New guidelines take aim at chemo-related nausea

Hutch News

New guidelines take aim at chemo-related nausea

Cancer patients ‘should not be vomiting with chemo anymore.’ Can someone please tell Hollywood?

Aug. 24, 2017

Illustration by Kimberly Carney / Fred Hutch News Service

When I found out I had to have chemotherapy following my double mastectomy, I knew what was coming. I’d seen enough movies to know chemo meant three things: hair loss, weight loss and nausea.    

Boy, was I wrong. Not about the hair, of course — that was toast, although I’ve since learned not all chemo takes your hair. But I was way off in the weight loss and nausea department because I was lucky enough to be diagnosed with breast cancer in 2011, 20 years after the introduction of the highly effective anti-nausea drug Zofran.

And I do mean lucky. Before the introduction of this and other powerful antiemetics, going through chemo was incredibly rough. So rough, many patients couldn’t get through a full course of treatment and suffered what is known in oncology circles as a “bad outcome.” In other words, they died. Or wanted to, at least.

Dr. Fred Appelbaum, deputy director and executive director of Fred Hutchinson Cancer Research Center, called anti-nausea drugs an “amazingly important” development in cancer treatment, allowing the bone marrow transplant patients he cared for back in the day to finally tolerate the lifesaving therapies.

Millions of cancer patients have benefited since, present company included.

Writer and breast cancer survivor Diane Mapes

Writer and breast cancer survivor Diane Mapes

Photo by Robert Hood / Fred Hutch News Service

My little Zofran pills — and other drugs like steroids and Ativan that amplify the anti-nausea effect — made it possible for me to get through chemo (and radiation) without throwing up once. Yes, I was queasy and yes, there were close calls, but I never once lost my cookies. Instead, I was able to eat cookies. And chocolate chip banana bread, pancakes and sausage, homemade chicken pot pie, and a host of other comfort foods. I couldn’t eat much of them — or anything other than comfort food — but I got the nutrition I needed and didn’t turn into the scary-skinny cancer patient that haunted my subconscious.

I realize nausea and vomiting is a weird thing to … uh … bring up. But the drugs that shut down this potentially deadly treatment side effect have become a cornerstone of contemporary cancer therapy, a fact that hasn’t quite trickled down to the general public. I was certainly clueless about this; ditto for many others who told me they feared the worst, thanks to Hollywood.

Now, with new guidelines just released by a national oncology panel, cancer patients have even more tools to stem the sickness that can come with treatment.

Published last month in the Journal of Clinical Oncology, the American Society of Clinical Oncology (ASCO) guidelines offer new nausea control medications; tiered recommendations based on each treatment’s emetic risk (or “retch factor,” if you will); information on new combinations of drugs that work even better; a bit of guidance on medical marijuana; and even a cost sheet to help doctors and patients understand the economic impact of it all.

Consider it your emesis nemesis.

'A pillow on the floor of the bathroom’

Fred Hutch’s Dr. Gary Lyman was a member of the panel that produced the new guidelines. A longtime oncologist, public health researcher and national thought leader in patient care, Lyman said he remembers only too well what it was like treating cancer patients before effective anti-nausea meds came on the scene. People would aspirate their vomit and develop pneumonia; they’d become dehydrated and skeletal.  

“It was a travesty,” Lyman said. “Time and again, people with curable cancers would stop their treatment because they just could not tolerate the nausea and vomiting. Their cancer was highly responsive and we knew it could be cured in many cases, but it wasn’t because they didn’t complete their treatment. They simply couldn’t tolerate it.”

Cancer patient Elaine Meddock

Elaine Meddock went through four rounds of chemotherapy without strong antiemetics like Zofran and two rounds with them. The difference, she said, was "night and day."

Photo courtesy of Elaine Meddock

Elaine Meddock, a 56-year-old former state patrol officer from the Oklahoma City area, experienced both sides of the side effect spectrum after she was diagnosed in 1991 with non-Hodgkin lymphoma at the tender age of 29. Meddock had four rounds of the chemo cocktail CHOP (which includes two drugs rated “moderate” on the retch factor scale) without the benefit of today’s anti-nausea drugs.

