initiation and timing of their use. Additionally, the weight gain associated with corticosteroids is not skeletal muscle.

As important as it is to know what drugs are evidence based, it is also important to note what pharmacologic approaches are not supported by evidence. There are many agents that have been evaluated in clinical trials without any evidence to support an improvement in cancer cachexia outcomes.

One such drug that frequently is asked about is dronabinol or the general class of cannabinoids. Insufficient data was available to recommend dronabinol or medical cannabis, and they have notable side effects, including altered mental status and a higher risk of falls. Especially in the elderly.

Why is this guideline important? And how will it impact practice?

Cachexia is a very common clinical entity and causes lots of distress for patients and caregivers. Oftentimes, the issues regarding nutrition and weight loss can be the central focus of clinical appointments and conversations with oncologists. We need to ensure that patients and caregivers have access to evidence based information and recognize that some interventions may be associated with more harm than benefit.

And finally, you've just spoken to this a bit, but how will these guideline recommendations affect patients?

Primarily, I think these cancer cachexia guidelines will serve as a great educational resource. They will also allow patients to better understand the risks associated with some of the pharmacologic interventions. I also think it's critical to define the current state of evidence in cancer cachexia, as we have many new exciting clinical trials evaluating novel agents in the setting.

Furthermore, as a cancer community, we need to ensure that interventional trials are focused on clinically meaningful endpoints, such as improvements in appetite, muscle mass, and quality of life. We also need to encourage a rigorous but expedited approval of these agents, given the lack of any FDA approved drugs in this setting.

Lastly, we need to recognize this is a multi-modal syndrome that requires the help and expertise of our interdisciplinary colleagues. Supporting our patients and their caregivers with this very difficult syndrome requires as much help as possible.

Great. Thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Roland.

Thank you so much, Brittany. I would also like to recognize and thank ASCO for its support of these guidelines, the talented ASCO staff, and the experts who contributed. Most of all, I'd like to recognize our patients and their caregivers.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-cancer-guidelines.

This guideline also has a companion, cancer.net podcast episode. Cancer.net is the patient information website of ASCO. And we encourage you to learn more by tuning into their episode. You can find their podcast and all ASCO podcasts at podcast.asco.org. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe, so you never miss an episode.