A randomized open label trial comparing three antiemetic regimens (dexamethasone 8 mg/olanzapine 5 mg /olanzapine 10 mg) as maintenance therapy in patients who are on highly emetogenic chemotherapy.

Chemotherapy induced nausea and vomiting is quite a known problem in patients undergoing treatment for various oncologic diseases. It significantly affects the quality of life of patient and has both psychological and physical implications. In 1983, Coates et al. documented that patients undergoing chemotherapy reported nausea and vomiting as the first and second most severe side effects. Patients who

were on highly emetogenic agents in this era postponed, or even refused, potentially curative treatments. [1]

Since the 1990s, several new classes of novel classes of antiemetic’s have been developed, studied and commercialized and are being used as universal standard in chemotherapy regimens .Efficient mediation of these unpleasant and undesirable symptoms results in increased quality of life for the patient, better heath outcome ,more patient tolerance and reduction in number of hospital days stay. The incidences may be as high as 60–80% or more depending on the chemotherapeutic agent used. A study on the Japanese population receiving moderately emetogenic chemotherapy (MEC) has been reported to produce an

incidence of nausea in 48 % patients even with use of antiemetic prophylaxis [2].

Only few newer antiemetic’s has been approved in the last few years and very few are under clinical trial. NK1receptor antagonists (NK1RA) like aprepitant and fosaprepitant or the recent additions like netupitant , orrolapitant are some significant developments in the recent years. Dexamethasone has been long used as effective agent for management of chemotherapy induced vomiting. Vardy et al [3] studied adverse reactions related to

dexamethasone when used to prevent late onset emesis in moderately emetogenic chemotherapy (MEC), including anthracycline plus cyclophosphamide (AC), and reported such moderate-to severe adverse reactions to DEX as insomnia (45%), indigestion and epigastric discomfort (27%), and agitation (27%). It is currently unknown whether daily dexamethasone for five consecutive days of cisplatin provides more harm than benefit due to the potential adverse effects of longer duration dexamethasone.A recent study published showed Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK1-RA and Palonosetron in HEC [4].

Olanzapine is atypical antipsychotic approved by the Food and Drug Administration (FDA).It blocks multiple neurotransmitters: dopamine at D1, D2, D3, and D4receptors; serotonin at 5-HT type 2a, 5-HT type 2c (5-HT2c), 5-HT3, and 5-HT type 6 receptors;catecholamines at alpha1-adrenergic receptors;acetylcholine at muscarinic receptors; and histamine at H1 receptors in the central nervous system [5, 6]. Common side effects are mild short-term sedation, weight gain and an increased risk of diabetes mellitus when used more than 6 months. As olanzapine act at multiple receptors, particularly the D2, 5-HT2c, and 5-HT3 receptors, which may be involved in nausea and vomiting, suggest its role as agent with anti emetogenic property. A single-institution phase 3 trial showed that olanzapine, when combined with a single dose of dexamethasone and a single dose of palonosetron, an HT3-receptor blocker, was effective in controlling early and longer-term nausea and vomiting in patients receiving highly emetogenic chemotherapy [7]. Additional single-institution phase 3 studies have shown that olanzapine when combined with standard  antiemetic agents improves control of nausea and vomiting in patients receiving moderately or highly emetogenic chemotherapy [8, 9].

A study done by Takako yanai et al [10] proved that both doses of 10 mg and 5 mg olanzapine provided a significant improvement in delayed emesis and a low dose of 5 mg olanzapine was determined as the recommended dose for further phase 3 studies based on higher response rates and lower somnolence rates. Olanzapine was administrated at a dose of 10 mg in most of the previous studies that investigated its antiemetic effect [11-15]. Tan et al. reported that somnolence occurred in 73 % of patients that received olanzapine at dose of 10 mg [13]. While several studies have evaluated the antiemetic effect of olanzapine at a lower dose of 5 mg, there have been few reports published with detailed information relating to adverse events at this dose [9, 16]. When single day chemotherapy is used single-day CT two phases of chemotherapy induced nausea and vomiting have been identified: an acute phase, usually beginning immediately after CT administration and resolving within about 24 h and a delayed phase, defined as starting 24 or more hours after CT and lasting for up to

120 h or more depending on the CT regimen used [17].