Nadaraja, S., Mamoudou, A.D., Thomassen, H., Wehner, P.S., Rosthoej, S., & Schroeder, H. (2012). Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate. Pediatric Blood & Cancer, 59, 870–873.

To examine the effect of a single dose of palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) in children 18 years of age and younger with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate (HD MTX) (5 g/m²)

This study was a prospective analysis of the effectiveness of palonosetron given as a single dose (5 mcg/kg) prior to the administration of HD MTX in children 18 years or younger with ALL. Both MTX-naïve patients and previously treated patients were included.  Data was collected on 138 courses of chemotherapy with a total of 53 patients.  Response was determined by patient/parent questionnaires and patient records. Authors described the questionnaires as reporting the occurrence of emesis, the intensity of nausea, and the use of rescue therapy at six-hour intervals from day 1 until discharge. Intensity of nausea was measured using a visual analogue score (VAS) ranging from 0 to 10. Complete response was defined as no emetic episodes and no use of rescue medications during the acute phase (0–24 hours) and the delayed phase (24–66 hours).

• This study reported on 53 patients.
• Ages ranged from 2–18 years.
• The sample was 60% male and 40% female.
• All patients had been diagnosed with ALL and were receiving 5 g/m² HD MTX.

This was a multi-site study conducted in Denmark.

• Patients were in active antitumor treatment.
• This study has application for pediatrics.

This was a prospective trial.

• The questionnaire was not specifically identified, and no reliability data was provided.
• A 0–10 VAS was used to measure nausea intensity.

• Complete response (i.e., no emesis and no rescue therapy) was achieved in 84.1% of courses during the acute phase and 60.1% of courses during the delayed phase.
• During the acute phase, 92% of courses were completely free of emesis. During the delayed phase, 86.2% were free of emesis.
• During the acute phase 89.9% of patients did not receive any rescue therapy, compared to 65.2% during the delayed phase.
• Additionally, 76.8% of courses were free of nausea during the acute phase, and 78.3% of courses were free of nausea during the delayed phase.

This study demonstrated that a single dose of palonosetron was effective in the prevention of CINV in children 18 years old and younger with ALL receiving HD MTX both in the acute and delayed phases.

• The sample size was small with fewer than 100 patients.
• A risk of bias exists because no control group or random assignment was included. The sample characteristics also introduce a risk of bias.
• The measurements and methods were not well described and the validity and reliability of the tools was questionable.
• No data regarding the expected frequency of nausea or vomiting in this population or regimen was included.
• Some patients also received intrathecal (IT) MTX and anesthesia prior to receiving HD MTX, which could have impacted results.
• The investigators used multiple cycles from the same patients, which could introduce bias if patients had a history of CINV.

Palonosetron has been effective for moderate to highly emetogenic chemotherapy in acute and delayed CINV in adults. This study demonstrated that a single dose of palonosetron was effective in preventing both acute and delayed phase CINV in the majority of children under age 18 with ALL receiving HD MTX.  Prospective randomized controlled trials should be conducted in other pediatric oncology populations to determine generalizability of these findings.