Aprepitant Helps Prevent CINV in Men With Germ Cell Tumors

Lawrence H. Einhorn, MD

The addition of aprepitant to standard antiemetic prophylaxis significantly improved the complete response (CR) rate in patients with germ cell tumors undergoing 5-day cisplatin combination chemotherapy regimens, according to the results of a phase III study.

The data also showed that aprepitant, a potent and selective oral nonpeptide neurokinin-1 receptor antagonist (NK1-RA), is well tolerated and does not increase the frequency of adverse events.

Aprepitant and the corticosteroid dexamethasone are routinely given for the prevention of chemotherapyinduced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy with single-day, cisplatin combination chemotherapy, Lawrence H. Einhorn, MD, Distinguished Professor of Medicine at Indiana University School of Medicine in Indianapolis, and colleagues observed. However, there are limited data on the use of this regimen in patients with germ cell tumors, which are responsible for 1% of cancers in American males.

Investigators with the Hoosier Oncology Group randomized patients who were receiving two identical courses of 5-day cisplatin-based chemotherapy to 125 mg of aprepitant on day 3 and 80 mg per day on days 4 through 7 or to placebo for their initial course. Patients then crossed over to the opposite treatment for their second course. Additionally, all patients received dexamethasone and a commercially available 5HT3 receptor antagonist (5HT3-RA; see Table for dosages). The researchers excluded palonosetron as a 5HT3-RA option because of its comparatively longer half-life than other 5HT3-RAs.

Table. Drug Schedule

Treatment

Aprepitant (PO)

Placebo (PO)

Days 1-2

Dexamethasone

20 mg + 5HT3-RA

Dexamethasone

20 mg + 5HT3-RA

Day 3

Aprepitant 125 mg + 5HT3-RA

Placebo + 5HT3-RA

Days 4-5

Aprepitant 80 mg + 5HT3-RA

Placebo + 5HT3-RA

Days 6-7

Aprepitant 80 mg + dexamethasone 4 mg twice per day

Placebo + dexamethasone 8 mg twice per day

Day 8

Dexamethasone 4 mg twice per day

Dexamethasone 4 mg twice per day

JTCC_Reg1_5HT3-RA indicates 5-hydroxytryptamine-3 receptor antagonist; PO, orally.

The primary endpoint was CR of both acute (days 1-5) and delayed (days 6-8) CINV, defined as no emetic episodes with no use of rescue medication.

Results in 60 patients who completed at least 5 days of both cycles showed a 42% overall CR rate with aprepitant, compared with 13% with placebo (P < .001).

Eleven patients (16.2%) had at least one emetic episode during the aprepitant cycle versus 32 patients (47.1%) with placebo.

Thirty-eight patients (78%) reported that they preferred the aprepitant cycle while 11 patients (22%) cited a preference for placebo (P <.001).

The aprepitant and placebo arms had similar toxicity rates, but aprepitant-treated patients were less likely to need rescue antinausea medications.

Einhorn and associates noted that they used dexamethasone only on days 1 and 2 of the acute phase in order to reduce the adverse effects of corticosteroids. They suggested that the failure to use dexamethasone on all 5 days of the acute phase may be a study drawback, but emphasized that the optimal length of dexamethasone treatment has not been determined.

Future research, they wrote, should test the use of fosaprepitant in patients with germ cell tumors. Fosaprepitant is a water-soluble analog of aprepitant that is rapidly converted to aprepitant after intravenous injection.

Albany C, Brames MJ, Fausel C, et al. Randomized, doubleblind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a Hoosier Oncology Group study [published online ahead of print August 20, 2012]. J Clin Oncol. doi:10.1200/JCO.2011.39.5558.