Noor, R., Bedikian, A. Y., Mahoney, S., Bassett, R., Jr., Kim, K., Papadopoulos, N., … Homsi, J. (2012). Comparison of two dosing schedules of palonosetron for the prevention of nausea and vomiting due to interleukin-2-based biochemotherapy. Supportive Care in Cancer, 20, 2583–2588.

To compare efficacy of two dosing schedules of palonosetron for prevention of nausea and vomiting caused by interleukin-2- (IL2) based biochemotherapy

Patients who were treatment naïve were randomized to one of two dosing schedules for 0.25 mg IV palonosetron for prophylaxis of chemotherapy-induced nausea and vomiting (CINV). Schedule one was on days 1 and 4, and schedule two was on days 1, 3, and 5. All patients received the same chemotherapy/biotherapy regimen, which consisted of dacarbazine on day 1; cisplatin, vinblastine, and IL-2 on days 1-4; and interferon (IFN) alpha 2b on days 1–5 as part of a 21-day cycle. Patients also received 0.5–1 mg IV lorazepam every 8 hours. Rescue medications were 50 mg IV metoclopramide with 25 mg IV diphenhydramine every 4 hours, 10 mg IV prochlorperazine every 4 hours, or a combination of lorazepam, diphenhydramine, and haloperidol compounded in hospital pharmacy. An episode of nausea or vomiting was defined as nausea or vomiting of any severity reported by the patient or documented by the nursing staff at any time during the 21-day treatment cycle as well as the need for rescue medication during the first 7 days. Patient diaries were used to document episodes of nausea and vomiting and the antiemetic used to control them. Function Living Index-Emesis (FLIE) was used to assess the patient’s quality of life daily for days 1–7.

• The study reported on 30 patients with a median age of 53.
• The sample was 60% male and 40% female.
• Patients had been diagnosed with stage III–IV metastatic melanoma and had European Cooperative Oncology Group (ECOG) performance statuses of 0–1 and expected survival greater than eight weeks.

This was a single site, inpatient study conducted at the M.D. Anderson Cancer Center in Houston, TX.

Patients were undergoing the active treatment phase of care.

This was a randomized, two-group, comparison study.

• Patients used the FLIE to evaluate quality of life.
• Patient diaries were used to document episodes of nausea and vomiting and use of antiemetics.

Each group (schedule 1 and schedule 2) had 15 patients. For the first 7 days of treatment, more episodes of nausea were reported for schedule 1 than schedule 2, but the difference was not statistically significant (p = 0.16). A similar trend was observed when comparing the number of episodes of emesis during the first 7 days (p = 0.20), the number of antiemetic rescue doses required (p = 0.30), and number of episodes of nausea and emesis during the first 21 days. Evaluation of the FLIE revealed similar proportion of patients on schedule 1 and 2 experiencing interference with appetite, sleep, physical activity, social life, and enjoyment of life (p = 0.071).

Because of the small sample size, differences in dosing schedule efficacy cannot be determined with confidence. However, a trend toward better control of CINV was noted with more frequent palonosetron dosing.

• The sample size was small, with fewer than 100 patients.
• The study was not powered or designed to show statistical differences. The patients in the schedule 1 group had higher prevalence of liver metastasis; while not statistically significant, sample size may not be large enough to determine if this was significant.  

Corticosteroids for the prevention of biochemotherapy-induced nausea and vomiting are contraindicated because they cause lysis of lymphokine-activated killer (LAK) cells produced in response to IL-2, which makes control of CINV challenging. This study does not provide evidence to support use of antiemetic schedule 1 versus schedule 2. More research is needed.