Symptom management for cancer patients has come a long way in the last few decades. Perhaps one of the greatest triumphs has been gaining better control of chemotherapy-induced nausea and vomiting (CINV).
Those of us who have been in oncology a while can remember the days when patients received highly emetogenic therapy and within minutes or hours were retching or vomiting, easily heard around the hospital unit.
Today, with the use of drug classes like the 5-HT3 antagonists (e.g. Zofran, Kytril, Aloxi) and NK-1 antagonist (e.g. Emend), both typically given in combination with corticosteroids (e.g. Dexamethasone), we usually give patients a good fighting chance of not becoming nauseous and/or rarely throwing up. There are, however, those patients that come to mind who seem refractory to all the "big guns" we give.
Remember, CINV is classified into four different sub-types: acute, delayed, anticipatory, or breakthrough. Acute and delayed CINV not only differ in their timing, but also in the physiologic pathways involved. Whereas acute CINV appears mediated by serotonin pathways (thus being responsive to 5-HT3 antagonists), delayed CINV is more mediated by substance P (which is targeted by NK-1 antagonists) (Hawkins, 2009). Anticipatory CINV is a learned behavior that often arises from nausea not well controlled early on or related to environmental stimuli, such as the smell when walking into the chemotherapy infusion area. Traditionally, benzodiazepines (e.g. Ativan) have been helpful with this.
Finally, there is breakthrough CINV, which is seen in those patients, as the name implies, who have nausea "breaking through" despite standard anti-emetic therapy. This last group has always been the most difficult to treat. Medications to use in this setting may include dopamine receptor antagonists such as Reglan or Haldol, with the downside being risk of extrapyramidal side effects. The cannabinoids (e.g. Marinol) offer another option but can sometimes cause mood alteration, distortion of perception, and ataxia. The 5-HT3 antagonists plus corticosteroids are often continued beyond the acute-phase for these patients as well (Hawkins, 2009).
But how about using the atypical antipsychotic Zyprexa? Perhaps some of you have heard of this or have seen it utilized in your practice setting. As I researched, it seems this drug has been used for a few years now, off-label, for breakthrough CINV.
Recently we have gained some new evidence-based knowledge to back up this practice. Results from a phase III study were presented this year at ASCO showing the great benefits of Zyprexa for breakthrough CINV. The 205 chemotherapy-naïve patients were given highly emetogenic chemotherapy and treated with standard CINV medications per standard guidelines. Of these patients, 80 had breakthrough CINV and were randomized to receive either Zyprexa 10mg daily for three days or Reglan 10mg three times a day for three days. They were then monitored by nurses over 72 hours.
Ultimately,
- 71 percent of patients on the Zyprexa arm did not experience vomiting, compared with 32 percent of those receiving Reglan
- 67 percent of Zyprexa patients did not experience nausea, versus 24 percent of the Reglan patients
One very important thing to remember, especially when educating your patients about use of this drug, is that although Zyprexa has many reported potential adverse side effects (e.g. weight gain, dizziness, personality alteration) when used to treat patients for psychosis, those effects are seen after a patient has taken the drug consistently for three to nine months. Significant toxicity was not seen in study patients using it short term for CINV (Shaffer, 2012). The drug still does not have an FDA indication for this specific use, but perhaps studies like these will help to make that a reality.
So what's working for you in practice to treat these refractory CINV patients? Does anyone have complementary therapies with which they've had good success (e.g. acupuncture, ginger)?
References:
- Hawkins, R. (2009). Chemotherapy-induced nausea and vomiting: challenges and opportunities for improved patient outcomes. Clinical Journal of Oncology Nursing, 13(1), 54-64.
- Shaffer, A. (2012). Olanzapine proves effective in breakthrough CINV. ASCO 2012 Continuing Education: Clinical Insights, July/August 2012, 23.
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