Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer

Overview

Chemotherapy induced nausea and vomiting (CINV) is a common adverse effect in treatment of cancer, which influences the quality of life and adherence to treatment of patients and leads to dehydration, malnutrition and even death. Prevention and relieving the CINV is an important step to ensure the conduction of chemotherapy. Mechanism of CINV remains to be obscure, while most studies showed that it is mainly related to the following respects: ⑴ Chemotherapeutic agents stimulate gastrointestinal tract, which induces the release of neurotransmitters by chromaffin cells. Neurotransmitters bind to corresponding receptors, and then results in vomiting by stimulating the vomiting center; ⑵ Chemotherapeutic agents and the metabolites of them activate chemoreceptors directly, which causes vomiting. ⑶ Feeling and mental factors irritate cerebral cortex pathway directly. There are studies suggested that 5- hydroxytryptamine (5-HT) was related to acute nausea and vomiting induced by chemotherapy, which means 5-HT receptor antagonist would be a effective medicine for acute CINV. In addition, there are researches proclaimed that neurokinin-1 (NK-1) receptor antagonist, aprepitant, is a potent agent to relieve CINV. Thus, correlative guidelines recommend regimens with 5-HT receptor antagonist, NK-1 receptor antagonist and glucocorticoid as the standard treatment for strongly emetic chemotherapy regimens. But the prevention of moderately emetic chemotherapy regimens remains to be a problem in clinical practice. Besides, there is no study to demonstrate differences of mechanisms between acute CINV and delayed CINV. Olanzapine inhibits kinds of neurotransmitters which cause CINV, it is why this medicine is effective in both acute and delayed CINV. It can also alleviate anxiety, improve sleep quality and relieve pain in patients with cancer. The most common adverse effects of olanzapine are lethargy, body mass increase, fatigue, dry mouth, constipation, hyperlipidemia and hyperglycemia. Among them, the most common one is lethargy, which can oppose insomnia and excitation caused by dexamethasone. In a word, olanzapine is an agent with mild adverse effects, it is worth to be generalized. But there are still problems to be resolved in the application of olanzapine in CINV: ⑴ Aprepitant is expensive and not covered in medical care in China, which limits the application in patients. ⑵There is no large clinical trial to confirm the efficacy and safety of olanzapine in Chinese populations. To explore these issues better, investigators intend to compare the regimen with olanzapine, dexamethasone and 5-HT receptor antagonists with the regimen with placebo, dexamethasone and 5-HT receptor antagonists about the efficacy and adverse events in treatment of CINV. Investigators aim to provide an available therapeutic options for CINV, improve the quality of life and prolong the survival of patients with lung cancer.