More Focus Needed on Chemotherapy-Induced Nausea as a Cluster of Symptoms

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We need to start thinking about managing the entire cluster of symptoms, not just nausea, otherwise we’re not going to see good results in the near future.
— Alex Molassiotis, RN, PhD

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Management of chemotherapy-induced vomiting has improved with the use of antiemetics, but chemotherapy-induced nausea remains a major clinical problem, according to Alex Molassiotis, RN, PhD, Professor and Head of the School of Nursing at The Hong Kong Polytechnic University. And, he added, the scope of nausea may be broader than we think.

“We often connect it with vomiting, but perhaps there are other issues to consider, and maybe we got it wrong altogether,” admitted Dr. Molassiotis at the 2016 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) International Symposium on Supportive Care in Cancer in Adelaide, Australia.1

Lawrence H. Einhorn, MD, Distinguished Professor of Medicine at Indiana University School of Medicine in Indianapolis, agreed. “I would not say we’ve conquered emesis, but we’ve greatly mitigated the threat of severe vomiting,” he said, adding that the mechanism of nausea is not necessarily similar to the mechanism of emesis in patients receiving chemotherapy. “No longer is the major unmet need for our patients complete remission with no emetic episodes and no use of rescue medication—It is clearly, unequivocally nausea,” declared Dr. Einhorn at the conference.2

No longer is the major unmet need for our patients complete remission with no emetic episodes and no use of rescue medication—It is clearly, unequivocally nausea.
— Lawrence H. Einhorn, MD

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Separating Vomiting From Nausea

“Vomiting is a useful reaction of the body; it protects the body from toxins. We can’t say the same thing about nausea,” said Dr. Molassiotis. “Patients say they feel better after vomiting, but having that constant feeling of nausea really impacts their lives.”

The percentage of patients receiving chemotherapy who experience acute or delayed vomiting is only 20% or less with appropriate use of antiemetics, revealed Dr. Molassiotis, but the percentage of those experiencing nausea is triple that. According to one study, 60% to 70% of patients experienced delayed nausea due to chemotherapy, and the rates of acute and delayed nausea varied according to different chemotherapy cycles.3

Furthermore, a different study showed almost identical results.4 Acute vomiting was observed in 9% to 14% of patients over 2 chemotherapy cycles, but acute nausea was observed in 6 times more patients, 64%. “So linking nausea and vomiting together is probably not the best way to do it,” acknowledged Dr. Molassiotis. “Traditionally, antiemetic trials actually looked at it as a single outcome—chemotherapy-induced nausea and vomiting management—but we need to start splitting these two and looking at them very differently.”

Key Messages From the Literature

According to Dr. Molassiotis, the results of many studies over the years have yielded some key principles regarding chemotherapy-induced nausea and vomiting.

  • Vomiting is largely well controlled, with the exception of moderately emetogenic chemotherapy, where antiemetic management of nausea needs improvement.
  • Nausea, both acute and delayed, is a significant problem in more than half of patients receiving highly or moderately emetogenic chemotherapy.
  • Nausea can be present without vomiting; acute symptoms of chemotherapy-induced nausea and vomiting are better managed than delayed symptoms (of both nausea and vomiting).
  • Some patients receiving highly emetogenic chemotherapy are undertreated, whereas patients in other protocols may be overtreated, especially with low and minimally emetogenic chemotherapy.

Anticipatory nausea is another big problem. A 2016 study showed that every 1-mm increase in anticipatory nausea on the visual analog scale was significantly associated with a 2% to 13% increase in the likelihood of chemotherapy-induced nausea and vomiting.5 “This is important because anticipatory symptoms make a very big difference in the development of [chemotherapy-induced nausea and vomiting] later on,” added Dr. Molassiotis.

Nausea as a Symptom Cluster

“Nausea is very complicated, and patients describe it as various sensations, feelings, and experiences,” Dr. Molassiotis explained. In stark contrast, vomiting is easily described.

In a study of the nausea experience, Dr. Molassiotis and colleagues found that patients used a cognitive process to analyze and make sense of their experience, including its effects on daily life and their eventual acclimatization to nausea.6 The investigators observed patients’ descriptions of nausea and began to consider it as a possible symptom cluster.

“The vast majority of patients who described nausea started describing other symptoms (ie, loss of appetite, taste disturbance, intolerance to smells), and vomiting wasn’t the most common symptom,” explained Dr. Molassiotis. “It wasn’t just about vomiting or just about nausea, as we initially thought.”

From this and a follow-up confirmatory study, they concluded nausea is indeed a symptom cluster that included loss of appetite, dry mouth, drowsiness, and bloating—and to a lesser degree vomiting.7 “Perhaps we need to give it a different name than nausea,” Dr. Molassiotis observed.

