Long-Acting Serotonin Antagonist Palonosteron To Prevent Nausea and Vomiting after High-Dose Melphalan and Autograft in Myeloma.

Palonosteron is a long-acting serotonin antagonist active in chemotherapy-induced nausea and vomiting (N/V). High-dose melphalan (HDM) is highly emetogenic. Even with pre-HDM anti-emetic administration, patients require anti-emetics in the following few days. This retrospective analysis was undertaken to see if the serotonin antagonist used prior to HDM affected anti-emetic use in the first week after HDM. The treatment group comprised 20 myeloma patients who received 140–200 mg/m2 melphalan the day prior to autograft (day -1), and 0.25 mg palonosteron IV prior to HDM. The control group comprised 49 myeloma patients receiving HDM in a similar fashion with 24 mg ondasteron IV prior to HDM. The groups were otherwise comparable. In accordance with our standard policy, no anti-emetic administration was scheduled from the day of transplant (day 0) onwards, and anti-emetics were administered based on patient needs as assessed by the nursing staff, the clinical team on rounds, and patient symptoms/request. The agents administered for breakthrough symptoms were lorazepam (1 mg/dose), prochlorperazine (10 mg/dose), metoclopramide (10 mg/dose), ondansetron (8 mg/dose), and promethazine (12.5 mg/dose) singly or in combination. As the table below shows, starting 2 days after palonosetron administration, about half the patient complained of some nausea and 10–25% experienced emesis. | Day | Nausea | Vomiting | |:--- | ------ | -------- | | | 10% | 5% | | 1 | 50% | 25% | | 2 | 60% | 5% | | 3 | 50% | 10% | | 4 | 60% | 15% | | 5 | 35% | 10% | | 6 | 40% | 25% | The palonosteron and ondansetron groups were compared based on the actual use of breakthrough anti-emetic medications starting the day after drug administration rather than symptoms to avoid bias. | Day | Any drug used for breakthrough | Ondansetron used for breakthrough | |:-------- | ------------------------------ | --------------------------------- | ------- | | (0=HSCT) | Palonosetron group | Ondansetron group | P | Palonosetron group | Ondansetron group | P | | | 30% | 84% | <0.0001 | 0% | 41% | <0.0001 | | 1 | 50% | 78% | 0.024 | 5% | 51% | <0.0001 | | 2 | 55% | 86% | 0.006 | 5% | 59% | <0.0001 | | 3 | 55% | 92% | <0.0001 | 5% | 59% | <0.0001 | | 4 | 70% | 90% | 0.042 | 20% | 47% | 0.056 | | 5 | 65% | 84% | 0.16 | 15% | 53% | 0.006 | | 6 | 75% | 86% | 0.29 | 20% | 47% | 0.056 | As the table above shows, the need for breakthrough anti-emetic medications was significantly less in the palonosetron group than in the ondansetron group. Approximately 50% of patients in the ondansetron group needed ondansetron every day after the initial dose on day -1. The proportion of patients getting ondansetron in the palonosetron group was 5–20% - significantly lower for first 4 days. For the 7 days studied, the average daily cost for breakthrough medications in the palonosteron group per patient was $11.37 (range 0.90–24.49) compared to $56.21 (range 28.15–62.97) in the ondansetron group. The total average drug cost per patient (including the prophylactic drug) was $473.89 in the palonosteron group and $511.30 in the ondansetron group. We conclude that the use of palonosetron before HDM and autotransplantation, because of the long-acting nature of the drug, results in significantly better control of N/V than ondansteron. In addition to being better from the symptomatic perspective, the decreased requirement for other agents to treat breakthrough N/V after palonosetron - especially reduction in the use of ondansetron - results in an overall cost saving.