Abstract
Purpose
Although previous standard antiemetic trials evaluated chemotherapy-induced nausea and vomiting (CINV) up to 120 h, recent evidence suggests that symptoms can persist well beyond this timeframe. However, the preventive efficacy of a triplet regimen including fosnetupitant (FosNTP) during the long-delayed phase (120–336 h) remains unclear in patients undergoing moderately emetogenic chemotherapy. This study aimed to prospectively evaluate the efficacy of FosNTP in preventing CINV during this extended long-delayed window.
Methods
This single-center, single-arm, prospective observational study recruited patients scheduled to receive oxaliplatin-based chemotherapy. The primary endpoint was the long-delayed (120–336 h) complete control (CC) rate. Key secondary endpoints included the long-delayed complete response (CR) rate and the overall (0–336 h) CC, CR, and total control (TC) rates. Relative risks for emetogenic events were assessed using a logistic regression model.
Results
The analysis included 100 patients. Most eligible patients received CapeOX (oxaliplatin + capecitabine) (92.0%). The long-delayed CC rate was 76.3%. The long-delayed CR and TC rates were 84.7% and 75.4%, respectively. Risk factors for CINV in participants who did not achieve CC during the long-delayed phase included age (odds ratio 0.954 [95% confidence interval 0.909–0.998]), female sex (8.808 [2.446–41.992]), and history of motion sickness (5.050 [1.118–27.548]).
Conclusion
The triplet regimen involving FosNTP showed promising results and potential utility for managing long-delayed CINV in patients receiving oxaliplatin-based chemotherapy. However, given the single-arm study design, further comparative trials are warranted to confirm these findings. Participants with high emetic risk factors—such as younger age, female sex, or a history of motion sickness—continued to experience suboptimal control.
Trial registration number and date of registration
jRCT1030230130.
Keywords: Fosnetupitant, Long-delayed CINV, Chemotherapy, Oxaliplatin, Antiemetics
Introduction
Chemotherapy-induced nausea and vomiting (CINV) significantly impairs patients’ quality of life [1–3]. CINV is one of the most distressing adverse events associated with cancer treatment [4–7] and may reduce the adherence to anticancer therapy [8, 9]. Consequently, effective control is essential for maintaining treatment continuity and achieving optimal clinical outcomes.
Current guidelines recommend a doublet antiemetic regimen involving a 5-HT3 receptor antagonist (5-HT3RA) and dexamethasone (DEX) for patients receiving moderate emetogenic chemotherapy (MEC) [10–12]. However, this regimen is often insufficient for oxaliplatin-based chemotherapy, and adding an NK1 receptor antagonist (NK1RA) or olanzapine is considered appropriate. Advances in antiemetic therapy have improved control of acute symptoms (0–24 h). The combination of an NK1RA with palonosetron (PALO) is preferred for MEC, as both 5-HT3RAs and PALO have demonstrated superior efficacy, particularly in preventing delayed-phase symptoms (24–120 h) [13–15].
Nonetheless, delayed CINV remains underrecognized, specifically in outpatient settings using highly or moderately emetogenic regimens without cisplatin [16]. Consequently, delayed-phase control rates may be overestimated. Despite NK1RA administration, 10–20% of patients continue to experience delayed symptoms [13–15, 17–19], indicating persistent gaps in prevention. Symptoms extending beyond 120 h (the long-delayed phase) may reduce adherence or lead to chemotherapy discontinuation, potentially worsening clinical outcomes [20].
Fosnetupitant (FosNTP) is a novel NK1RA that demonstrated non-inferiority to fosaprepitant when combined with PALO and DEX for highly emetogenic chemotherapy (HEC), with a more favorable safety profile [21, 22]. It has since been incorporated into the standard antiemetic regimens for HEC. Importantly, compared to first-generation NK1RAs such as aprepitant or fosaprepitant, which have short elimination half-lives of approximately 9 to 13 h, the active moiety of FosNTP exhibits an exceptionally long elimination half-life of approximately 144 h [21] and sustained NK1 receptor occupancy (remaining above 50% even at 168 h) [22]. Because of these unique pharmacokinetic and pharmacodynamic profiles, a single dose of FosNTP may exert a prolonged antiemetic effect that extends well into the second week of the chemotherapy cycle. This pharmacological durability is particularly relevant for regimens like CapeOX, where patients face ongoing, cumulative emetogenic risks due to 14 consecutive days of oral capecitabine. Therefore, this study aimed to prospectively evaluate the preventive efficacy of FosNTP during the extended long-delayed phase (120–336 h).
