ASCO Issues Grudging Nod of Approval for Complementary Cancer Therapies

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When I started seeing headlines that ASCO had “endorsed” certain complementary therapies for breast cancer, I was intrigued. It’s estimated that around half of patients use complementary therapies in their cancer treatment, though I suspect the actual number is higher. We’ll never know for sure because it’s mostly done in secret, as saying the word “curcumin” in an oncologist’s office usually escalates to a mix of deep concern and condescension; you may hear yourself say “vitamin”, but it comes out as “sacrificing sheep to the onc-goddess.” Is this witchcraft coming into the light? I clicked.

“Music therapy.” “Relaxation.” “Yoga.” ASCO concurs that these interventions, as evaluated by the Society for Integrative Oncology and published in their 2017 guidelines, are “safe” for ameliorating side effects in patients undergoing breast cancer treatment. This is no ordinary “safe”, either. While I appreciate the effort to stratify the various complementary modalities based on evidence, which should clarify the vitamin/animal sacrifice distinction, the SIO screened for interventions based on the existence of a confirmatory RCT. These results were then held to an outrageous standard; an “A” rating (i.e, one voodoo doll out of five) meant that there was a “high certainty that the net benefit is substantial”. I don’t think my Tykerb meets that standard. 

The recommended options would likely be reasonable for anyone, in any situation and with any physical limitations. What does music therapy have to do with cancer? If ASCO’s signoff encourages more centers to host yoga classes for patients, I mean, that’s great. If rubber-stamping “meditation” for anxiety makes you feel like you have one more tool available for a distressed patient, again, great. But I’ve never had the impression these types of suggestions and services were controversial.

The controversy is, of course, around oral interventions, especially vitamins and supplements. The guidelines did include some supplements, but due to the RCT requirement, they were extremely limited, both in scope and application. Glutamine is rejected as a nausea/vomiting treatment based on the evidence, but I’d only ever heard of it being used to prevent and treat neuropathy (which is how I used it during paclitaxel), and I guess there was no relevant RCT. The other examples (ginseng for fatigue, soy for hot flashes, ALC for neuropathy) generally weren’t recommended. So that’s settled, right?

But supplements are the complementary modality that patients actually use. This slide was presented at ASCO 2017 by Gary Deng, the head of MSKCC’s integrative medicine service and one of the authors on the recent guidelines endorsement.

I was at that session and will come back to it in a minute. This slide is important for context, because it affirms that you’ve got significantly more people using supplements than anything else. It reflects the overall adult population, but if you surveyed cancer patients, I would guess the distribution of the modalities would stay relatively the same, and only the proportions of participants using the intervention would increase. You’re the same person after you get diagnosed with cancer; you don’t wake up believing in homeopathy the morning after your first PET/CT.

“Natural products” are extremely available, and huge swaths of people take supplements prior to a cancer diagnosis. Vitamin D has been anointed a cure-all; people take iron pills for anemia, vegetarians take B12, Cold-Eeze advertises that the zinc in their lozenges will shorten the duration of a cold, melatonin helps you sleep. The list is endless. We’ve gone through this door. But when you get diagnosed with cancer, you’re supposed to slam it, quickly, or you’re a delusional idiot with a death wish. She just wants hope. She just wants to feel in control. If you take glucosamine, no one says you want “hope” in the war against arthritis. Most people are pragmatists, and it’s not much of a leap to say, Well, I’m already taking astragalus for my allergies; maybe there’s something I can take for my neuropathy. We don’t have an embarrassment of effective conventional solutions for that particular example. Some patients who develop treatment-related neuropathy have it for life. Oh well! (Glucosamine for arthritis pain? Rigorously investigated, publication in the NEJM.)

The complementary therapies talk at ASCO 2017 was part of a bigger session about having difficult conversations with patients, and almost every seat was full. I actually backed away from the door when I arrived to double-check I was in the right room, because it seemed so unlikely that what is often characterized as a rogue, fringe quest that is well outside the domain of the MD was pulling people away from all the IDO talk downstairs (ahh, 2017). But people showed up, and they were attentive and respectful, even accounting for the big laugh Deng got from the comment that most-trafficked page at the MSK website is the (excellent, comprehensive) supplement database.

The presentation was mainly about disarming patients, including rehashing very basic communication skills (don’t say anything obviously judgmental, because people don’t like that; say the patient’s own words back to them; you really have to know where they’re coming from, their upbringing; unearth the TRUE REASON they bought a $10 bottle of milk thistle from the deepest reaches of their troubled souls). It’s hard to rag on somebody for advocating listening, but … it’s not that complicated. Even if we distinguish supplements taken for cancer from all other supplements, the paradigm of cancer treatment favors adding more and more stuff. If you’ve done surgery, chemo, RT, you’re a million percent bought into the idea of a multi-modality approach. There’s potential, if not rigorous human evidence, for all manner of untapped synergy, so why not take on a fourth, fifth, sixth modality? Why not simultaneously? I’m not submitting myself to peer review over here.

