Rudolph M. Navari, MD, PhD
Olanzapine (Zyprexa) demonstrated an improvement in antinausea effects in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiation therapy for advanced stage head and neck and esophageal cancer when compared to fosaprepitant (EMEND), according to a study presented during the 2015 ASCO Annual Meeting.
The randomized, double-blind, phase III trial was performed in chemotherapy- and radiation-therapy naïve patients receiving concurrent local radiation and cisplatin- based chemotherapy. Fifty patients received 10 mg of olanzapine, along with .025 mg of palonosetron, and 20 mg of dexamethasone on day 1, followed by 10 mg of olanzapine on days 2 to 4, while 49 patients received 150 mg of fosaprepitant plus .025 mg of palonosetron and 12 mg of dexamethasone on day 1 followed by 4 mg of dexamethasone on days 2 to 3. The distribution of patients within the two groups was similar in gender, types of cancer, and radiotherapy regimens.
Patients were evaluated at the acute period (24 hours postchemotherapy), the delayed period (2-5 days postchemotherapy), and overall (0-120 hours postchemotherapy). The primary endpoint was complete response (CR). The secondary endpoint was a nausea score of zero on a scale of 0 to 10, with 10 equaling a high level of nausea and zero equaling no nausea.
CR was 88% in the olanzapine group and 84% in the fosaprepitant group (P
<.05) in the acute time frame, and 76% in the olanzapine group and 73% in the fosaprepitant group in both the delayed and complete time frames (P
For the secondary endpoint of nausea control, there was no significant difference between the olanzapine group and the fosaprepitant group in the acute phase, with 86% of patients in the olanzapine arm experiencing no nausea compared with 77% (P
<.05) in the fosaprepitant arm. However, there was a significant difference favoring olanzapine in the delayed and overall phases, with 71% of patients in the olanzapine arm experiencing no nausea compared with 41% (P
<.01) in the fosaprepitant arm in both phases. This benefit was limited to nausea and did not include vomiting.
“In combination with palonosetron and dexamethasone, olanzapine was comparable to fosaprepitant in the control of emesis in patients receiving concurrent highly emetogenic chemotherapy-radiation treatment,” said lead author on the study, Rudolph M. Navari, MD, PhD, professor of Medicine, associate dean and director, Indiana University School of Medicine.
The drugs were both well tolerated, and there were no grade 3 or 4 toxicities in either arm. CR and control of nausea in subsequent chemotherapy cycles were equal to or greater than cycle one for both regimens.
Olanzapine is currently approved by the FDA as an antipsychotic and is not approved for the control of nausea.
Previous studies have looked at olanzapine as an antiemetic. In a phase II trial looking at the prevention of chemotherapy-induced nausea and vomiting in patients receiving their first course of either HEC or moderately emetogenic chemotherapy (MEC), olanzapine was given with granisetron and dexamethasone prechemotherapy and with dexamethasone postchemotherapy.
In this study, nausea was found to be very well controlled in the patients receiving HEC, with no patient having nausea in the acute or delayed periods. Nausea was also well controlled in patients receiving MEC, with no nausea in 85% of patients in the acute period and in 65% of patients in the delayed and overall periods. There were no grade 3 or 4 toxicities.
The phase III study presented during the meeting confirms these findings, said Navari.
“Our results are consistent with current NCCN guidelines, recommending olanzapine regimen as an option for chemotherapy-induced nausea vomiting prophylaxis for patients receiving HEC,” he said.
Navari R, Nagy C. Olanzapine versus fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent chemoradiation treatment. J Clin Oncol. 2015;33 (suppl; abstr 9502).