1,2,3,5Hindu College of Pharmacy.
4Medical Oncologist, Guntur General Hospital.
Background: Chemotherapy-induced nausea and vomiting (CINV) remain among the most distressing side effects for patients receiving platinum-based and AC-T chemotherapy regimens. Despite progress in antiemetic therapy, many patients still suffer from suboptimal CINV control, compromising quality of life and adherence to treatment. Objective: To evaluate the effectiveness and safety of low-dose olanzapine as an adjunct to standard antiemetic therapy for the prevention of both acute and delayed phases of CINV. Methods: A prospective, randomized observational study was conducted at the Department of Oncology, Government General Hospital, Guntur, India, between November 2023 and April 2024. Eighty patients were randomly allocated into two groups: one receiving standard antiemetic therapy alone (n=40), and the other receiving an additional low-dose olanzapine (2.5 mg orally) prior to chemotherapy (n=40). The incidence and severity of acute (0–24 hours) and delayed (24–120 hours) CINV were recorded and analyzed. Results: Patients receiving low-dose olanzapine experienced significantly greater reductions in both acute and delayed CINV compared to the control group (p<0.05). Complete response rates were higher in the olanzapine group. Notably, the 2.5 mg dose also demonstrated an advantage in minimizing daytime sedation compared to previously reported outcomes using 5 mg and 10 mg doses, while maintaining similar antiemetic benefits. Adverse events were mild and did not differ significantly between groups. Conclusion: Low-dose olanzapine (2.5 mg) is an effective and well-tolerated option for preventing CINV when used alongside standard antiemetic regimens. Furthermore, this lower dose reduces the risk of daytime drowsiness commonly seen with higher doses, offering a favorable balance between efficacy and tolerability.
Chemotherapy remains a cornerstone in the treatment of cancer, yet it is frequently associated with challenging side effects such as nausea and vomiting. CINV can affect up to 80% of patients undergoing highly emetogenic chemotherapy, even with current antiemetic protocols involving 5-HT3 receptor antagonists, corticosteroids, and NK-1 receptor antagonists. Managing CINV effectively is crucial for maintaining patient comfort, enhancing quality of life, and ensuring adherence to chemotherapy regimens. Olanzapine, an atypical antipsychotic agent, has emerged as a promising antiemetic due to its broad antagonism of dopamine, serotonin, histamine, and muscarinic receptors. While previous studies have utilized 5 mg or 10 mg doses, concerns about excessive sedation have limited their use. Recent evidence suggests that a lower 2.5 mg dose may offer equivalent efficacy with improved tolerability, particularly regarding reduced daytime somnolence.
Figure 1 MOA of olanzapine in chemo induced nausea and vomiting
MATERIALS AND METHODS
Study Design and Setting: This was a prospective, randomized observational cohort study conducted at the Department of Oncology (Natcocenter), Government General Hospital, Guntur, India, from November 2023 to April 2024.
Participants: A total of 80 adult patients (≥25 years) scheduled to receive platinum-based or AC-T chemotherapy regimens were enrolled after obtaining informed consent. Exclusion criteria included known hypersensitivity to olanzapine, significant hepatic/renal/cardiac dysfunction, pregnancy, or use of interacting medications.
Randomization and Interventions: Patients were randomly assigned into two groups:
Outcomes Measured: Primary outcomes were the incidence and severity of acute (0–24 h) and delayed (24–120 h) CINV. Secondary outcomes included complete response (no vomiting and no rescue medication) and adverse effects.
Data Collection: Patient demographics, treatment details, and CINV symptoms were recorded using standardized forms and the MANE scale. Adverse events, particularly sedation, were carefully monitored.
Statistical Analysis: SPSS software was used for data analysis. Paired t-tests assessed within-group changes, while independent t-tests compared outcomes between groups. A p-value of <0.05 was considered statistically significant.
Statistical Summary:
Within-Group Changes (Paired t-test):
Between-Group Comparison (Independent t-test):
RESULTS
Baseline Characteristics:
|
Parameter |
Drug Group (n=40) |
No Drug Group (n=40) |
|
Age (Mean ± SD) |
52.4 ± 11.2 |
51.8 ± 10.7 |
|
Gender (M/F) |
12 / 28 |
10 / 30 |
|
Diagnosis |
Breast, GI, Lung |
Breast, GI, Lung |
|
Chemotherapy Regimen |
Platinum, AC-T |
Platinum, AC-T |
Nausea and Vomiting Scores:
|
Group |
Mean Nausea Before |
Mean Nausea After |
Mean Change |
Mean Vomiting Before |
Mean Vomiting After |
Mean Change |
|
Drug Group |
3.00 |
0.38 |
-2.62 |
2.85 |
0.42 |
-2.43 |
|
No Drug Group |
3.02 |
1.79 |
-1.24 |
2.91 |
1.63 |
-1.28 |
Daytime Sedation: Patients in the 2.5 mg olanzapine group reported minimal daytime sedation, in contrast to findings from earlier studies using 5 mg or 10 mg, which documented moderate-to-severe drowsiness bar graph showing comparison of nausea and vomiting score reduction between the two groups. line graph comparing reported somnolence for 2.5 mg, 5 mg, and 10 mg doses from literature.
Figure 2: Mean Change in Nausea and Vomiting Scores
Figure 3: Incidence of Daytime Somnolence by Dose Level
Safety Profile: Adverse effects were mild and comparable between groups, affirming the safety of low-dose olanzapine.
CONCLUSION
This study reinforces the effectiveness of low-dose olanzapine (2.5 mg) as a supportive antiemetic agent in managing chemotherapy-induced nausea and vomiting. It provides superior symptom control compared to standard therapy alone, without increasing the incidence of adverse effects. Importantly, this dose also reduces daytime somnolence observed with higher doses, suggesting it may be an optimal strategy for maintaining both efficacy and patient quality of life.
ACKNOWLEDGEMENTS
We express our sincere gratitude to Dr. D. Krishna Priyanka and Dr. T.V. Siva Rama Krishna for their mentorship and guidance. Special thanks to the staff of Hindu College of Pharmacy and the team at Government General Hospital, Guntur. We also thank the patients and their families for their cooperation and participation.
REFERENCES
Tanuja Bheemarasetti*, Karumanchi Nagur Meera, Tadimalla Sherli, Dr. T. V. Sivaramakrishna, Dr. D. Krishna Priyanka, Efficacy and Safety of Low-Dose(2.5mg) Olanzapine for Preventing Chemotherapy-Induced Nausea and Vomiting in Patients Undergoing Platinum-Based and AC-T Regimens: A Prospective Observational Study, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 4426-4430. https://doi.org/10.5281/zenodo.15745066
10.5281/zenodo.15745066