Deng assumes, likely correctly, that the average oncologist will have no idea what a patient is talking about when they say “vitamin.” So he suggests redirection as the first response and gives a couple of strategies that represent valid issues: bring up therapeutic dosing levels and bioavailability. Which, sure, these are obstacles to clinical utility. But does that sufficiently resolve the question? If it takes a minimum of 8g of curcumin that is specially formulated to reach a therapeutic concentration, is that so out of reach? There are a bunch of companies that offer enhanced formulations designed to address the absorption issue, and, if you can swallow, eight 1000mg capsules is hardly a deterrent. As Deng says himself, the patient believes this is going to help.

At this point, most patients will nod appreciatively and go home and take the curcumin, maybe the huge dose from a reputable supplement company that attempts a unique formulation so that the curcumin may actually be absorbed – and maybe not.

But let’s say the patient asks again. This is where the talk did impress me. There were three case studies featured, each very different clinical scenarios and cancer types, and one patient did fine on an unnamed supplement protocol after progressing on several lines of chemo and having too low a performance status to attempt another. One out of three was more credit to the dark side than I would’ve expected, and I think some period of stability is pretty good for any intervention, conventional or not, in the 2L+ metastatic setting.

These three case studies were also unique because they represent the rare patients that disclosed their supplement use. That doesn’t often happen, and it’s understandable, because the chance of getting meaningful feedback is low. You might get a, “You do you,” but more likely, you get my personal MSKCC experience: right after I was diagnosed, I asked my assigned oncologist a question about quercetin and intraoperative bleeding risk. We were in a tiny little conference room, during what can only be described as an indoctrination session that could have been titled COMPLIANCE. What was I thinking?

Quercetin, flower therapy, injections of spider venom; I could have said anything, and it wouldn’t have mattered. The response was a talking-to wherein all interventions that didn’t start with “doxorubicin” or “cyclophosphamide” were dismissed as “beet juice” that would cause … I don’t know what, terrible adverse consequences (did I say beets? What is happening?). It was so uncomfortable; if you’ve never heard of quercetin, just say you don’t know. I ended up switching centers before I had to see this person too many more times. Not directly because of the quercetin – which I stopped a few days before surgery and picked up a few days after, surviving to tell the tale – but COMPLIANCE is not the most encouraging theme when you’re 25 years old with an aggressive cancer that was already misdiagnosed once. It also gives a sense of exactly how “integrative” that program was in 2010, though I suspect it’s improved as nearly a decade of patients like me have worn the beet-juice lady down. Even for 2010, though, that reaction was a bit much. There were plenty of supplements in common use in cancer at the time. Melatonin has human data going back to the 90s and almost certainly qualifies as can’t-hurt-might-help, which, in the absence of RCT-quality data, is my bar for supplements. Helps you sleep, may help chemotherapy-induced toxicity, may have some mild cancer inhibitory effects. Three voodoo dolls out of five.

That isn’t to say selecting these combinations is always easy. We know that Velcade and large quantities of green tea (or EGCG) are a no-go, but we don’t have many other hard-and-fast rules. Mixing antioxidants and chemo is contentious; I agonized over it. Pored over the available data, from bench results to rat studies. There’s not much human data to interpret. It kept me up at night, all this second-guessing the use and dose of selenium. I can be somewhat confident that large doses of antioxidants will help protect normal cells (works for rats), but less sure that they won’t also exert protective effects on the cancer cells, or inhibit the functions of the drugs themselves. And if I come to a decision on one particular supplement – is this the answer for all cytotoxics? Just the alkylating agents? This is what patients struggle with. Not whether to do yoga.

Anti-cancer intervention no longer begins and ends in the infusion center, and I appreciate the SIO and these tiny steps to narrow the gulf between “complementary” and “conventional” care. It’s all care, especially when you’re dealing with metastatic disease and the horizon on the patient/doctor relationship is a lot longer. We talk about how novel drugs are converting terminal diagnoses to chronic disease states, and for those patients, quality of life and toxicity is more important than it ever was. If you’re expecting to live five years instead of 18 months with metastatic disease, you support that by preserving your liver or renal function – which could (potentially) be aided by complementary therapies. Oncologists, we know there was no training on this in medical school, and the questions aren’t a test. I see that interpretation a lot, that you’re being tested, that it’s a veiled way of asking, Are you on my side or not? The patient has already chosen to come back for a second, third or fifth time; they trust you. I think the questions are a lot more specific and genuine than that. No one needs oncology to legitimize yoga. That’s been handled, so a token “endorsement” won’t do much to build credibility in an area where patients are genuinely curious and motivated – and have access and resources that are unprecedented. If you don’t want to totally cede authority to the practitioners who offer these therapies and, perhaps more threateningly, the patients themselves, you’ve got to come to play.

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