University of Vermont

Grunberg Presents Study on Oral Anti-Nausea Drug at 2012 European Society of Medical Oncology

Steven Grunberg, M.D.
Professor of Medicine Steven Grunberg, M.D. (Photo by Raj Chawla, UVM Medical Photography)

A study examining the oral formulation of palonosetron, a second generation 5-HT3 receptor antagonist (5-HT3 RA) found the treatment is effective and safe in preventing chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of moderate emetogenic chemotherapy (MEC), according to data presented by University of Vermont Professor of Medicine Steven Grunberg, M.D., at the European Society of Medical Oncology (ESMO) Vienna 2012 Congress held in early October.

CINV is among the most dreaded side effects following therapy in patients with cancer. Despite preventative treatments, on the day of chemotherapy, up to 30 to 45 percent of patients experience nausea or vomiting or require rescue therapy following administration of certain types of emetogenic – or nausea and vomiting-inducing – chemotherapy. Failure to control CINV can result in reduced nutritional status and quality of life. The ability to administer an antiemetic in pill form is more convenient for the patient, and often more cost-effective than intra-venous treatment.

The 5-HT3 receptor plays a pivotal role in the physiological mechanisms involved in nausea and vomiting, and agents that antagonize these receptor subtypes are the basis for control of this effect. Following the development of the first generation 5-HT3 receptor antagonists, such as ondansetron and granisetron, in the late 1980s and early 1990s, in recent years, new compounds, including palonosetron, have been made available for preventing CINV.

“Palonosetron, a pharmacologically distinct 5-HT3 RA, offers superior CINV prevention compared with other 5-HT3 RAs when administered as a single intra-venous dose,” says Grunberg.

Palonosetron is approved by the European Medicine Agency and the U.S. Food and Drug Administration for the prevention of CINV in the intra-venous dosage of 0.25 mg. and in the oral dosage of 0.50 mg. with a demonstrated comparable clinical effect of the two formulations.

“In our multicenter, open-label study, patients received a single 0.75 mg. dose of oral palonosetron to best evaluate the safety of the oral formulation of multiple cycles of chemotherapy,” explains Grunberg.

For the study, a total of 217 patients, enrolled in 22 study centers in Europe, Mexico and the United States, received oral palonosetron with or without – at investigator discretion –  associated administration of dexamethasone (8 mg. on the first day of treatment) one hour prior to MEC for up to a maximum of four consecutive cycles. The total number of evaluated cycles was 654; on average three per patient, with about half of the patients receiving four cycles.

Antiemetic efficacy was maintained across the chemotherapy cycles with overall complete response rates (for example, no vomiting and no need for rescue medication) ranging from 55 to 60 percent of the patients over the three to four cycles.

“The majority of adverse effects were of mild intensity, with headache the most common one,” Grunberg says. “The few severe, serious adverse effects in the safety profile did not raise clinical concerns. In conclusion, we can say that oral palonosetron is well tolerated and effective in preventing CINV over multiple cycles in patients receiving MEC.”

Developed by the Helsinn Group, a privately owned pharmaceutical group with headquarters in Lugano, Switzerland, and operating subsidiaries in Ireland and the United States, palonosetron is marketed as Aloxi®, Onicit®, and Paloxi® in more than 60 countries world-wide.