Olanzapine: A significant breakthrough in reducing chemotherapy induced nausea and vomiting.

The worst fear patients have when they are diagnosed with metastatic cancer is chemotherapy-induced nausea and vomiting, and Olanzapine (OLN) is ‘A Milestone in Antiemetics’, for treating and alleviating the symptoms of these patients. 

This article is mainly based on talk by Mark Kris from Memorial Sloan Kettering Cancer Center and work by Rudolph M. Navari, MD, PhD. He is currently based in Geneva, Switzerland, serving as Director of the World Health Organization Cancer Care Program in Eastern Europe.

The most emetogenic drugs used in cancer chemotherapy are anthracycline and doxorubicin combinations and cisplatin.

A randomized, double-blind, phase III trial was performed in patients who have not received chemotherapy earlier with 192 patients in the olanzapine arm and 188 in the placebo arm. The two groups were well matched for gender, age and diagnosis.

All the patients received cisplatin (≥ 70 mg/m²), or cyclophosphamide (600 mg/m²) plus an anthracycline (60 mg/m²)   and standard combination of   aprepitant, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist (ie, palonosetron, ondansetron, or granisetron), and dexamethasone pre and post therapy.

Only the study group received 10 mg of oral olanzapine on day 1 before the chemotherapy and day 2 and 4 post chemotherapy while the control group received a matching placebo.

The primary end point was no nausea and a secondary endpoint was complete response (no emesis, no rescue).

It was seen that the drug was able to improve nausea significantly in all the three phases namely   acute (0–24 hours post chemotherapy), delayed (24–120 hours post chemotherapy), and overall (120 hours post chemotherapy) phases. Patients on olanzapine also had a significantly better complete response than the placebo group.

The only side effect observed with the drug was mild sedation on second day, which resolved on further dosing on day 3 and 4.

Dr Mark Kris calls this trial as landmark one as there was no treatment for chemotherapy induced nausea in decades, even the addition of 5-HT3 antagonist along with newer antiemetics failed to improve the nausea.

Olanzapine is approved by the U.S. Food and Drug Administration (FDA) as an antipsychotic but does not have approval as an antiemetic.

The investigators noted that the study results were consistent with current guidelines from the National Comprehensive Cancer Network, which recommends the use of olanzapine with standard antiemetics as an option for preventing chemotherapy-induced nausea and vomiting in patients receiving emetogenic chemotherapy.

References

http://meetinglibrary.asco.org/content/155048-165

Navari R, Qin R, Ruddy J, et al: Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC): Alliance A221301, a randomized, double-blind, placebo-controlled trial. 2015 Palliative Care in Oncology Symposium. Abstract 176. Presented October 9, 2015.

National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Antiemesis, Version 2.2015. Available at nccn.org. Accessed April 15, 2016