A recent article published in the cancer journal, The Oncologist, warns that elderly patients and those with cardiovascular disease and hepatic impairment should be treated with extra caution when using 5-HT3 receptor antagonists for symptom relief of chemotherapy and radiation induced nausea and vomiting.

The article, written by Dr. Susan Goodin, Pharm.D and Regina Cunningham, both of the Cancer Institute of New Jersey, says that while 5-HT3's have become the "gold standard" in antiemetic therapy, emerging differences among the agents suggest that the incidence and intensity of adverse reactions requires special attention among healthcare professionals.

Discussing the class of 5-HT3 receptor antagonists, Dr. Goodin said that, "While there are certain pharmacological similarities, there are also pharmacological differences and certainly differences in side effects."

Dr. Goodin's review of the side effect profiles for 5-HT3's included granisetron (Kytril), dolasetron and ondansetron, which have become the agents of choice for preventing acute chemotherapy and radiation induced nausea and vomiting. The article points out that some 5-HT3's are more likely to produce adverse reactions than others.

Ondansetron has been linked to a greater incidence of central nervous system side effects. Also, patients with hepatic impairment taking ondansetron often require dose adjustments. In addition, previous studies have shown the development of ECG changes in healthy subjects from specific 5-HT3 antagonist. The increased QTc intervals seen with the use of dolasetron may indicate a potential for significant cardiac effects in predisposed patients and when given with other drugs that lengthen QT intervals that have been associated with arrhythmias. In fact, the European Agency for the Evaluation of Medicinal Products suggest that all non-cardiac drugs be evaluated further for their potential to induce QTc prolongation.

The available comparative studies of the 5-HT3 receptor antagonists report that ondansetron has a greater effect on ECG intervals compared with granisetron and that dolasetron has a greater effect on ECG intervals compared with ondansetron and granisetron.

"Choosing what we think is a benign agent such as a 5-HT3 antagonist certainly seems inherently sensible," said Dr. Goodin. "But, we may want to think about choosing the one with the least apparent cardiovascular toxicity particularly in susceptible patient populations."

Dr. Goodin states that combination therapy with several chemotherapeutic agents is common in the treatment of patients with cancer. Furthermore, many of these patients -- particularly the elderly -- are likely to be receiving other drugs for comorbid conditions, requiring increased monitoring for side effects.

A report presented at the 2002 International Society of Geriatric Oncology (SIOG) shows that serious coexisting morbidity that negatively impacts a patient's life expectancy were found in 78% of cancer patients over the age of 74 and in 66% of those cancer patients between the ages of 60 and 74.

Dr. Goodin added that many clinical studies exclude certain patient groups, such as those with cardiac disease or renal or hepatic dysfunction. These conditions are more likely to be prevalent in elderly patients with cancer. She said it is therefore imperative that both the individual patient profile as well as the tolerability profile of the proposed treatment be considered when prescribing antiemetic therapy.