Major Advances and Alternative Approaches to Antiemetic Therapy

Nausea and vomiting has been commonly reported by patients ever since chemotherapeutic agents were first used to treat cancer. Advances in pharmacologic control of chemotherapy-induced nausea and vomiting (CINV) have improved the management of symptoms. Still, cancer patients may dread the treatment and its side effects even more than they fear the disease. Chemotherapy-induced nausea and vomiting is often associated with physiologic complications such as fatigue, muscle strain, and metabolic imbalance.[1] Many times it has contributed to inadequate caloric and fluid intake that has aggravated the cachexia often caused by the cancer itself.[1] Poorly controlled CINV may even lead to dose reduction or termination of potentially curative treatment regimens.[2-4]

Clear Overview

The review article written by Lee S. Schwartzberg entitled "Chemotherapy-Induced Nausea and Vomiting: Which Antiemetic for Which Therapy?" presents a clear overview of therapies for treating nausea and emesis and the continued challenges health practitioners face when these antiemetics do not work well. In addition to updating the reader with regard to classification of the emetogenic potential of available chemotherapeutic agents, Dr. Schwartzberg examines current recommendations for both the prevention and treatment of CINV. The concepts he wishes to convey to the reader are supported by straightforward, comprehensive tables adapted from current American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines for emetic risk and preventive drug regimens, and the clinical trials data taken from the literature are presented in clear, easily interpretable figures.

This review also highlights the substantial advances of the first-generation 5-hydroxytryptamine (HT)3 receptor antagonists in controlling nausea and vomiting over earlier antiemetics, such as metoclopramide and the phenothiazines. The major advances of both aprepitant (Emend) and palonosetron (Aloxi) offer cancer patients significant relief from emesis. However, palonosetron is not indicated for multiple-day use in multiple chemotherapy sessions, and aprepitant alone or in combination with dexamethasone, does not seem to control vomiting as well as 5-HT3 receptor antagonists and dexamehasone.

We have witnessed a rebirth of interest in the use of cannabinoids as effective antiemetics. When active cannabinoids were compared to placebo, cannabinoids were proven to be more effective. Well designed clinical trials of cannabinoids and 5-HT3 receptor antagonist-plus-dexamethasone combination therapy are still needed to determine its effectiveness. Despite the introduction of new, more effective antiemetics and increased compliance with antiemetic guidelines, many patients are still experiencing delayed CINV.

Alternative Therapies

Recently, we have seen a noticeable increase in the use of alternative and behavioral treatments of chemotherapy-induced nausea and vomiting. Alternative and behavioral interventions, such as acupuncture/acupressure and progressive muscle relaxation training (PMRT), are noninvasive and lack negative side effects, which has contributed to patients' willingness to use these methods.

Acupuncture has been shown to be effective in the treatment of postoperative and chemotherapy-related nausea and vomiting. In one study, both acupuncture and acupressure were found to be effective for treating chemotherapy-induced nausea and vomiting in adults.[5] An interim analysis of acupuncture against CINV in pediatric patients also showed positive results.[6]

Another alternative intervention, PMRT allows the participant to achieve a state of muscle relaxation in anticipation of, or in response to, a variety of specific situations that may produce tension or anxiety, such as the receipt of chemotherapy. A series of randomized clinical trials have demonstrated the efficacy of relaxation-based behavioral interventions.[7-9] This technique involves actively stretching and then relaxing specific muscle groups in a progressive manner. This method, often combined with guided imagery (in which the individual visualizes pleasant, soothing images), helps the patient achieve a state of relaxation.

PMRT is generally taught to individual patients by a trained therapist, after which the patient practices the technique using either an audiotape made during the training session or a set of written instructions. The ability to achieve a relaxed state after a few therapist-directed sessions greatly enhances the cost-effectiveness of the procedure by limiting therapist involvement, and facilitates its continued effectiveness over time.[10-14]

Conclusions

The clinical review written by Lee Schwartzberg is comprehensive and balanced. Dr. Schwartzberg should be commended for bringing to the forefront the need to improve treatment options for CINV, as well as for reminding us to remain vigilant in our efforts to prevent the condition.

-Colmar Figueroa-Moseley, PHD, MPH
-Gary R. Morrow, PHD, MD

Disclosures:

The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

References:

1. Osoba D, Zee B, Warr D, et al: Effect of postchemotherapy nausea and vomiting on health-related quality of life. The Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group. Support Care Cancer 5:307-313, 1997.

2. Cooper S, Georgiou V: The impact of cytotoxic chemotherapy-perspectives from patients, specialists and nurses.

Eur J Cancer

28A(suppl 1):S36-S38, 1992.

3. Love RR, Leventhal H, Easterling DV, et al: Side effects and emotional distress during cancer chemotherapy.

Cancer

63:604-612, 1989.

4. Stewart DJ: Cancer therapy, vomiting, and antiemetics. Can J Physiol Pharmacol 68:304-313, 1990.

5. Collins KB, Thomas DJ: Acupuncture and acupressure for the management of chemotherapy-induced nausea and vomiting.

J Am Acad Nurse Pract

16:76-80, 2004.

6. Reindl TK, Geilen W, Hartmann R, et al: Acupuncture against chemotherapy-induced nausea and vomiting in pediatric oncology. Interim results of a multicenter crossover study.

Support Care Cancer

14:172-176, 2006.

7. Morrow GR, Morrell C: Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy.

N Engl J Med

307:1476-1480, 1982.

8. Morrow GR, Asbury R, Hammon S, et al: Comparing the effectiveness of behavioral treatment for chemotherapy-induced nausea and vomiting when administered by oncologists, oncology nurses, and clinical psychologists.

Health Psychol

11:250-256, 1992.

9. Yoo HJ, Ahn SH, Kim SB, et al: Efficacy of progressive muscle relaxation training and guided imagery in reducing chemotherapy side effects in patients with breast cancer and in improving their quality of life.

Support Care Cancer

13:826-833, 2005.

10. Burish TG, Lyles JN: Effectiveness of relaxation training in reducing the aversiveness of chemotherapy in the treatment of cancer.

J Behav Ther Exp Psychiatry

10:357-361, 1979.

11. Burish TG, Carey MP, Krozely MG, et al: Conditioned side effects induced by cancer chemotherapy: Prevention through behavioral treatment.

J Consult Clin Psychol

55:42-48, 1987.

12. Lyles JN, Burish TG, Krozely MG, et al: Efficacy of relaxation training and guided imagery in reducing the aversiveness of cancer chemotherapy.

J Consult Clin Psychol

50:509-524, 1982.

13. Morrow GR, Dobkin PL: Anticipatory nausea and vomiting in cancer patients undergoing chemotherapy treatment: Prevalence, etiology, and behavioral interventions.

Clin Psychol Rev

8:517-556, 1988.

14. Spiegel D, Spiegel H: Hypnosis in psychosomatic medicine.

Psychosomatics

21:35-41, 1980.