Mindfulness-Based Stress Reduction in the Improvement of Chemotherapy Induced Nausea and Vomiting

chemoPatients undergoing the conventional cancer treatment of chemotherapy often encounter a number of adverse side effects. Cytotoxic drug-induced nausea and emesis (vomiting) are the side effects most feared by cancer patients. The occurrence of chemotherapy-induced nausea and vomiting (CINV) is distressing for patients and may discourage them from continuing with chemotherapy. The incidence of CINV ranges from 30% to greater than 90% within the first 24 hours of initiating moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) (Wickham, 1999). After initial treatment, many patients experience anticipatory nausea and vomiting (ANV) - a state where nausea and/or vomiting occur prior to the next treatment in association with a stress response or increased anxiety conditioned by the physical burden of their primary bout of antineoplastic agent. In terms of prevalence, anticipatory nausea appears to occur in approximately 29% of patients receiving chemotherapy (about one of three patients), while anticipatory vomiting appears to occur in 11% of patients (about one of ten patients) (National Cancer Institute, 2010).  Antiemetics are currently the intervention used in clinical settings to assist patients with prevention and resolution of nausea and vomiting; however, they are not always completely efficacious and possess their own side effects. As such, the need for an additional/replacement intervention void of adverse effects would benefit CINV in patients by relieving symp­toms and ensuring appropriate dosing frequency and amount for improved outcomes.


According to estimates by the American Cancer Society (ACS), there will be over 1.6 million new cancer cases in 2014 resulting in over 585,000 estimated deaths from the disease (Wickham, 1999).  As of 2011, the top 5 cancer sites were as follows:

  • Breast
  • Prostate
  • Lung and Bronchus
  • Colon and Rectum
  • Melanoma of the Skin (National Cancer Institute, 2010).  

In 2007, the latest year for which we have updated sta­tistics, the U.S. incidence rate for all cancers combined was 461 new cases diagnosed for every 100,000 people in the population; the mortality rate was 178 deaths for every 100,000 persons (Wickham, 1999).

Relative survival (5-year) rates for the disease across all sites and among both sexes is currently 66.1%.2 Re­cent statistics indicate that there are currently 14.5 mil­lion cancer survivors; by 2024, there will be almost 19 million cancer survivors (Wickham, 1999). The relative improvement of cancer survival rates is largely dependent upon two factors: 1) improved screening/early detection and 2) advances in interven­tion and treatment.

Although targeted therapies have provided interven­tionists with improved protocols for cancer treatment, a reliance on cytotoxic drugs including various forms of chemotherapy are still prevalent and a necessary component of treatment. Unfortunately, these inter­ventions are accompanied by adverse side effects that often inform the patient’s decision and actions throughout treatment and may result in reduced or delayed dosing.

5-ht-3_mechanism_of_actionWhile a psychosomatic basis for CINV is clear, additional physiological influences also play a role in the onset of symptoms, including afferent stimulation of a chemoreceptor trigger zone (CTZ) or peripheral stimuli from visceral organs and vasculature (via vagal and spinal sympathetic nerves) as a result of exogenous chemicals and endogenous substances that accumulate during inflammation, ischemia, and irritation (Pisters & Kris, 1998; Johnston &Webster, 2009).

Presently, standard clinical intervention for nausea and emesis associated with chemotherapy involves utilization of antiemetic drugs. 5HT-3 antagonists are commonly applied antiemetics in the treatment of CINV that acts on serotonergic receptors found in the central and peripheral nervous systems including chemoreceptor trigger zones (Grunberg, et al., 2004). The serotonin receptors influence various biological and neurological processes such as anxiety, appetite, mood, nausea, sleep, and thermoregulation. As with most antiemetics, 5HT-3 antagonists carries several potential side effects including headache, constipation or diarrhea, fatigue, dry mouth, and transient elevations in liver function tests (Grunberg, et al., 2004). Patients may also receive concomitant administration of Ativan. A benzodiazepine, Ativan works as an anti-anxiety medication.

This study is designed to evaluate the efficacy of mindfulness-based stress reduction techniques in the reduction of chemotherapy-induced nausea and vomiting in patients undergoing cancer treatment in comparison to common standard intervention of the antiemetic drug granisetron with potential co-administration of Ativan (prn).

Background and Significance

CINV and specifically ANV frequently result in dose delays and/or dose reduction. Reducing the optimal dose or delaying treatment during the course of chemotherapy can lead to detrimental consequences including prolonged intervention, reduced probability of relapse-free survival and reduced probability of overall survival (Bonadonna, et al., 1995). (Fig. 1)

Survival Rates

From a nutritional perspective, nourishment is crucial during treatment as it serves to help prevent increased nutrient deficiencies and imbalances which can serve to hamper recovery time. In addition, nutrient status and intake during this juncture aids in physical capacity by reducing fatigue and ameliorating symptoms associated with decreased destruction of red and white blood cells as well as preventing unwanted weight loss and cachexia (Bozzetti, 2013).

