Second Generation 5-HT3 Antagonists Open New Perspectives in Emesis Prevention

ROME - The MASCC (Multinational Association of Supportive Care in Cancer) 2009 International Symposium opens today in Rome, Italy - Chemotherapy-induced nausea and vomiting (CINV), treatment of pain, and quality of life in survivors among the key topics of the conference

“Supportive care in cancer is a field of increasing relevance for both oncology patients and clinical research”, said Maurizio Tonato, Co-chair of the MASCC 2009 International Symposium, inaugurated in Rome today. Tonato explained how supportive care, in conjunction with anticancer treatments, may significantly increase quality of life in patients especially addressing the most dreaded consequences and complications, including pain and emesis.

“MASCC-Multinational Association of Supportive Care in Cancer, founded in 1990, is an international, multiprofessional organization that encompasses all aspects of cancer care beyond direct antineoplastic approaches”, echoed Fausto Roila, also Co-chair of the Rome MASCC 2009. “Significant advances in cancer treatment in the last two decades have been made possible by the strides in supportive care”, Roila continued.

Chemotherapy-induced nausea and vomiting (CINV) is among the most frequent side effects following therapy in patients with cancer. “Despite prophylaxis on the day of chemotherapy, up to 30-45 percent of patients experience nausea or vomiting or require rescue therapy following administration of certain types of emetogenic chemotherapy”, said Richard Gralla, Vice President Cancer Services, North Shore University Hospital and LIJ Monter Cancer Center, Lake Success, NY, USA.

The 5-HT3 receptor plays a pivotal role in the process of emesis, and agents that antagonise 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 ’80s and early ’90s, in the recent years new compounds have been made available for prevention of CINV, including palonosetron.

“Controversy continues whether there should be a guideline-preferred 5-HT3 antagonist”, said Gralla. “5HT3 antagonists remain the cornerstone of antiemetic regimens for cancer patients receiving emetogenic chemotherapy. Guideline groups indicate that no significant differences in emesis control are found among any of the earlier selective 5HT3 antagonists. But palonosetron has shown superior emesis control over earlier agents in several comparison studies”, he added.

In fact, large trials with palonosetron demonstrated advantages over earlier 5-HT3 agents in preventing emesis with chemotherapy, but these trials used different doses of palonosetron: either 0.25 mg or 0.75 mg per day.

“We conducted an abstracted-data meta-analysis to see if this palonosetron dosings yields differences”, explained Gralla. Eight trials with 1,926 patients included all randomized double-blind studies with these different palonosetron doses - 4 with highly emetogenic and 4 with moderately emetogenic chemotherapy (6 with intravenous and 2 with oral palonosetron). The findings indicated the same results with both palonosetron doses for all important considerations, including all 5 days complete control and delayed emesis, as well as complete control and complete control plus no use of rescue medication. “Palonosetron doses of 0.25 mg or 0.75 mg yield very similar efficacy and safety with both highly and moderately emetogenic chemotherapy in our meta-analysis. And these findings conclude that whichever dose you administer, the efficacy of palonosetron is preserved, and the beneficial results with palonosetron compared with each of the older 5-HT3 receptor antagonists used so far, can be extended to include all studies using either of these palonosetron doses”, he concluded.

About Palonosetron (Aloxi(R), Onicit(R), Paloxi(R))

Palonosetron (palonosetron hydrochloride) is a selective 5-HT3 receptor antagonist, developed for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, with a long half-life of 40 hours and at least 30 times higher receptor binding affinity than currently available compounds. Palonosetron is a second generation 5-HT3 receptor antagonist, and demonstrates, in clinical trials and clinical practice, a unique long-lasting action in the prevention of CINV. The product has shown to be effective in preventing both acute and delayed CINV in patients receiving moderately emetogenic chemotherapies. A single intravenous dose of palonosetron (0.25 mg) provides better protection from CINV than first-generation 5-HT3 receptor antagonists throughout a 5-day post-chemotherapy period. This means that a single administration of palonosetron also grants protection during the delayed phase of CINV.

Palonosetron 0.075 mg IV is also approved by FDA as a single intravenous dose administered immediately before the induction of anaesthesia for the prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery.

Palonosetron is contraindicated in patients known to have hypersensitivity to the drug or any of its components. The most commonly reported adverse reactions (incidence more than or equal to 2 percent) in CINV trials with palonosetron were headache (9 percent) and constipation (5 percent), and they were similar to the comparators. In PONV trials, the most commonly reported adverse reactions were QT prolongation (5 percent), bradycardia (4 percent), headache (3 percent), and constipation (2 percent), similar to placebo.

Palonosetron has been developed by Helsinn Group of Switzerland and today it is marketed as Aloxi(R), Onicit(R), and Paloxi(R) in more than 40 countries world-wide. Palonosetron, marketed as Aloxi(R), is the leading brand in the USA within the CINV Day of Chemo segment, and it is steadily growing in the European markets.

For more information about palonosetron, please visit the website: www.aloxi.com

About Helsinn Group

Helsinn is a privately owned pharmaceutical group with headquarters in Lugano, Switzerland, and subsidiaries in Ireland and USA. Helsinn is the worldwide licensor of palonosetron.

Helsinn’s unique business model is focused on the licensing of pharmaceuticals and medical devices in therapeutic niche areas. The Group in-licenses early stage new chemical entities, completes their development from the performance of pre-clinical/clinical studies and Chemistry, Manufacturing and Control (CMC) development, to the filing for and attainment of their market approval worldwide.

Helsinn’s products are sold directly, through the Group subsidiaries, or eventually out-licensed to its network of local marketing and commercial partners, selected for their deep in-market knowledge and know-how, and assisted and supported with a full range of product and scientific management services, including commercial, regulatory, financial, legal and medical marketing advice.

The active pharmaceutical ingredients and the finished dosage forms are manufactured at Helsinn’s cGMP facilities in Switzerland and Ireland, and supplied worldwide to its customers.

For more information about Helsinn Group, please visit the website: www.helsinn.com

Contact person at Helsinn Healthcare SA: Paolo Ferrari Head of International Marketing Phone: +41-91-985-21-21 E-Mail: info-hhc@helsinn.com

Source: Helsinn Healthcare SA

Contact person at Helsinn Healthcare SA: Paolo Ferrari, Head of International Marketing, Phone: +41-91-985-21-21, E-Mail: info-hhc at helsinn.com