“I was lucky to get 15 minutes between throwing up,” she said. “You’d get home at 5:30 in the evening and still be up at 4, 5, 6, 7, 8, 9 in the morning. You’d never get to bed, except for a pillow on the floor of the bathroom.”

Meddock said she struggled through with what was available — Benadryl, Compazine and Zantac — but finally reached her breaking point.

“I couldn’t deal with throwing up any more,” she said. “And I was so exhausted. I told the doctor, ‘You’ve got to figure out something else or I’m not taking any more,’ and that’s when he said they’d just come out with a new medication, Zofran. It was only available in IV form and getting it would add an extra two hours to the end of my chemo, but I did it. The last two chemo treatments were a night-and-day difference. I went from vomiting every 15 minutes for 16 hours, to no nausea, just queasiness.”

Nipping nausea in the bud 

Today, there are dozens of drugs to help control nausea and vomiting — not just multiple agents, but multiple classes of agents — and oncologists are advised to give patients the optimal anti-nausea meds, as Lyman put it, “right out of the gate.”

This pre-emptive strike allows patients to control emesis from the get-go and helps avoid “anticipatory” nausea and vomiting, a sort of Pavlovian response where the body learns to associate chemo with throwing up and then has a hard time forgetting it even when strong antiemetics are given.

With better control over a longer period of time, there’s also less chance of “breakthrough” nausea and vomiting when the initial treatments wear off. Providers also have a better understanding of which chemos are the most likely to trigger the brain stem’s vomit center and by how much. Just like not all chemos cause the same amount of hair loss, not all chemos cause the same level of nausea and vomiting.

“Not all chemotherapy is equally toxic,” said Lyman. “You want to give the optimal anti-nausea medication for that particular chemo regimen but not more than they need” to avoid needless side effects without any additional benefit.

To make it easier to figure out the optimal anti-nausea meds for each patient, the new ASCO guidelines break down the chemo drugs into four risk categories:

  • High risk, for chemos like cisplatin and anthracycline/cyclophosphamide combinations that cause emesis more than 90 percent of the time;
  • Moderate risk, for chemos including the common agents doxorubicin (or Adriamycin) and cyclophosphamide (Cytoxan) that make you vomit 30 to 90 percent of the time;
  • Low risk, for chemos that make you sick 10 to 30 percent of the time; and
  • Minimal risk, for drugs that make you throw up less than 10 percent of the time.

There’s also a breakdown for what anti-nausea drugs work best for high, moderate, low and minimal doses of radiation, which can also make patients sick to their stomach.

Dr. Gary Lyman

A longtime oncologist and national thought leader in patient care, Fred Hutch's Dr. Gary Lyman was part of a panel that created new guidelines for antiemetics. These drugs have become a cornerstone of contemporary cancer therapy, allowing patients to better endure their treatment.

Photo by Robert Hood / Fred Hutch News Service

“With rare exceptions, patients should not be vomiting with chemo anymore,” Lyman said. “And you only need a few days of anti-nausea drugs for most regimens. You’re not on them for months at a time, at least early-stage cancer patients aren’t. At most, side effects are very short-lived while you’re getting the chemo or for two or three days after treatment. Late-stage cancer patients may be on them longer, depending on their treatment.”

Anti-nausea drugs also come in different categories: Some work directly on the brain’s vomit center, shutting down the body’s automatic impulse to “clean house” when it detects poison; others help to amplify the effect of other anti-nausea drugs.

Patients, who often receive a mix of drugs known as a “chemo cocktail,” also now receive antiemetic cocktails that might include a steroid (like dexamethasone); a serotonin receptor antagonist (like Zofran); a neurokinin receptor antagonist (like Emend); and maybe even an antipsychotic like olanzapine, which the new guidelines now recommend for patients receiving the highest-risk regimens.

Combos, cannabis and cost

“For low-risk regimens, sometimes a single agent is fine,” Lyman said of these combinations. “But for intermediate or higher risk, it’s important to give anywhere from two to four drugs. They each function at slightly different points either in the vomiting center or within the central nervous system, acting like tranquilizers. They’re hitting it in slightly different directions and the combination of these is more effective than any one by itself.”

