NEW YORK (Reuters Health) – Chemotherapy-induced delayed nausea remains a significant problem, despite the availability of second-generation antiemetics, researchers say.

In a study they conducted, over half of patients had delayed nausea and all of the antiemetic regimens they tested provided inadequate control.

What’s particularly “disappointing” is the fact that palonosetron (Aloxi), a second-generation 5-hydroxytryptamine receptor antagonist (5-HTRA), was no better than granisetron (Kytril), a first-generation 5-HTRA, at controlling delayed nausea, they write in the Journal of Clinical Oncology online August 20.

The researchers were similarly disappointed that aprepitant (Emend), a neurokinin-1 receptor antagonist, provided no significant benefit over prochlorperazine (Compazine).

On a brighter note, they say, dexamethasone on days 2 and 3 did enhance control of delayed nausea, a finding in line with prior research and current antiemetic guidelines.

In an email to Reuters Health, Dr. Joseph A. Roscoe, from the Department of Radiation Oncology, University of Rochester Medical Center in New York, said, “The newer more expensive drugs for preventing nausea and vomiting from chemotherapy are not always better than the older ones, especially for preventing nausea.”

In a double-blind randomized clinical trial, Dr. Roscoe and colleagues tested the following four regimens for controlling delayed nausea from chemotherapy containing a platinum-based drug or an anthracycline:

Group 1: palonosetron plus dexamethasone on day 1 with prochlorperazine on days 2 and 3.

Group 2: granisetron plus dexamethasone on day 1 with prochlorperazine on days 2 and 3.

Group 3: aprepitant plus palonosetron plus dexamethasone on day 1 with aprepitant plus dexamethasone on days 2 and 3.

Group 4: palonosetron plus dexamethasone on day 1 with prochlorperazine plus dexamethasone on days 2 and 3.

There were about 235 evaluable patients in each group.

The primary end point was average nausea assessed four times daily on days 2 and 3. The primary analyses were whether nausea control would be improved by using palonosetron vs granisetron on day 1 (group 1 vs group 2); by adding dexamethasone on days 2 and 3 (group 1 vs group 4); and by using aprepitant versus prochlorperazine (group 3 vs group 4).

The researchers say they found no evidence that palonosetron was more effective in controlling delayed nausea than the first-generation 5-HTRA (granisetron) when both were provided with dexamethasone on the day of treatment and prochlorperazine on days 2 and 3. There was no statistically significant difference between these two treatment conditions (group 1 vs group 2) in average or maximum nausea severity.

Likewise, aprepitant was not more effective than prochlorperazine when both were combined with palonosetron and dexamethasone (group 3 vs group 4). “We saw no statistically significant differences in average or maximum delayed nausea severity in this comparison,” they report.

“Also clear,” the authors wrote, “was our finding that the addition of dexamethasone to prochlorperazine on days 2 and 3 resulted in better control of delayed nausea than the same dose of prochlorperazine without dexamethasone.” Patients receiving dexamethasone had significantly lower average and maximum delayed nausea (group 1 vs group 4), leading the researchers to advise that any regimen “should include the addition of prolonged dexamethasone.”

Dr. Roscoe added in comments to Reuters Health, “nausea following chemotherapy is much more prevalent than vomiting and more research specifically on preventing and/or alleviating nausea is needed.”

The study was supported by the National Cancer Institute. Study medication was provided by MGI Pharma.

SOURCE:

Prevention of Delayed Nausea: A University of Rochester Cancer Center Community Clinical Oncology Program Study of Patients Receiving Chemotherapy

J Clin Oncol 2012.