Although a recent network meta-analysis reported no statistically significant benefit of adding an NK1RA to MEC [23], the role of NK1RA in combination with PALO and DEX remains debated. The SENRI trial [13] involving patients receiving oxaliplatin-based chemotherapy demonstrated that adding an NK1RA improved delayed-phase complete response (CR; no vomiting and no rescue medication) and complete protection (no vomiting, no rescue medication, and no moderate or severe nausea) by more than 10% over 120 h. These findings indicate that NK1RA may also enhance control in the long-delayed phase of MEC. Crucially, in regimens such as CapeOX, which was administered to the majority of patients in this study, capecitabine is taken orally for 14 consecutive days (Days 1–14), exposing patients to potential emetogenic triggers across a full 2-week period (up to 336 h). Given the exceptionally long elimination half-life of FosNTP (approximately 144 h), assessing its efficacy over this entire 336-hour period is highly relevant to understanding its full clinical utility. Therefore, this study aimed to prospectively evaluate the efficacy of triplet antiemetic therapy including FosNTP and identify risk factors associated with uncontrolled CINV during the long-delayed phase in patients receiving oxaliplatin-based chemotherapy. Our findings may help refine antiemetic strategies and improve long-term control of CINV in patients receiving oxaliplatin-based chemotherapy.
Materials and methods
Study design
This single-center, prospective observational study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the ethical review board of the Institute of Medical Science, University of Tokyo (approval number: 2023-4-0420). The study was registered in the Japan Registry of Clinical Trials as jRCT1030230130. All patients provided written informed consent.
Participants
The study was initially designed to evaluate platinum-based regimens containing oxaliplatin or carboplatin for gastrointestinal and urological cancers. Owing to lower-than-expected enrollment, the protocol was revised to limit eligibility to patients receiving oxaliplatin-based chemotherapy for gastrointestinal cancer. The present analysis was conducted in accordance with the revised protocol. Inclusion criteria were: (i) a confirmed diagnosis of gastrointestinal or urological malignancy; (ii) planned oxaliplatin-containing chemotherapy with triplet antiemetic therapy (FosNTP, PALO, and DEX); (iii) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (iv) age > 18 years; and (v) written informed consent. Exclusion criteria were: (i) ongoing opioid therapy; (ii) current antiemetic use, including 5-HT3 receptor antagonists, NK1 receptor antagonists, corticosteroids, dopamine receptor antagonists, minor tranquilizers, antihistamines, or benzodiazepines; (iii) brain metastases with uncontrolled symptoms; (iv) concurrent abdominal or pelvic radiotherapy; (v) prior platinum-based chemotherapy within three months; (vi) nausea or vomiting within one week of study entry; or (vii) pregnancy or breastfeeding.
Chemotherapy
Eligible MEC regimens containing oxaliplatin included CapeOX (oxaliplatin 130 mg/m2, day 1, and capecitabine 1000 mg/m2 twice daily, days 1–14) and SOX (oxaliplatin 130 mg/m2, day 1, and tegafur/gimeracil/oteracil 80 mg/m2, days 1–14). Molecularly targeted agents or immune checkpoint inhibitors were permitted.
Antiemetic treatment
FosNTP (235 mg/body), PALO (0.75 mg/body), and DEX (6.6 mg/body) were administered intravenously approximately 30 min before chemotherapy initiation on day 1. To minimize corticosteroid-induced toxicities (e.g., insomnia, hiccups) and to accurately evaluate the independent, prolonged effect of FosNTP, a strict dexamethasone-sparing strategy was utilized. Specifically, the DEX dose on Day 1 was reduced to 6.6 mg, and no subsequent administration of DEX was performed on Day 2 and thereafter, in accordance with Japanese clinical consensus. Rescue antiemetics—metoclopramide, domperidone, alprazolam, or prochlorperazine maleate—were available to all participants. Patients received detailed instructions on their appropriate use. Olanzapine was not used for CINV prophylaxis.
Evaluation
Participants recorded CINV in daily diaries (Table 1) from 0 to 336 h after starting the first course of chemotherapy. Symptoms were documented in medical records, and laboratory data were reviewed at each visit. Clinical pharmacists and attending physicians assessed adverse event severity. Regarding rescue therapy, appropriate rescue medications were routinely prescribed in advance to all patients on Day 1 of chemotherapy. Patients were instructed to document the exact date and time of any rescue medication use in their daily diaries (self-report forms). In the efficacy analysis, the administration of any rescue medication at any point within a specific phase automatically classified that patient as a treatment failure (i.e., not achieving Complete Control, Complete Response, or Total Control) for that entire phase.
