Hocking, C.M., & Kichenadasse, G. (2014). Olanzapine for chemotherapy-induced nausea and vomiting: A systematic review. Supportive Care in Cancer, 22(4), 1143–1151. 

STUDY PURPOSE: To assess the efficacy of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) and treating breakthrough CINV with a secondary purpose of evaluating the side effects associated with olanzapine

 

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, Embase, and the Cochrane Database of Systematic Reviews

 

KEYWORDS: Nausea and chemotherapy, vomiting and chemotherapy, and olanzapine

 

INCLUSION CRITERIA: Trials of adult patients receiving moderately or highly emetogenic chemotherapy where olanzapine was used as an intervention; only randomized controlled trials were evaluated.

 

EXCLUSION CRITERIA: Exclusion criteria were not delineated.

TOTAL REFERENCES RETRIEVED: 217 studies were identified (23 from Medline, 203 from Embase, and four from Cochrane). 196 studies excluded because of non-randomized trials and non-focused on CINV. 21 texts underwent second screening and again, 15 studies were excluded for being non-randomized and non-focused on CINV.  

 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Jadad scale was used to evaluate the final six trials. A higher score (range 0–5) indicates greater methodological rigor in terms of randomization, blinding, and accountability. For trials looking at prevention, two scored 4 out of 5 with the other study at 3 out of 5. With breakthrough trials, one scored 5 on the Jadad scale with the other two, which where unpublished reports, scoring 2 out of 5.   

FINAL NUMBER STUDIES INCLUDED = 6 (3 prophylaxis of CINV, 3 breakthrough CINV) 

 

TOTAL PATIENTS INCLUDED IN REVIEW = 488 (prophylaxis of CINV), 323 (breakthrough CINV) 

 

KEY SAMPLE CHARACTERISTICS: Group characteristics were broken down to two groups. One is prophylaxis of CINV and the other is breakthrough CINV. Among the 488 patients in the prophylaxis group, age range was 18–81 years, and the group included 267 females and 221 males. Primary cancer sites were not identifiable in one trial of 18 patients. Of the other 470 patients, 38% had breast cancer, 29% had non-small cell lung cancer, and 9% had lymphoma. Highly emetogenic chemotherapy consisted of cisplatin at > 70 mg/m² in 56.5%, doxorubicin and cyclophosphamide in 42.9%, and dacarbazine in less than 1%. The breakthrough group included 323 patients. Age range was 37–85 years and included 154 females and 169 males. A breakdown of cancer diagnoses and regimens was not described in two trials totaling 215 patients. In the remaining trial of 108 patients, 50% were patients with breast cancer, 34% were patients with non-small cell lung cancer, 9% were patients with lymphoma, and 6% were patients with bladder cancer. Cisplatin at > 70 mg/m² was used in 41% of patients, while doxorubicin and cyclophosphamide were used in 59% of patients.   

In the prophylaxis group, complete response was the primary endpoint evaluated in the acute and delayed phases without any statistical significance. One trial reported more sleepiness with olanzapine than the controls, but another trial reported no differences between olanzapine and aprepitant. In one trial, there were significant differences between olanzapine and aprepitant with secondary endpoints of delayed nausea (69% versus 38%; p < 0.01) and no overall nausea (69% versus 38%; p < 0.01). In another large trial, olanzapine was added to a 5-HT3 antagonist and dexamethasone and compared to controls. There was statistical significance in delayed and overall complete response rates in highly (overall CR = 79% versus 57%; p < 0.05) and moderately (overall CR = 89% versus 76%; p < 0.05) emetogenic chemotherapy. One small study of aprepitant compared with olanzapine showed no statistical significance.  

 

In the breakthrough group, one trial compared olanzapine versus metoclopramide and found statistical significance in the olanzapine-treated patients with emesis (70% versus 31%; p < 0.01) and no nausea (68% versus 23%; p < 0.01). The second trial compared olanzapine with metoclopramide and dexamethasone at 66%, 36%, and 37% complete response rates, respectively. The other trial compared olanzapine and dexamethasone with metoclopramide and prochlorperazine at 66%, 36%, and 20% complete response rates, respectively.