Giralt, S.A., Mangan, K.F., Maziarz, R.T., Bubalo, J.S., Beveridge, R., Hurd, D.D., … Schuster, M.W. (2011). Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation. Annals of Oncology, 22, 939–946.

• To explore the efficacy and safety of three different administration schedules of palonosetron for preventing emesis and nausea
• To assess the safety of the different palonosetron schedules and their impact on activities of daily living as a result of nausea and vomiting

• Patients were randomly assigned to 1 of 3 palonosetron administration schedules.
  • 0.25 mg IV 30 minutes prior to melphalan and transplant on day -2
  • Same dosage prior to treatment on days -2 and -1
  • Same dosage and timing on days -2, -1, and 0.
• Infusions of saline were given in groups 1 and 2 to simulate additional study drug doses as a control.
• All patients were given 20 mg IV dexamethasone on days -2 and -1 immediately before or after the study drug.
• Patients maintained daily diaries to record episodes and severity of nausea and vomiting, use of rescue medications, and adverse events.
• Patients completed nausea questionnaires on day -2 and day 0.
• Patients were followed for 7 days from day -2 to day +5.

• This study consisted of 73 participants.
• Ages of patients ranged from 32–78 years.
• The majority of patients were male (64%).
• All had multiple myeloma and were receiving melphalan and transplant.
• Less than one-third were chemotherapy naïve prior to the study.
• The majority of the patients were Caucasian (75%).

The study was conducted in an outpatient setting at Memorial Sloan Kettering Cancer Center in New York.

All patients were in active treatment.

This was a double-blind, randomized pilot study.

• The Osoba Nausea and Emesis Module questionnaire was used.
• Patients recorded nausea severity daily on a 4-point Likert-type scale (0 = none to 3 = severe) in diaries.
• Common Terminology Criteria for Adverse Events (CTAE v3.0) was used.

• No significant differences were found between groups for complete no-emesis rates, with about 40% of patients achieving complete prevention of nausea and vomiting.
• A trend toward increased complete response with additional doses of palonosetron was observed on day 0 (p = 0.015).
• Multiple days of palonosetron was associated with better daily relief as reflected in diaries, but this was not statistically significant.
• No significant differences were found between groups in amount of rescue medication used overall.
• During the 5 days post-transplant, a greater proportion of patients receiving multiple palonosetron doses reported no or minimal impact on activities of daily living from nausea or vomiting.
• Similar adverse events were seen across all study groups. Most frequent events likely related to the study drug were diarrhea, constipation, headache, insomnia, and flatulence.
• Most patients (80%) experienced emesis or required rescue medication even with multiple doses of palonosetron.

A multiple-dose schedule of palonosetron as used here was not associated with any increase in adverse events. No definitive conclusions can be drawn regarding the benefit of multiple-day administration of palonosetron.

• The sample size was small with fewer than 100 patients.
• Some measures of benefit appeared to be improved in the groups with multiday dosing of palonosetron; however, patterns were inconsistent.

Further evaluation of multiple-day schedules of palonosetron are warranted. Even with multiple dosing, 80% of these patients had episodes of emesis or required rescue medication, pointing to the continuing challenge to determine more effective methods and combinations to meet this patient need.