News Release

Experts highlight cardiovascular and drug interaction risks in elderly patients

Appropriate antiemetic treatment identified as a potential link for reducing patient risk

Peer-Reviewed Publication

Shire Health New York

Boston, MA (September 30, 2002) Delegates attending the 7th International Conference on Geriatric Oncology reviewed data on the special treatment needs of elderly cancer patients. The data is relevant given the increased organ impairment (e.g. increased cardiovascular disease), and the increasing trend for multiple drug consumption ("poly-pharmacy") in the elderly cancer patient. Clinical trial experts say the potential risks to the elderly patient are underestimated due to restrictive clinical trial entry requirements.

Use of granisetron, an antiemetic drug with no cardiovascular restrictions and low potential for drug interactions is an appropriate choice for elderly cancer patients because granisetron is unlikely to create additional complications.

Antiemetics are used to treat chemotherapy and radiation therapy induced nausea and vomiting. Of the antiemetics, the 5HT3 receptor antagonists, like granisetron, are considered the gold standard in treatment and have a good tolerability and safety profile, particularly when compared to the other older antiemetics.

Differences, however, have been noted within the 5HT3 class in relation to the potential for cardiovascular toxicity and potential for adverse drug interactions.

Commenting on the cardiovascular risks from antiemetic therapy, Dr. Matti Aapro (Clinique de Genolier, Genolier, Switzerland) said, "The increased incidence of cardiovascular disease seen with increasing age necessitates careful consideration of the potential cardiotoxic properties of treatments."

"The increased risk from repeat cardiovascular insult in elderly patients with cardiovascular impairment is unknown, but the risk likely exists," said Dr. Aapro regarding clinical implications. "The cardiovascular side effect profile of antiemetics should be a key consideration in the elderly population and clinicians should be selecting the antiemetic with the lowest risk potential," he added.

Granisetron carries no cardiovascular warnings or limitations in patients with cardiac dysfunction. Recent trials have shown that granisetron at doses up to 160 ug/kg in cancer patients (n=51) receiving highly emetogenic chemotherapy had no clinically important effects on ECG, pulse, blood pressure, clinical chemistry and haematology. [1]

Reviewing the risks to elderly oncology patients from poly-pharmacy, Dr. Gridelli (Division of Medical Oncology, Moscati Hospital, Avellino, Italy) reiterated that drug interactions in the elderly could be a significant cause for concern. The risks of drug interactions are due to combination chemotherapy, palliative therapy, co-morbid conditions and patient self-administered therapy, coupled with the added complications of potentially impaired hepatic and renal systems. Physicians should therefore select an antiemetic with low potential for drug interactions so as not to add to this risk.

The 5HT3 class is metabolized by the cytochrome P450 hepatic enzyme system, and consequently co-administration of agents may slow (inhibition) or accelerate (induction) metabolism, which could lead to toxicity or therapeutic failure, respectively. Unlike other antiemetics, granisetron is metabolized exclusively by a single hepatic enzyme family without slowing or accelerating metabolism. Thus, the risk of drug interactions may therefore be less, which should allow physicians to obtain a more predictable drug response.

"The selection of granisetron may simplify patient management in addition to reducing the risk of potential drug interactions," concludes Dr. Aapro.

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