Maemondo, M., Masuda, N., Sekine, I., Kubota, K., Segawa, Y., Shibuya, M., … PALO Japanese Cooperative Study Group. (2009). A phase II study of palonosetron combined with dexamethasone to prevent nausea and vomiting induced by highly emetogenic chemotherapy. Annals of Oncology, 20, 1860–1866.

To evaluate the safety, efficacy, and pharmacokinetics of palonosetron, in combination with dexamethasone in patients receiving highly emetogenic chemotherapy (HEC)

Patients were randomized to 1 of 3 single doses of palonosetron, IV bolus (0.075, 0.25, or 0.75 mg), before administration of HEC. Subjects also received dexamethasone (12–16 mg IV on day 1, 8 mg on day 2, and 4–8 mg on day 3). All patients were hospitalized at least one day after palonosetron administration. Patients were followed up to five days. Patients used a diary to record episodes of vomiting, degree of nausea, and use of rescue medication.

• The study consisted of 231 participants.
• Mean age was 61.7 years (SD = 8.9) for the 0.075 mg group, 62.1 years (SD = 8.8) for the 0.25 mg group, and 62.0 years (SD = 9.8) for the 0.75 mg group.
• The majority of patients were male (73.2%).
• The majority of patients had lung cancer (95%), primarily non-small cell lung cancer (NSCLC).
• Patients were receiving cisplatin ≥ 50 mg/m².
• Patients were either chemotherapy naïve or had only received low or minimally emetogenic chemotherapy previously.

The study was conducted at multiple sites in Japan.

All patients were in active treatment.

This was a randomized, double blind, dose-ranging study.

• Patient diaries were used to record the date and time of emetic episodes, degree of nausea on a 0–3 scale, and use of rescue medication.
• Complete response (CR), defined as no emesis and no rescue medication, was recorded during the acute, delayed, and overall phases.
• Complete control (CC), defined as no emetic episodes, no rescue medication, and no more than mild nausea, was recorded during acute, delayed, and overall phases.
• Time to treatment failure, including time to first emetic episode or first administration of rescue medication, was recorded.
• Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) were recorded.
• Pharmacokinetic analysis (palonosetron and M9 in plasma for the maximum plasma concentration, area under the curve, terminal half-life, total clearance, volume of distribution) was conducted.

• CR rates during acute phase were 77.6%, 81.8%, and 79.5% in all groups, without significant differences in different dose groups.
• CR rates increased in a dose-dependent manner during the delayed and overall phases.
• CR rates in the delayed phase were 38.3%, 49.4%, and 56.4% respectively by dose group.
• Time to treatment failure was significantly longer in the 0.75 mg group than 0.075 mg group (p = 0.0376).
• The incidence, intensity, and relation of adverse effects to palonosetron were similar among the three dose levels.
• The most frequent adverse events were constipation and headache, and most adverse events were mild to moderate.

Palonosetron at doses of 0.25 mg and 0.75 mg was shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) in the acute phase in patients treated with HEC. CR rates in the delayed phase were less than 60% overall.

• The study did not include administration of aprepitant for HEC-related CINV.
• No discussion was provided regarding participant compliance with keeping the diary, which was the main measure for CR.
• The CR definition did not address nausea experience, and CC was not reported in detail, which addresses nausea control.

Increasing the dose of palonosetron on day one could contribute to better control of CINV during the delayed and overall phases of HEC.