Table 1.
Self-reporting of adverse events
| Side effect self-report | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Name | Date | ||||||||
| Grade | |||||||||
| Nausea | None | ||||||||
| Mild | |||||||||
| Moderate | |||||||||
| Severe | |||||||||
| Rescue medication use (times) | |||||||||
| Tolerable (mild nausea; no anti-nausea drugs needed) | 1 | ||||||||
| If I use anti-nausea drugs, I can manage to eat | 2 | ||||||||
| I can hardly eat because of nausea | 3 | ||||||||
| Vomiting | Number of vomiting episodes | ||||||||
| Anorexia | I have a slight loss of appetite | 1 | |||||||
| I can eat with some difficulty | 2 | ||||||||
| I can hardly eat | 3 | ||||||||
| Malaise | Mild fatigue; however, it does not interfere with my daily life | 1 | |||||||
| I frequently need to lie down | 2 | ||||||||
| I lie down more than I am awake | 3 | ||||||||
| Bedridden all day long | 4 | ||||||||
| Diarrhea | Increased defecation frequency < 4 times a day compared to usual | 1 | |||||||
| Increased defecation frequency 4–6 times a day compared to usual | 2 | ||||||||
| Increased defecation frequency > 7 times a day compared to usual | 3 | ||||||||
| If you have any other symptoms of concern, please write them down. | |||||||||
Endpoints
The primary endpoint was long-delayed (120–336 h) complete control (CC), defined as neither vomiting nor moderate-to-severe nausea and no rescue medication use during the first chemotherapy cycle. Secondary endpoints were: (i) long-delayed CR and total control (TC) rates; (ii) CC, CR, and TC, defined as absence of vomiting and nausea without rescue medication throughout the entire observation period in the extended overall phase (0–336 h); (iii) risk factors associated with failure to achieve CC, CR, or TC; and (iv) time-to-treatment failure in each phase. An event was defined as vomiting or rescue medication use. The CC rate was defined as the proportion of patients experiencing no emetic episodes and moderate or severe nausea without rescue medication. The CR rate was defined as the proportion of patients experiencing no emesis without rescue medication, and the TC rate was defined as the proportion of patients experiencing no vomiting or nausea without rescue medication. These parameters were evaluated during the first chemotherapy cycle. Acute nausea was defined as occurring within 24 h of chemotherapy initiation, and delayed nausea as occurring between 24 and 120 h.
Sample size calculation
Owing to the descriptive nature of the primary endpoint analysis, no formal statistical power or sample size calculations were performed. The planned enrollment target was 100 participants, based on the estimated number of patients expected to undergo gastrointestinal cancer chemotherapy at our institution during the study period. To account for potential loss to follow-up, the recruitment target was increased by an additional 50 patients to ensure that at least 50 evaluable participants could be analyzed. The target sample size was set with reference to the descriptive approach used in the CONSOLE-BC study to evaluate safety and feasibility rather than comparative efficacy [24]. To minimize the impact of incomplete data and participant dropout, a safety margin of approximately 50 cases was incorporated into the sample size target.
Data collection
The following variables were recorded for analysis: sex, age, clinical stage, chemotherapy regimen, habitual alcohol consumption (defined as alcohol intake exceeding social drinking levels), history of hyperemesis gravidarum, history of motion sickness, and the timing of CINV onset. Patient self-reports of adverse events were used to determine the presence and severity of nausea and vomiting. CINV was assessed based on patient-reported outcomes. Data were collected between May 2023 and March 2025.
Data analysis
All evaluation parameters were summarized using descriptive statistical methods. To identify potential risk factors associated with uncontrolled CINV during the delayed phase (120–336 h), multivariable logistic analyses were conducted using sex, age, habitual alcohol consumption, history of hyperemesis gravidarum, and history of motion sickness as explanatory variables. Additionally, a time-to-antiemetic treatment failure analysis was performed using the Kaplan–Meier method to calculate cumulative incidence.
Results
Patients
We enrolled 106 patients between May 1, 2023, and March 2025 (Fig. 1). All eligible patients received FosNTP (235 mg/body), PALO (0.75 mg/body), and DEX (6.6 mg/body) intravenously 30 min before chemotherapy on day 1 and were observed for 336 h after administration. Six patients were excluded because of treatment regimen changes after inclusion (n = 4) or refusal of chemotherapy after inclusion (n = 2). A total of 100 patients were included in the final analysis. CapeOX was the most frequently administered regimen (92.0%). In total, 88.0% of patients had stage III cancer. All patients had an ECOG status of 0 (Table 2). No deaths occurred during the observation period.