Current recommendations for patients undergoing treatment include the following guidelines:

  • Warm, whole and cooked to ease digestion and assimilation
  • Seasonings/herbs to bring out flavor due to loss of taste acuity often experienced during treatment
  • Ensuring adequate protein intake – favoring higher protein macronutrient intake first based on tolerance before consumption of fats and carbohydrates (Bozzetti, 2013).

Mindfulness Based Stress Reduction

meditationIn clinical trials, mindfulness based stress reduction (MBSR) has shown positive benefits to cancer patients in the areas of immune function, mood alteration, and quality of life (Grossman, Niemann, Schmidt, & Walach, 2004; Speca, Carlson, Goodey, & Angen, 2000). In studies with individuals across a range of health parameters, MBSR has demonstrated efficacy in the improvement of depression, anxiety, stress response/resilience, and neuroplasticity - including decreased grey-matter density in the amygdala, which is known to play an important role in anxiety and stress (Grossman, et al., 2004; Hölzel et al., 2011).

Additional studies examining the effects of various mind-body techniques (hypnosis, guided imagery) and yogic breathing have also exhibited an improvement to vagal tone resulting in reduced chemoreflex sensitivity (Brown & Gerbarg, 2005; Mansky & Wallerstedt, 2006). This adaptation to central/peripheral chemoreceptors and vagal effect are physically and emotionally calming.

Research Design and Methods

For this pilot study, participants will be recruited from outpatient cancer therapy centers and clinical treatment locations. Subjects will be preparing for primary chemotherapy and/or radiation therapy but not yet have initiated their first round of treatment. Timing of MBSR intervention may begin 2 weeks prior to first course of treatment to allow practice to become established. Once treatment commences, MBSR session will be scheduled on first day of week before treatment day, with subsequent practice being conducted at patient's convenience based on fatigue and response to treatment, but with goal of following MBSR protocol as closely as possible. Caretakers will be important partners in the active intervention, helping to serve as facilitators and fellow partners in practice.

The study will be randomized utilizing computer allocation concealment and consist of two treatment arms:

  • Treatment Arm 1 (active intervention): patients receiving primary chemotherapy along with standard antiemetic intervention (granisetron and potentially Ativan) and MBSR.
  • Treatment Arm 2 (control group): patients receiving primary chemotherapy along with standard antiemetic intervention (granisetron and potentially Ativan).

MBSR. The active intervention will consist of the structured Mindfulness Based Stress Reduction program originated by Jon Kabat-Zinn and consists of eight weekly group meetings lasting 2.5 h each, plus 1 full day (6.5 h) during week 6 of the course (Kabat-Zinn, 1990). Formal mindfulness training exercises aim at developing the capacity for mindfulness (awareness of present-moment experiences with a compassionate, non-judgmental stance) and include a body scan, mindful yoga, and sitting meditation.

MAT and ESAS Symptom Assessment. Assessment of nausea, vomiting and overall symptom response to the intervention will be derived from use of the MASCC Antiemesis Tool (MAT) developed by the Multinational Association of Supportive Care in Cancer (MASCC) and the The Edmonton Symptom Assessment Scale (ESAS). The ESAS is a nine-item, validated, patient-rated symptom visual analogue scale developed for use in assessing the symptoms of patients receiving palliative care.

Limitations of current MBSR data. Although largely evidence has accumulated on MBSR in the treatment of depression, anxiety and other aspects of cancer symptomatology, exploratory search of PubMed.gov reveals no publication of studies on CINV using MBSR. In addition, a MeSH term for “mindfulness based stress reduction” results in no current heading/item. The MeSH term “mindfulness” exists; however, studies are limited by a lack of standardization which the structured MBSR program can address.

Sample size and effect size considerations. Determination of effect size and sample size for this study will be based on use of Minsize2: a computer program for determining effect size and minimum sample size for statistical significance for univariate, multivariate, and nonparametric tests (Morse, 1999).The study goal will be to provide sufficient sample and effect size to provide statistical significance and warrant additional studies and consideration of the active intervention of MBSR for its potential efficacy in CINV for cancer treatment patients across a broad spectrum of site-specific malignancies.

One benefit related to MBSR as an intervention resides in its low cost. Initial pilot studies attempting to test hypotheses with outcomes that provide statistical significance often encounter challenges with funding due to their cost-prohibitive nature. As an intervention, MBSR avoids this disadvantage. Cost per study subject simply includes the fee for program proctor and materials – a nominal expenditure in comparison to often costly pharmacologic trial interventions.


couple healthyThe study goal is to assess efficacy of MBSR (active intervention) in comparison to current common emetic protocols as it offers a potentially cost-effective adjuvant intervention with excellent safety profile that empowers patients towards enhanced sense of independence and control. This sense of independence and control is critical in patient-centered care and outcomes. The opportunity to bridge the gap between conventional and integrative/complementary models is also promising and lends itself to a trend already popular among cancer-treatment patients who seek complementary interventions to apply in tandem with their standard course of treatment. Validating a well-structured and already well-studied intervention such as MBSR builds confidence in the system and provides patients with more evidence-based options in their own care, recovery and survival.

To view full research poster, click HERE: Research Poster.Bosley-Smith (*note - several elements of the original research design have been updated/modified since creation of the poster and are reflected in the paragraphs above under "Research Design and Methods")



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