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A New Guide for Using Antiemetics

Author Information (click to view)

Paul J. Hesketh, MD

Director, Thoracic Oncology, Department of Hematology and Oncology

Lahey Clinic Medical Center

Professor of Medicine

Tufts University School of Medicine

Paul J. Hesketh, MD, has indicated to Physician’s Weekly that he has received financial support for his role as a consultant/advisor for Eisai, GlaxoSmithKline, Helsinn, and Merck.

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Paul J. Hesketh, MD (click to view)

Paul J. Hesketh, MD

Director, Thoracic Oncology, Department of Hematology and Oncology

Lahey Clinic Medical Center

Professor of Medicine

Tufts University School of Medicine

Paul J. Hesketh, MD, has indicated to Physician’s Weekly that he has received financial support for his role as a consultant/advisor for Eisai, GlaxoSmithKline, Helsinn, and Merck.

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A significant proportion of all cancer patients experience nausea or vomiting during the course of their treatment. Nausea and vomiting have long been common adverse effects from certain types of cancer therapy and can lead to postponement or refusal of potentially curative treatments in some patients. In addition to reducing quality of life, these side effects often impede patients’ ability to maintain active lifestyles. With the emergence of serotonin receptor antagonists in the early 1990s and, more recently, the NK1 receptor antagonists, there have been steady improvements in the control of nausea and vomiting.

In 1999, the American Society of Clinical Oncology (ASCO) published its first guideline on the use of antiemetic therapies to combat nausea and vomiting in cancer patients. In 2006, the guideline was revised based upon substantial developments, including the introduction of the NK1 receptor antagonists. In 2011, ASCO updated its guideline again to integrate new data that have emerged over the past 5 years (Table 1).

“Clinicians need to communicate with their patients to optimize results.”

“As knowledge about nausea and vomiting has emerged, so too have safe and effective treatments to battle this dreaded complication for patients,” says, Paul J. Hesketh, MD, who served on the steering committee for ASCO’s 2011 guideline. “The new guideline from ASCO emphasizes how the appropriate use of antiemetic therapies can vastly improve a patient’s treatment experience and quality of life by minimizing these side effects. In general, we have more effective and well-tolerated antiemetic agents than ever before. More recently, we’ve learned how to use these agents in more effective ways.”

Reclassifying Risk for Vomiting & Nausea

An important modification offered in ASCO’s 2011 guideline is the reclassification of the risk for vomiting and nausea from a combination using an anthracycline and cyclophosphamide. Both drugs were previously classified as moderate risk for nausea and vomiting. Now, this combination is considered highly emetogenic. “The reclassification of this drug combination regimen is important as it’s often used in patients with breast cancer and non-Hodgkin’s lymphoma,” Dr. Hesketh explains. “The change should trigger physicians to prescribe appropriate antiemetic treatments so that patients can avoid these side effects and reduce their need for treatment delays or dose reductions.”

Drug Recommendations for Vomiting & Nausea

Based upon available clinical data, palonosetron is now the preferred 5-HT3 receptor antagonist for patients receiving moderately emetogenic chemotherapy. The ASCO 2011 guideline recommends that palonosetron be given in conjunction with dexamethasone, a corticosteroid. If palonosetron is unavailable, a first generation 5-HT3 serotonin antagonist may be substituted.

In addition, the guideline provides direction on using fosaprepitant, a relatively new IV formulation of aprepitant. Data demonstrate that fosaprepitant is equivalent to aprepitant in terms of control and prevention of nausea and vomiting. However, fosaprepitant is administered for 1 day—compared to 3 days for aprepitant—to patients undergoing chemotherapy at high risk of vomiting and nausea. Fosaprepitant may be a more convenient or feasible option for patients. These drugs are part of the guideline-recommended “triplet therapy,” which includes an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone.

The 2011 guideline also updates the emetogenic classification of agents administered intravenously by emetic risk (Table 2). “A major goal in cancer care is to personalize therapy to each patient,” says Dr. Hesketh. “The new guideline helps physicians accomplish this goal by stratifying antiemetic needs based on patients’ specific treatments.”

Patient Expectations

In many cases, the severity and impact of nausea and emesis is underestimated. “Some patients may expect nausea and vomiting as normal consequences of treatment, but for most patients, there should be complete control of these adverse events now that we have effective therapies,” Dr. Hesketh says. “Clinicians need to communicate with their patients to optimize results. Patients should be educated upfront on potential side effects of treatment. Maintaining an open dialogue with patients is paramount. Asking patients questions about nausea and vomiting during treatment can cue physicians to seek out treatment to manage the side effects. Tools, such as checklists, may be helpful in assessing such side effects.”

More to Come

Tremendous progress has been made in preventing vomiting, eliminating infection, and managing pain associated with cancer treatment. There is room for further improvement in controlling nausea and vomiting, says Dr. Hesketh. “We still need to conduct clinical research that seeks out more effective approaches to minimizing nausea and vomiting. These adverse events are still some of the most feared side effects of chemotherapy in patients’ eyes. We have more effective and better tolerated antiemetic agents available. The key is to use them in the most appropriate ways possible. This guideline can provide clinicians with evidence-based knowledge so that clinicians can steer their patients clear from these adverse events.”

Readings & Resources (click to view)

Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Onc. 2011 26 Sept [Epub ahead of print].

Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. 2006;24:2932-2947.

Grunberg SM, Chua DT, Maru A, et al. Phase III randomized double-blind study of single-dose fosaprepitant for prevention of cisplatin-induced nausea and vomiting. J Clin Oncol. 2010;28(Suppl):641s.

Herrington JD, Jaskiewicz AD, Song J. Randomized, placebo-controlled, pilot study evaluating aprepitant single dose plus palonosetron and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Cancer. 2008;112:2080-2087.

Hickok JT, Roscoe JA, Morrow GR, et al.  Nausea and emesis remain significant problems of chemotherapy despite prophylaxis with 5-hydroxytryptamine-3 antiemetics: A University of Rochester James P. Wilmot Cancer Center Community Clinical Oncology Program Study of 360 cancer patients treated in the community. Cancer. 2003;97:2880-2886.

Basch E. The missing voice of patients in drug-safety reporting. N Engl J Med. 2010;362:865-869.

 

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