SAN FRANCISCO — „So let me know if you’ve ever seen a patient like this: 70-year-old guy, metastatic lung cancer, who’s using oxycodone. He’s using long-acting morphine for breathlessness and bone pain. He’s going to be starting chemo and immunotherapy soon. And, usually right as you’re walking out the door, he says, 'Doc, should I be using that CBD [cannabidiol] that’s advertised everywhere?'
„So what do you tell such a patient? Do you feel equipped to answer this question?”
These were the questions posed by Daniel Bowles, MD, an associate professor of medicine-medical oncology at the University of Colorado, Boulder.
He was speaking here at the Supportive Care in Oncology Symposium (SCOS) 2019 during a special session on cannabis use.
„We’re talking about this here because oncologists talk about this all the time,” said Bowles.
He highlighted a survey published last year in the Journal of Clinical Oncology that showed that 80% of oncologists reported that they discussed cannabis use with their patients. Half had recommended it to their patients for „some reason or another, but only 30% felt comfortable talking about it,” he commented.
That survey showed that about a third of oncologists think that cannabis is as effective or more effective than standard therapies, and about two thirds of medical oncologists felt that it was a successful adjunct to the medications that patients were already receiving.
The survey also found that cannabis was being recommended for a wide range of symptoms, including poor appetite, nausea, vomiting, anxiety, depression, and coping problems. Overall, cannabis was believed to be as effective or more effective than current therapies. For example, when used for poor appetite/cachexia, 64.5% of oncologists felt cannabis was more effective, 8% thought it was less effective, and 27.6% were unsure.
Bowles also highlighted a study published last year in the European Journal of Internal Medicine, which was reported at the time by Medscape Medical News, that surveyed nearly 3000 cancer patients in Israel. The researchers found that 70% of patients said that cannabis helped with sleep problems, more than half reported that it helped with fatigue, nausea, and vomiting, and about 75% said it helped with anxiety. Additionally, about a third of patients reported that cannabis was useful in decreasing their use of opioids.
Bowles noted that this was a retrospective study, so confounders have to be accounted for. „There could be a placebo effect to this,” he said. „These are people who’ve been selected for using opiates,” he pointed out.
Less Opiate Use?
Cannabis use may potentiate the effect of opiates, Bowles commented. „And maybe that’s what helps decrease our opiate needs in some situations, vs it being just a different way of attacking a pain, and so you have better pain control.”
„There are some anecdotal and population-based studies looking at opiate prescriptions overall in states that have legalized marijuana to some degree or another. And there is a correlation with the introduction of marijuana legalization laws and decreased opiate usage,” he said.
There is a correlation, but not causation. „I think there are lots of other things that could play into this, but it is an interesting signal that I think needs to be followed up on,” he said.
New Data From Clinical Trial
At the same session, new data from a small clinical trial showed that cannabis use led to improved pain control and a reduction in the use of opioids.
These data were presented by Dylan Zylla, MD, medical oncologist and hematologist at the Park Nicollet Foundation, HealthPartners Institute, Minneapolis, Minnesota.
This study was conducted in 30 patients with stage IV cancer who required opioids. In the study, patients were randomly assigned to receive either early cannabis use or later use (control).
The study was structured as a „sort of a randomization to early vs delayed,” said Zylla. „The early group got cannabis for 3 months right off the bat, and the delayed group served as our standard-of-care or control group. This control group was 'enticed' to remain in the study and be randomized, because they would receive cannabis as the study progressed.
„Part of the problem with this study is we had a pretty high dropout rate,” Zylla said. „A lot of people, especially in the delayed-cannabis arm, ended up going to hospice or dying, actually even in the first 3 months of the study. Unfortunately, we also had a lot of insufficient data.”
Overall, the results showed that patients who received cannabis at the start of the study did not require opioid dose escalation. Their mean pain score was lower than that of patients in the control group, and their quality-of-life scores were similar to the control group’s, Zylla reported.
At 3 months, the mean pain score, measured on a scale of 0 to 10, declined in patients in the early group from 5.3 to 4.7, whereas it remained the same, at 6.1 to 6, among control patients.
