Aprepitant Warrants More Study for CINV in Patients on FOLFOX for CRC

Aprepitant plus palonosetron and dexamethasone showed early promise for preventing chemotherapy-induced nausea and vomiting among patients with colorectal cancer who are undergoing FOLFOX chemotherapy, according to results of a small pilot study.

Aprepitant plus palonosetron and dexamethasone showed early promise for preventing chemotherapy-induced nausea and vomiting (CINV) among patients with colorectal cancer who are undergoing chemotherapy with fluorouracil, oxaliplatin, and leucovorin (FOLFOX), according to authors of a small pilot study reported in Supportive Care in Cancer.

“This study demonstrates that aprepitant added to standard antiemetic therapy of a 5-HT3 receptor antagonist and dexamethasone is an active regimen in patients treated with FOLFOX,” reported Alison Palumbo, PharmD, MPH, of the Oregon Health and Sciences University in Portland, Oregon, and coauthors.

Additional study is needed “to determine the role of aprepitant as primary prophylaxis against CINV with FOLFOX therapy,” the authors cautioned. “Aprepitant could certainly be considered as secondary prophylaxis in patients with significant CINV in their first cycle of FOLFOX.”

CINV is frequent among patients with colorectal cancer whose chemotherapy includes oxaliplatin. Standard prophylaxis with serotonin antagonists plus dexamethasone can control CINV among patients on moderately emetogenic chemotherapy regimens, including FOLFOX, but “significant numbers” of patients with colorectal cancer nevertheless suffer CINV, the authors noted. Grades 1 and 2 nausea and vomiting affects an estimated 41% of patients on FOLFOX, compared to only 23% of patients receiving only fluorouracil and leucovorin, and grade 3 and 4 nausea and vomiting have been reported for 5.8% of patients on FOLFOX and 1.4% on fluorouracil and leucovorin, the study authors noted.

Aprepitant is a selective neurokinin-1 antagonist. Previous research indicates that when used in combination with 5-HT3 receptor antagonists and dexamethasone for highly emetogenic cisplatin-based chemotherapy, aprepitant improves control of delayed CINV.

The study authors performed an uncontrolled multicenter, open-label phase II pilot study, administering a prophylactic antiemetic regimen including aprepitant to adults undergoing FOLFOX chemotherapy for colorectal cancer. The regimen consisted of 125 mg oral aprepitant on day 1 with palonosetron (0.25 mg, intravenously administered) and oral dexamethasone (12 mg), followed by 80 mg aprepitant on days 2 and 3 and oral dexamethasone (8 mg) on days 2, 3, and 4. Patients kept daily journals to record nausea, vomiting, rescue doses, appetite, and meals.

Fifty patients were evaluable after cycle 1 and 42 patients were evaluable by the end of cycle 4 of treatment. Overall complete response rates were high throughout cycle 1 and remained so, “suggesting a durability of response,” the authors reported.

“Patients still experienced delayed nausea, but the nausea was generally mild to moderate,” they reported.

Adverse events included diarrhea (13.6% of patients), fatigue (12.5%), and neutropenia (11%). Other reported adverse events included peripheral/sensory neuropathy (9%), infections (7%), anemia (6%), heartburn/GERD (5%), abdominal pain (5%), and rash (5%).

Aprepitant is relatively expensive ($845 for one 125 mg dose and two 80 mg doses) and its cost effectiveness with FOLFOX is unknown. Studies with highly emetogenic chemotherapy have found it to be cost effective in that setting.

Limitations for the pilot study included the absence of a control group and self-reported patient outcomes. Nor was patient compliance with antiemetic prophylaxis tracked. Despite these limitations, the authors described the findings as “promising” and argued that they warrant a phase III clinical trial.

The study was funded by Merck.