Hesketh, P.J., Wright, O., Rosati, G., Russo, M., Levin, J., Lane, S., … Makhson, A. (2012). Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer, 20, 1471–1478.

To determine if a single 90-mg dose of casopitant added to ondansetron and dexamethasone would improve control of chemotherapy-induced nausea and vomiting (CINV) over 0–120 hours following initiation of oxaliplatin-based, moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone and, as an optional component of the study, to measure the plasma concentration of 90 mg IV casopitant in patients enrolled in trials at various centers

Patients received 90 mg IV casopitant or IV placebo 30 minutes prior to oxaliplatin on day 1. All subjects received 8 mg IV dexamethasone and 8 mg ondansetron hydrochloride prior to starting the oxaiplatin on day 1, followed by five separate 8-mg doses at approximately 12-hour intervals on study days 1 to 3. Patients recorded efficacy data for the subsequent 120 hours.

To assess PK profiles, blood samples were obtained during cycle 1 of chemotherapy at the following times: predose, end of infusion, and 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after infusion. A final sample was taken between 30 and 48 hours after infusion.

• The study reported on 707 patients.
• Mean age was 61 years old.
• The placebo arm was 59% male and 41% female.
• The casopitant arm was 51% male and 49% female.
• Patients had been diagnosed with colorectal cancer and were receiving oxaliplatin doses between 85 and 130 mg/m² in their first cycle of therapy.

This was a multi-site study conducted at multiple settings at 89 centers (hospitals or outpatient clinics) in 11 countries.

• All patients were in active antitumor treatment.
• This study has application to elder care.

This was a phase III, multicenter, randomized, double-blind, active-controlled, two-arm, parallel-group study.

• Patients recorded the number of emetic episodes, the number of nausea episodes, and use of rescue medication in study diaries during the 120-hour assessment phase.
• Patients completed the Functional Living Index–Emesis (FLIE) and used a visual analog scale (VAS) to rate nausea.
• Blood samples were used to assess PK profiles.

No difference in the rate of CR was noted in the casopitant group compared to the placebo group for the overall (placebo 85%, casopitant 86%, p = 0.7273), acute (placebo 96%, casopitant 97%), or delayed phases (placebo 85%, casopitant 86%). At 24 hours after 90 mg IV casopitant administration, the plasma casopitant concentration was 24% lower than the values noted in prior studies with 150 mg oral administration. Casopitant was well tolerated by patients.

The addition of single, 90-mg, IV dose of casopitant did not improve control of CINV at any time during 120 hours following initiation of oxaliplatin-based MEC. Excellent control of CINV was achieved in this study population with the combination of ondansetron and dexamethasone alone.

• Important differences existed in the baseline sample and groups.
• Key sample group differences could influence results.
• Findings are not generalizable.
• A difference in nausea was reported between the groups at baseline.

The results of this study indicate that ondansetron and dexamethasone are sufficient enough to control CINV associated with oxaliplatin chemotherapy in the treatment of patients with colorectal cancer. This finding is contrary to other studies, and the explanation is somewhat unclear. The PK concentration of the 90 mg IV casopitant was lower than that seen in the oral casopitant. A direct comparison of the IV regimen and the oral regimen in combination with ondansetron and dexamethasone in this patient population is warranted, as this is a large oncology patient population.