Likewise, the mean personalized pain goal dropped 3.4 to 3.0 in the early group, vs 4.1 to 3.8 for the control patients. The percentage of patients who met that goal rose from 25% to 44% in the early-use group but declined among control patients from 38% to 13%.
Importantly, opioid use remained stable in the early-cannabis group. The mean daily oral morphine equivalent (OME) was 55 at baseline and 54 at 3 months, whereas in the control group, it rose from 35 to 67.
„Forty-four percent of patients [in the early-use group] had a 20% reduction in their OME at 3 months, vs zero [in the late-use group],” said Zylla.
By the end of the 6-month study period, nearly half of the patients (47%) in the delayed-cannabis group had died, compared to only 20% in the early-cannabis arm.
„I think there are some potentially important things here in terms of the results,” Zylla commented. „The optimist in me might say that patients who received cannabis 3 months earlier were doing better,” he continued. „They were able to tolerate their treatments better, get through things better, and were feeling better overall, ” he noted.
„Who knows? Maybe there’s a magical anticancer benefit of the cannabis,” he said, half jokingly, „but it’s far too early to say that.”
The take-away message is that cannabis was generally well tolerated in this study. It may have led to improved pain control, as well as improvement in other symptoms, and it may have lowered opiate requirements, Zylla commented. „And so somebody just like you, who treats these patients with these symptoms ― you’ve got a medicine for pain, you’ve got a medicine for nausea, for anxiety, for insomnia, for all these things,” he said. „And cannabis is that one medicine that might do all of those things and do it in a relatively safe way.”
But the caveat is that „we don’t really know how to use it,” he emphasized.
„We don’t have the data to guide us on dosing, or products, or types, and that’s where further research like this is needed.”
Zylla and his team have several studies in development, a few of which have already received funding. They are hoping to launch in early 2020.
A Few More Points
Bowles pointed out a few more issues that oncologists should be aware of when talking about cannabis with their patients. One is that there are different ways of ingesting cannabis — it can be smoked, vaped, or received as edibles or tinctures. The onset and duration of the effect will vary, depending on the method used, so it is important for oncologists to ask patients what type of product they are using, he said.
Dosage is also important, but it can be difficult „to exactly know what is the right therapeutic dose, both in terms of efficacy but also in terms of concerns for toxicity,” Bowles noted. He emphasized that in „real life,” this can be confusing and intimidating for patients. It is also difficult to find out how much a patient is using in terms of milligrams of CBD and THC, the two primary components.
Cannabinoids interact pharmacologically with other agents, but the clinical importance of these interactions is not yet clear, Bowles commented.
There is also evidence that cannabis may interfere with immunotherapy. Some research has suggested that for patients with melanomas, kidney cancers, and lung cancers, use of cannabis is associated with lower response rates. But this finding did not correlate with overall survival or progression-free survival, he noted.
„I don’t think we can say anything definitive based upon this, but you can make an argument,” Bowles said. „Cannabinoids have anti-inflammatory properties, and we avoid other anti-inflammatory drugs when people are on these agents, so you can spin a little bit of a yarn that maybe this is important.”
In his practice, he does bring this point up with patients who are receiving immunotherapies, telling them that „we just don’t know in this situation. If there are other agents that work as well to control your symptoms, maybe we should be trying those instead.”
Summarizing, Bowles said that his take-home message for oncologists is, as a general rule of thumb, to use the lowest effective dose possible and then titrate up slowly. „Listen to reports of side effects and be aware of what the rules are in your own state, because different states are more rigorous than others in terms of how products are processed, validated, etc,” he said. „And then do beware of drug interactions.
„I think, more than anything, if we’re going to use this like a medication, we should use it like a medication, knowing that it’s not nearly as tightly controlled as many of our other agents,” he concluded.
The study was funded by the Park Nicollet Foundation and the HealthPartners Institute. Zylla had received research funding from Amgen (inst), AstraZeneca (inst), Celegene (inst), Exact Sciences (inst), Innate (inst), Novartis (inst), and Roche (inst). Several coauthors have also disclosed relationships with industry. Bowles has disclosed relationships with Bristol-Myers Squibb.
Supportive Care in Oncology Symposium (SCOS) 2019: Abstract 109, presented October 25, 2019.