Chemotherapy-induced nausea and vomiting are among the most distressing side effects of anti-cancer treatment, particularly for those receiving highly emetogenic regimens such as anthracycline plus cyclophosphamide combinations. This major side effect compromises a patient’s quality of life and willingness to continue therapy. Therefore, there is a crucial need to devise an effective antiemetic management approach for optimizing cancer care and patient well-being.
Against this backdrop, a new study, led by Professor Mitsue Saito and Dr. Hirotoshi Iihara from Japan, was made available online on June 17, 2025, and published in Volume 26, Issue 7 of the journal The Lancet Oncology on July 1, 2025, examined whether a 5 mg dose of olanzapine taken at home after chemotherapy could reduce nausea and vomiting in patients with breast cancer while minimizing the sedative effects associated with the standard 10 mg dose.
“While multiple studies have examined 10 mg of olanzapine and confirmed its effectiveness for nausea control, at this dose it often causes sedation, raising safety concerns,” explains lead author Prof. Saito. “Beyond the commonly observed sedation, olanzapine at the 10 mg dose can cause serious adverse effects, including sedative effects such as daytime sleepiness and loss of consciousness.”
“The study was inspired in part by three patients with breast cancer who attended an antiemetic guideline meeting at MASCC 2015 in Copenhagen. They spoke about the burdensome sedative side effects of olanzapine, a concern that helped shape the trial’s patient-centered design,” says Prof. Saito.
This phase 3, double-blind, placebo-controlled trial enrolled 500 female patients with breast cancer in Japan receiving outpatient anthracycline plus cyclophosphamide-based chemotherapy. Participants were randomly assigned to receive either olanzapine 5 mg or placebo in combination with standard triplet antiemetic therapy (palonosetron, dexamethasone, and an NK-1 receptor antagonist). The olanzapine 5 mg was taken at home after chemotherapy to help avoid sedation during hospital travel or treatment.
“This study uniquely investigates the timing of olanzapine 5 mg administration, given within 5 hours post-chemotherapy administration and before the evening meal, to reduce sedation during hospital visits and transportation. This approach takes into account the onset of nausea and vomiting reported in previous studies. Among highly emetogenic chemotherapies, there is a significant difference between cisplatin, which usually requires hospitalization for treatment, and other chemotherapies such as anthracycline-based regimens that are typically administered on an outpatient basis,” says Dr. Iihara. The primary endpoint of the study was to investigate the proportion of patients achieving complete response, defined as no vomiting and no rescue medication use during the overall phase (0–120 hours post-anthracycline plus cyclophosphamide initiation).
The results demonstrated significant improvement, with 58.1% of patients in the olanzapine 5 mg group achieving a complete response during the first 5 days after chemotherapy, compared to only 35.5% in the placebo group. Benefits also extended to delayed nausea and vomiting across a 7-day observation period.
While some patients reported drowsiness, the incidence of severe or very severe concentration impairment was low, occurring in 10% of patients in the olanzapine 5 mg group vs. 14% in the placebo group. Additionally, no major adverse events were observed in either group, indicating that there were no treatment-related deaths in either group.
The olanzapine 5 mg dose offers an important financial and clinical advantage over the commonly used 10 mg. By reducing side effects and cost, this strategy may make antiemetic treatment more accessible, particularly in lower-resource settings.
These new findings suggest that an olanzapine 5 mg regimen, especially when administered after chemotherapy, can be just as effective, with fewer side effects. Although the study focused on Japanese women with breast cancer, the results are expected to influence international practices and future guideline updates.
In addressing both physical and financial toxicity and putting patients’ voices at the center of the research, this trial represents more than a treatment tweak. It’s a step toward more humane, equitable cancer care.
Reference
Authors
Mitsue Saitoa, Hirotoshi Iiharab, Mototsugu Shimokawac, Ryoko Udagawad, Michiko Tsuneizumie, Manabu Futamuraf, Yuko Ishikawag, Hideaki Ogatah, Hiroko Bandoi, Hiroaki Shimaj, Keiko Hosoyak, Toru Mukoharal, Kenichiro Tanakam, Tomoki Ikutan, Takahiko Kawateo, Kazushige Ishidap, Katsuya Nakaia,q, Toshitaka Uomoria, Goro Kutomia,j, Rie Ozekia,r, and Naotake Yanagisawas
Title of original paper
Overall efficacy and safety of olanzapine 5 mg added to triplet antiemetics for an anthracycline-containing regimen in patients with breast cancer: a phase 3, double-blind, randomised, placebo-controlled trial
Journal
The Lancet Oncology
DOI
https://doi.org/10.1016/S1470-2045(25)00233-5
Affiliations
aDepartment of Breast Oncology, Juntendo University
bDepartment of Pharmacy, Gifu University Hospital
cDepartment of Biostatistics, Yamaguchi University Graduate School of Medicine
dDepartment of Pharmacy, National Cancer Centre Hospital, Chuo-ku
eDepartment of Breast Surgery, Shizuoka General Hospital
fDepartment of Breast Surgery, Gifu University Hospital
gDepartment of Breast Oncology, Juntendo Urayasu Hospital
hDepartment of Breast and Endocrine Surgery, Toho University
iDepartment of Breast and Endocrine Surgery, Institute of Medicine, University of Tsukuba
jDepartment of Surgery, Surgical Oncology and Science, Sapporo Medical University Hospital
kDivision of Breast and Endocrine Surgery, Tottori University Hospital
lDepartment of Medical Oncology, National Cancer Centre Hospital East
mDepartment of Surgery, Juntendo University Shizuoka Hospital
nDepartment of Pharmacy, National Hospital Organization Shikoku Cancer Centre
oDepartment of Breast Surgical Oncology, Tokyo Medical University;
pDepartment of Surgery, Iwate Medical University
qDepartment of Breast Surgery, Juntendo University Nerima Hospital
rFaculty of Pharmacy, Juntendo University
sClinical Research and Trial Centre, Juntendo University Hospital
About Professor Mitsue Saito
Dr. Mitsue Saito is a breast cancer specialist at the Department of Breast Oncology, Juntendo University in Tokyo, Japan. Known for her compassionate approach to patient care, her work focuses on improving the everyday experiences of people going through cancer treatment. Her research focuses on easing the side effects of chemotherapy, like nausea and vomiting, so that patients can feel more comfortable and supported. Inspired by the voices of real patients, Professor Saito designs studies that prioritize what matters most to them. Her work is helping to shape more humane, practical, and affordable cancer care in Japan and beyond.
About Dr. Hirotoshi Iihara
Dr. Hirotoshi Iihara is a clinical pharmacist at the Department of Pharmacy, Gifu University Hospital in Gifu, Japan. With a strong background in pharmacology and patient-centered research, he focuses on making cancer treatment safer, more tolerable, and more accessible. Dr. Iihara is passionate about reducing both the physical and financial burdens of supportive therapies, especially for patients undergoing chemotherapy. He believes that listening to patients’ needs is key to better care, and his work reflects a commitment to practical, real-world solutions that can improve outcomes and quality of life for people facing cancer around the world.
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