Palonosetron for prevention of acute and delayed nausea and vomiting induced by moderately emetogenic adjuvant folfox-4 regimen in colorectal cancer (CRC) patients: A phase II study of the Gruppo Oncologico dell' Italia Meridionale (GOIM)

Introduction: Folfox-4 is the standard adjuvant treatment in stage III colon cancer and is also recommended in high-risk stage II colon cancer. Oxaliplatin-based regimens are considered moderately emetogenic therapies. Palonosetron, a new selective inhibitor of 5-HT3 receptors, in combination with dexhametasone showed a high antiemetic activity in pivotal trials enrolling patients treated with moderately or high emetogenic regimens. Considering these data, the GOIM started a multicentre phase II trial aiming to evaluate the activity and safety of palonosetron plus dexhametasone in patients affected by radically resected colorectal cancer and treated with adjuvant folfox-4. Materials and methods: Patients with stage III or high-risk stage II colorectal cancer and receiving folfox-4 as adjuvant treatment entered into the trial. Informed written consent was required. A single pretreatment dose of palonosetron 0.25 mg (intravenous) i.v. followed by dexamethasone 8 mg i.v. was administered. Nausea and vomiting were evaluated on day I and over the following 4 d, with a patient diary including vomiting episodes, daily nausea and use of rescue medications. The main end-point of the study was the absence of vomiting in the entire period (5 d) at the first cycle. The absence of moderately or severe nausea and vomiting on days 1-5 was the secondary end-point. Adverse events were evaluated according to the NCI-CTC criteria. Results: Eighty-five patients entered into the study and were all evaluable for activity and safety. The absence of vomiting on the study period (days 1-5) was observed in 82 (96.5%) patients: one patient on the 1st and two on the 2nd day experienced mild vomiting. With respect to the secondary end-point, the complete control during the acute phase was 96.5% while during the late phase was 92%. The complete responses during the acute and delayed phases were 99% and 89.5%, respectively. The main side-effects (G1 grade) were: constipation 13%, headache 10%, vertigo and insomnia 2%. Conclusions: Palonosetron is a very active antiemetic drug for the prevention of nausea and vomiting induced by folfox-4 regimen. (C) 2008 Elsevier Ltd. All rights reserved.