For the prevention and treatment of CINV, clinical practices were mostly in compliance with the requirements of the national comprehensive cancer network (NCCN), the American Society of Clinical Oncology (ASCO). In order to further improve the effective control rate of nausea and vomiting in the delayed phase, authoritative international guidelines such as the Multi-National Association Supporting Care Cancer (MASCC) and the European Society for Medical Oncology (ESMO) have been issued. Based on data from various clinical studies, the guidelines have been continuously adjusted. The application of multiple drugs in combination for the prevention and treatment of CINV is recommended in the relevant clinical application guidelines. Based on the traditional three-drugs antiemetic regimen, olanzapine is introduced into the guidelines as a class of anti-psychotic drugs, and its efficacy has been recognized through clinical application both in China and abroad. However, looking back at the current clinical studies on CINV, both the traditional triple antiemetic regimen and the quadruple antiemetic regimen recommended by NCCN in 2020 (based on the addition of olanzapine to the traditional triple antiemetic drug) contain dexamethasone.
However, studies have shown that about 20% of non-diabetic cancer patients develop steroid-induced diabetes when using dexamethasone to prevent CINV. For diabetic tumor patients, the use of dexamethasone will aggravate blood glucose fluctuation and make blood glucose more difficult to control, thus aggravating the disease and even causing serious consequences. In addition to affecting the level of blood glucose, studies have also revealed that the glucocorticoid can inhibit T-cells activity by inhibiting interleukin-2-mediated T-cells proliferation and activation, and inducing T-cells apoptosis, thereby affecting the efficacy of immune checkpoint inhibitors. A retrospective analysis study examined the effect of dexamethasone on the efficacy of PD-1/PD-L1 inhibitors. This study included 640 patients with NSCLC, and the results showed that the baseline use of glucocorticoid for patients from two cancer centers significantly reduced the ORR, PFS, and OS of PD-1/PD-L1 inhibitors. Glucocorticoids may be an independent risk factor for poor prognosis in patients after treatment with immune checkpoint inhibitors.
The reduced use of dexamethasone and the recommended use of antipsychotic drugs have become a trend in the development of antiemetic guidelines in the new era. Most clinical studies on the prevention and treatment of CINV in China and abroad focus on the addition of olanzapine in the traditional three-drug antiemetic regimen, or the replacement of olanzapine only when dexamethasone cannot be tolerated. As for the nausea and vomiting caused by hyperemesis chemotherapy, there is currently no complete scheme of "desamethasone removal" in China and abroad. In our study, 50 chemotherapy-induced hyperemesis patients were randomly divided into the control group (dexamethasone group) and the test group (olanzapine group) according to random number table. The CR of nausea in the control group receiving dexamethasone combined with fosaprepitant and palonosetron in the overall observation, acute and delayed phases were 57%, 86% and 74% respectively. While the CR of vomiting during the overall observation, acute and delayed phases were 91%, 100% and 94% respectively in the control group. The patients in the test group who received the three-way antiemetic regimen of olanzapine combined with fosaprepitant and palonosetron orally achieved the complete remission rates of 66%, 84% and 81% of nausea in the overall observation period, acute period and delayed period respectively, and the complete remission rates of vomiting reached 89%, 95% and 92% respectively. Therefore, the antiemetic effect of the three-drug regimen containing olanzapine was not only not inferior to that of the traditional three-drug regimen in the control group. And is not lower than the olanzapine-containing quadruple antiemetic regimen recommended by the guidelines. Meanwhile, compared with similar studies at home and abroad, the olanzapine-containing quadruple antiemetic regimen also has good efficacy. In general, the efficacy of replacing traditional dexamethasone with 5-HT3 receptor antagonist and NK-1 receptor antagonist with olanzapine in controlling the nausea and vomiting in the acute phase caused by hyperemesis chemotherapy has reached the expectation.
With the transformation of modern medical model, the mental and psychological factors of patients with malignant tumor have been paid more and more attention. Patients with malignant tumor often suffer from different degrees of anxiety and depression. However, studies have shown that anxiety and depression are often related to chemotherapy-induced nausea and vomiting. Throughout the previous clinical studies on chemotherapy-related antiemesis containing olanzapine, mental, psychological, emotional, and sleep factors were not included in the clinical studies as observation indexes for clinical efficacy. Therefore, based on the development trend of clinical antiemesis guidelines in China and abroad, we made further exploration in this study and added observation indexes, so as to provide safe and alternative antiemesis regimens for patients with malignant tumors, especially for patients with glycosuria history, when receiving high-emesis chemotherapy regimens, which had certain guiding significance. Many studies have shown that olanzapine can significantly improve the symptoms such as pain, nausea, vomiting, insomnia, anxiety and depression in cancer patients and improve the quality of life of patients with advanced cancer. In this study, we assessed the anxiety and depression scores of patients before and after chemotherapy, and analyzed the correlation between the presence of anxiety and depression in patients and the occurrence of CINV. The results showed that the nausea and depression scores in the control group were significantly and positively correlated. Vomiting had no significant correlation with the anxiety and depression scores before and after chemotherapy, while nausea and vomiting were not significantly correlated with the anxiety and depression scores in the test group. Considering that the olanzapine application cycle in this study was only four days, and the observation cycle was short, it was not enough to have a positive effect on the anxiety and depression symptoms of the patient. In this study, 19 of 50 patients (38%) had sleep disorders, which deserves our attention. Analysis of the results of the General Sleep Disturbance Scale (GSDS) found that the sleep quality of patients in the test group at risk of sleep disorders was 100% improved after the observation period. We know that drowsiness and increased appetite are adverse reactions of olanzapine. Some patients suffer from daytime drowsiness, but in general, drowsiness and increased appetite are conditions that cancer patients are willing to accept.
On the whole, with the gradual change of medical model from "Biomedical Model" to "Bio-Psychological-Social Medical Model" in the new era, which also guides the change of guidelines and the new development direction of anti-vomiting in recent years. The decrement application of dexamethasone and the recommendation application of antipsychotic drugs have become the development trend of anti-vomiting guidelines at present. Most clinical studies on the prevention and treatment of CINV in China and abroad focus on the addition of olanzapine to the traditional antiemetic regimen, or the replacement of olanzapine only when dexamethasone cannot be tolerated. Whether olanzapine can completely replace dexamethasone in the antiemetic regimen will need more clinical research data to verify.