Pietras Presents Pillars of Palliative Care in Ovarian Cancer

Christopher J. Pietras, MD

There are not many randomized placebo-controlled trials investigating the use of ketamine as a palliative agent in ovarian cancer, but Christopher J. Pietras, MD, said that it can be considered in certain patients with difficult-to-treat pain symptoms. This adds to the overall message that palliative care agents should be tailored depending on patients’ symptoms.

“Treating patients’ symptoms, just like treating peoples’ cancers, is very individualized,” said Pietras. “It’s very important to involve the oncologist, the primary care physician, or a specialist in palliative care or pain so that they can assess where the symptoms are coming from and why.”

OncLive: What did you discuss in your presentation on palliative care in ovarian cancer?

What are the elements of palliative care?

What medications are used to manage difficult-to-control symptoms?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Ovarian Cancer, Pietras, who is the director, Palliative Care and assistant clinical professor, University of California, Los Angeles School of Medicine, discussed the elements of palliative care for patients with ovarian cancer.Pietras: I covered end-of-life discussions and their associations with the quality of medical care, as well as their effects on caregivers and family members. Secondly, I focused on difficult-to-control symptoms and the use of ketamine for those symptoms in patients with advanced cancer. Thirdly, I spoke about the importance of treating constipation, which is a common symptom. I also discussed the use of docusate sodium for patients near the end of their lives.Palliative care is specialized interdisciplinary care that is focused on improving the quality of life (QOL) of patients and their families. Palliative care also provides support and direction in the setting of complex medical decision making.For severe pain, first-line agents include opioid medications, such as morphine. If those are ineffective, other types of medications are added. Different possibilities include gabapentin and tricyclic antidepressants such as nortriptyline or amitriptyline. [These agents can be used] for neuropathic-like pain that may result from a cancer that may be touching a nerve.

If those medications are ineffective at high doses, ketamine can be considered in certain populations. Although the data for ketamine do not include a large number of placebo-controlled trials, there are smaller studies suggesting that ketamine may be beneficial when used appropriately for patients with very difficult-to-control pain symptoms. These patients would already be on very high doses of opioids and non-opioid adjuvant medicines, like gabapentin.

Ketamine can significantly improve pain scores in up to half of patients, although we still need to do larger studies and prospective trials to confirm whether these data are correct or not. Part of the presentation addressed that only 3 out of 200 papers, analyzed in the only systemic review we have, met the criteria for generalizable evidence.

Based on that evidence, we have to conclude that we do not yet know whether ketamine will result in symptom improvement. Therefore, ketamine should only be used in a select group of patients who have uncontrollable pain—despite highly escalated opioids and other medications—and in patients who do not have traits that would make them more likely to have side effects. This includes patients who might feel confused and those who have anxiety, as those are the most common side effects with ketamine.

Is there a certain agent that provides the most relief to patients?

Is a patient’s treatment discontinued once they enter palliative care?

Are there specific palliative agents for ovarian cancer as opposed to other gynecologic cancers?

It is also important not to increase the dose too high too quickly because hallucinations are often seen at high doses. We need to start at low doses and slowly increase—generally in the range of once daily—to see if we can get a beneficial effect. It could be that up to half of patients have improvement in symptoms with cautious dose escalation.There’s not a specific agent that works for all people. [Physicians can discern whether it’s] something as simple as sleeping wrong, or a cancer that is causing pressure in a nerve that needs to be treated in a specific way. The treatment needs to be matched to both the disease and the patient’s goals. No matter what plan of care we devise, it should always be based on the values and goals of the patient.If someone was receiving a treatment for their cancer, and we know it’s either working or we’re waiting to see if it’s working, there is no reason to stop treatment. That is unless it was directed by the oncologist in discussion with the patient. Palliative care can involve treating symptoms like pain and nausea and providing support to a patient and family while receiving curative intent therapy. We can help when decisions become more complex. [We can help patients] decide between different chemotherapies or when to stop chemotherapy, but it would not be stopped as a result of palliative care.Pain treatments are not very specific to the disease process. If a mass becomes very large and the bowels are not moving well, which results in cramping pain, we may treat that symptom differently than if the pain results from pressure and inflammation on the edge of the lung.

Are there any ongoing or planned clinical trials in the palliative care setting?

In one case, we would try to decrease the inflammation and keep their bowels loose. If someone experiences pressure on the lung, we might use a medication like a steroid to decrease that inflammation. We are always looking for things other than opioids to decrease any kind of side effects [that may manifest at higher doses].Although these are tough conversations, it’s important to know what patients want so that we can match treatments to their goals. That way we can also lessen a caregiver’s depression and anxiety. We need to know if it’s better to have these conversations early or later in the disease course and what the effect on QOL is.

Is there anything else you would like to emphasize?

The same thing [holds true for] ketamine. There were very few randomized controlled studies of it, especially in patients with advanced [ovarian] cancer. I would like to see trials looking specifically at ketamine compared with placebos in larger populations of patients with very difficult-to-treat pain on high doses of opioids.The most important thing about palliative care is being able to assess what is most important to patients, whether that is done by a specialist in palliative care or by an oncologist. It’s essential that we know what is important to them and how their symptoms affect their life, so they can receive the treatments that best match their goals.