Fig. 1.
CONSORT flow diagram. Of 106 enrolled patients, 106 met the inclusion criteria. Six patients were excluded: four changed their treatment regimen and two refused chemotherapy (detected after obtaining informed consent)
Table 2.
Demographics of enrolled patients
| Median age (range), years | 58 (31–82) | |
|---|---|---|
| Sex, n (%) | Male | 40 (40.0) |
| Female | 60 (60.0) | |
| Primary tumor site, n (%) | Colorectal | 92 (92.0) |
| Gastric | 8 (8.0) | |
| ECOG performance status, n (%) | 0 | 100 (100.0) |
| 1 | 0 (0.0) | |
| 2 | 0 (0.0) | |
| Clinical stage, n (%) | II | 6 (6.0) |
| III | 88 (88.0) | |
| IV | 6 (6.0) | |
| Alcohol consumption history, n (%) | Yes | 39 (39.0) |
| No | 61 (61.0) | |
| Experience with morning sickness, n (%) | Yes | 15 (15.0) |
| No | 85 (85.0) | |
| Motion sickness, n (%) | Yes | 14 (14.0) |
| No | 86 (86.0) | |
| Treatment regimen, n (%) | CapeOX | 92 (92.0) |
| SOX | 8 (8.0) | |
ECOG, Eastern Cooperative Oncology Group; CapeOX (oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice daily on days 1–14); SOX (oxaliplatin 130 mg/m2 on day 1 and tegafur/gimeracil/oteracil 80 mg/m2 on days 1–14)
No patients received combination therapy with molecularly targeted drugs or immune checkpoint inhibitors
Primary endpoint
The long-delayed CC rate in the first chemotherapy cycle was 76.3% (Fig. 2a).
Fig. 2.
(a) CC rate by phase; (b) CR rate by phase; (c) TC rate by phase. The CC rate was defined as the proportion of patients who experienced no emetic episodes and moderate or severe nausea without rescue medication. The CR rate was defined as the proportion of patients experiencing no emesis without the use of rescue medication. The TC rate was defined as the proportion of patients experiencing no vomiting or nausea without the use of rescue medication. These parameters were evaluated during the first chemotherapy cycle. CC, complete control; CR, complete response; TC, total control
Secondary endpoints
The long-delayed CR and TC rates were 84.7% and 75.4%, respectively. CC, CR, and TC rates in the overall phase (0–336 h) were 75.6%, 84.3%, and 72.2%, respectively (Fig. 2a–c; Table 3). Risk factors for CINV among patients who did not achieve CC in the long-delayed phase included age (odds ratio 0.954 [95% confidence interval 0.909–0.998]), female sex (8.808 [2.446–41.992]), and a history of motion sickness (5.050 [1.118–27.548]) (Table 4). Time-to-treatment failure is shown in Fig. 3a–c.
Table 3.
Phase-specific control ratio over the extended overall phase (0–336 h)
| Acute phase (0–24 h) | |
| CC rate (%) | 81.0 |
| CR rate (%) | 87.0 |
| Delayed phase (24–120 h) | |
| CC rate (%) | 72.4 |
| CR rate (%) | 82.8 |
| Long delayed phase (120–336 h) | |
| CC rate (%) | 76.3 |
| CR rate (%) | 84.7 |
| TC rate (%) | 75.4 |
| Overall phase (0–336) | |
| CC rate (%) | 75.6 |
| CR rate (%) | 84.3 |
| TC rate (%) | 72.2 |
The CC rate was defined as the proportion of patients who experienced no emetic episodes and moderate or severe nausea without rescue medication. The CR rate was defined as the proportion of patients experiencing no emesis without the use of rescue medication. The TC rate was defined as the proportion of patients experiencing no vomiting or nausea without the use of rescue medication
Table 4.
Risk factors for CINV in patients who do not achieve CC in long-delayed phase
| P-value | OR | 95% CI | |
|---|---|---|---|
| Age | 0.020 | 0.954 | 0.909–0.998 |
| Sex (female) | < 0.01 | 8.808 | 2.446–41.992 |
| Alcohol consumption history (yes) | 0.162 | 0.447 | 0.14–1.34 |
| Motion sickness (yes) | 0.023 | 5.050 | 1.118–27.548 |
Logistic regression model was used for analysis
CC, complete control, defined as participants who experienced neither vomiting nor moderate-to-severe nausea and did not require rescue medication; OR, odds ratio; CI, confidence interval
Fig. 3.