Since patients don’t all respond the same way to any one drug, multiple agents in each category give doctors an arsenal to draw from.

“As you can imagine, some patients do a little bit better with one than the other,” said Lyman. “Or they may have fewer side effects with one versus the other.”

Case in point: Amy Goldberg Rowley, diagnosed with breast cancer this last February, had a bad reaction to the Zofran her doctors gave her for her chemo side effects.  

“I ended up with a horrific four-day migraine,” said the 42-year-old from Olympia, Washington. “Chatting with the infusion nurse helped me find Kytril [or granisetron], which is in the same family as Zofran. It worked like a charm.”

While the use of an antipsychotic — in this case, the newly recommended olanzapine — to relieve nausea symptoms in certain patients may sound like a drastic measure, Lyman said antipsychotics have been used in cancer treatment for years.

“We had Thorazine when I was training, in addition to Compazine, a milder version of it,” he said. “Olanzapine is a much more targeted and better tolerated version.”

The ASCO panel creating the recommendations used results from a 2016 Phase 3 randomized controlled trial that found the addition of olanzapine to a standard three-drug anti-nausea cocktail significantly cut back on the patients’ nausea and vomiting. A 2016 statistical analysis of data from multiple studies also showed a benefit.

In other words, the science was there. Such was not the case when it came to the use of medical marijuana to control nausea and vomiting.

For that, the panel made what Lyman called a “murky” recommendation, stating the “evidence remains insufficient” for any kind of endorsement of marijuana, since they don’t have studies that show it’s better than other approved anti-nausea drugs nor do they have studies showing it’s better than the U.S. Food and Drug Administration-approved synthetic cannabinoids dronabinol (aka Marinol) and nabilone (aka Cesamet).

“Marijuana has fallen to the wayside in terms of medical recommendations not because it doesn’t work but because it may not work as well as the other available drugs with fewer side effects,” Lyman said. “We didn’t want to say, ‘Don’t use it,’ but we wanted to say, ‘There’s probably better things out there.’”  

If patients do turn to marijuana for “breakthrough” or “rescue” nausea, the guidelines point to pot pills, rather than pot itself, since there’s no dosing or scheduling information on the various preparations of medical marijuana. Pot, in bud or flower form, may also contain fungal spores that could prove harmful to cancer patients' lungs.

One area where pot may have the other drugs beat, though, is cost.

“It is potentially less devastating financially than some of the newer drugs,” said Lyman, co-director of Fred Hutch’s Hutchinson Institute for Cancer Outcomes Research, which studies ways to reduce the financial burden of cancer care on patients, their families and society.

And the cost of these drugs may be a potential barrier for patients, one reason ASCO’s panel included a table of estimated costs for their recommended antiemetics.

One oral dissolving dose of Zofran, for instance, cost $85 while the generic equivalent, ondansetron, cost $6.50. (Patients often take two or three doses a day over the course of several days.) Members of another class of drugs called NK receptor antagonists, such as the guideline’s newly added rolapitant (or Varubi), sell for more than $600 per single dose.

“If you look at that table, you’ll see there are huge cost differences between name brands and generics,” said Lyman. “They’ve been subject to the same problems we see in cancer drugs in general: out-of-control pricing and price gouging. Doctors don’t always know how much these medicines cost when they prescribe them. We thought it was extremely important to provide the cost information.”

Anyone who’s been through cancer treatment knows the bills alone are enough to cause nausea and vomiting. But I digress. The important takeaway, especially for those who’ve just been diagnosed: Don’t despair or rely on outdated movies for a glimpse of what’s ahead. 

Hollywood may not have caught up with the times, but your oncologist most likely has. If not, feel free to print out a copy of the new ASCO guidelines and bring them with you to your next infusion.

You’ve got nothing to lose, except maybe your lunch.

Diane Mapes is a staff writer at Fred Hutchinson Cancer Research Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she blogs at doublewhammied.com and tweets @double_whammied. Email her at dmapes@fredhutch.org.

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