A Closer Look at Chemotherapy-Induced Nausea

  • Nausea, not emesis, is the main element of toxicity for chemotherapy-induced nausea and vomiting, and more effort is needed to effectively manage it.
  • Better understanding of the biologic nature of nausea is necessary, but nausea may be broader in scope than initially thought and should be considered more of a symptom cluster.
  • Olanzapine may be the most promising drug for mitigating nausea.

In his subsequent study of 504 patients, followed for 1 year after diagnosis, he and his team found nausea and vomiting were a well-defined system at the beginning of treatment, but by month 12, the clearly defined symptom cluster focused around nausea, with lack of appetite and difficulty swallowing.8

From these and other studies he has led, Dr. Molassiotis concluded that nausea as a symptom cluster impacts physical and functional quality of life as well as nutritional status. “It makes a big difference to look at nausea as a symptom cluster rather than a single symptom,” he summarized.

Management Suggestions

A better understanding of the biologic nature of nausea is necessary, as is a more sophisticated antiemetic prescribing practice and incorporation of newer antiemetics and nonpharmacologic interventions into current antiemetic regimens, Dr. Molassiotis stressed. In addition, he emphasized the effectiveness of nurse-led telephone follow-up and home-care symptom management.9 “Not just for nausea but for a range of symptoms, we saw that educational intervention, supporting patients and giving them some self-management education, actually made a big difference for nausea and also for vomiting.”

Patients should also be educated and prepared for the chemotherapy-induced nausea and vomiting experience. “If patients are well prepared in terms of the symptom experience, they cope better with symptoms than if we just let them go through the experience without any preparation,” stated Dr. Molassiotis. He also said that patients at higher risk should be identified and treated more aggressively.

In terms of pharmacologic options, olanzapine is one of the drugs of choice for managing nausea, according to Dr. Molassiotis. “According to a meta-analysis published this year,10 with vomiting, it makes a little difference, but where it makes a big difference is with nausea,” said Dr. Molassiotis. In fact, a recent randomized phase III trial showed that olanzapine significantly improved nausea prevention in previously untreated patients who were receiving highly emetogenic chemotherapy.11 Dr. Einhorn agreed: “Olanzapine may be the most promising drug for mitigating nausea.”

“Nausea is a major problem, and we haven’t focused enough on it,” concluded Dr. Molassiotis. “We need to start thinking about managing the entire cluster of symptoms, not just nausea, otherwise we’re not going to see good results in the near future.” ■

Disclosure: Drs Molassiotis is an advisory board member of, speaker for, and receives honoraria from Helsinn, Tesaro, Merck, Norgine and has received research grants from Helsinn, Merck, and Acacia Pharma. Dr. Einhorn reported no potential conflicts of interest.


1. Molassiotis A: Nausea and related symptoms. 2016 MASCC/ISOO International Symposium. Session PS09. Presented June 24, 2016.

2. Einhorn L: Introduction to nausea. 2016 MASCC/ISOO International Symposium. Session PS09. Presented June 24, 2016.

3. Molassiotis A, Saunders MP, Valle J, et al: A prospective observational study of chemotherapy-related nausea and vomiting in routine practice in a UK cancer centre. Support Care Cancer 16:201-208, 2008.

4. Farrell C, Brearley SG, Pilling M, Molassiotis A: The impact of chemotherapy-related nausea on patients’ nutritional status, psychological distress and quality of life. Support Care Cancer 21:59-66, 2013.

5. Molassiotis A, Lee PH, Burke TA, et al: Anticipatory nausea, risk factors, and its impact on chemotherapy-induced nausea and vomiting: Results from the Pan European Emesis Registry Study. J Pain Symptom Manage 51:987-993, 2016.

6. Molassiotis A, Stricker CT, Eaby B, et al: Understanding the concept of chemotherapy-related nausea: The patient experience. Eur J Cancer Care (Engl) 17:444-453, 2008.

7. Molassiotis A, Farrell C, Bourne K, et al: An exploratory study to clarify the cluster of symptoms predictive of chemotherapy-related nausea using random forest modeling. J Pain Symptom Manage 44:692-703, 2012.

8. Molassiotis AI, Wengström Y, Kearney N: Symptom cluster patterns during the first year after diagnosis with cancer. J Pain Symptom Manage 39:847-858, 2010.

9. Molassiotis A, Brearley S, Saunders M, et al: Effectiveness of a home care nursing program in the symptom management of patients with colorectal and breast cancer receiving oral chemotherapy: A randomized, controlled trial. J Clin Oncol 27:6191-6198, 2009.

10. Chiu L, Chow R, Popovic M, et al: Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis. Support Care Cancer 24:2381-2392, 2016.

11. Navari RM, Qin R, Ruddy KJ, et al: Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med 375:134-142, 2016.