(a) Time to treatment failure for CC; (b) Time to treatment failure in CR; (c) Time-to-treatment failure for TC. The CC rate was defined as the proportion of patients who experienced no emetic episodes and moderate or severe nausea without rescue medication. The CR rate was defined as the proportion of patients experiencing no emesis without rescue medication. The TC rate was defined as the proportion of patients experiencing no vomiting or nausea without rescue. CC, complete control; CR, complete response; TC, total control
Discussion
This study prospectively evaluated the long-delayed antiemetic efficacy of a triplet regimen involving FosNTP in patients receiving oxaliplatin-based chemotherapy. The regimen achieved a 76.3% CC rate in the long-delayed phase, which was the primary endpoint, and younger age, female sex, and a history of motion sickness were significant risk factors for inadequate control. To our knowledge, this is the first prospective study to assess the antiemetic efficacy of FosNTP during the extended long-delayed phase (120–336 h) in MEC, providing new clinical evidence for the prevention of long-delayed CINV.
At present, no studies have analyzed the efficacy of a FosNTP-containing triplet regimen for CINV in the long-delayed phase in patients receiving MEC regimens. To achieve more individualized and effective antiemetic management, clarifying both preventive efficacy of the triplet regimen across the extended overall phase (0–336 h) and factors associated with inadequate symptom control is essential. Given that patients receiving oxaliplatin-based chemotherapy are at particularly high risk for delayed-phase CINV, a detailed assessment of the true preventive effect of the triplet regimen was warranted. Differences between prospective and retrospective study designs [25, 26], as well as discrepancies between patient and clinician assessments particularly during the delayed phase [16], further supported the need for a prospective, patient-reported evaluation.
The observed 76.3% CC rate suggests that the regimen involving FosNTP maintained favorable antiemetic efficacy throughout the extended observation period. This efficacy is comparable to previously reported 80% control rates within 120 h for triplet regimens involving NK1RA with oxaliplatin-based chemotherapy [13, 14]. However, earlier studies did not evaluate outcomes beyond 120 h, leaving the persistence of antiemetic protection uncertain. In this context, our findings are noteworthy, given that several observational and meta-analytic studies have reported that some patients continue to experience nausea or vomiting beyond 120 h, even with standard prophylaxis [27]. Therefore, extending the observation window to 336 h enabled evaluation of the potential durability of the antiemetic activity of FosNTP into the long-delayed phase. Although this study lacks a concurrent comparator group, establishing a 336-hour benchmark is clinically vital for patients receiving oral fluoropyrimidine (capecitabine or S-1, tegafur/gimeracil/oteracil) for 14 consecutive days. Since capecitabine-induced nausea can continuously occur throughout the 2-week cycle, our data demonstrate that the triplet regimen provides sustained protection, which could be attributed to the long half-life of FosNTP. The observed prolonged control can be attributed to a long elimination half-life of approximately 144 h of FosNTP and sustained NK1 receptor occupancy (approximately 70% at 96 h and > 50% at 168 h) [23]. Clinically, these findings highlight the need for continued antiemetic protection beyond the conventional 5-day period in oxaliplatin-based regimens, particularly for patients at elevated emetic risk.
Despite these favorable results, the data indicate that additional improvement in long-delayed control may be necessary. Age, female sex, and motion sickness were identified as risk factors for failure to achieve CC in the long-delayed phase in the multivariable analysis. Female sex [28–32], young age [28, 29, 32, 33], little or no previous alcohol use [29, 31], a history of morning sickness during pregnancy [30], and motion sickness [30, 31, 34, 35] have been reported as risk factors for CINV. Consistent with prior studies, younger age, female sex, and motion sickness were associated with poorer long-delayed control, suggesting that additional therapy, including olanzapine, may be beneficial for patients with risk factors. As women are more likely than men to experience improved antiemetic effects with additional therapy [13], supplemental prophylaxis may be particularly useful in women to prevent anticipatory nausea.
Regarding CR rates in the delayed phase, a previous study reported that approximately 90% of patients achieved CR after receiving MEC with a FosNTP-containing antiemetic regimen [36]. These results demonstrate similarly favorable CR rates extending into the long-delayed phase.
However, opportunities for improvement remain for participants with high emetic risk factors, particularly in achieving CC and TC during the delayed phase. Future studies should evaluate antiemetic efficacy in patients with complex emetic risk factors and assess additional antiemetic agents for long-delayed control in high-risk patients. Recent randomized clinical trials have demonstrated that adding olanzapine to standard triple prophylaxis significantly improves TC rates in participants receiving MEC [37, 38]. However, as olanzapine is associated with sedation, appetite stimulation, and metabolic effects, continuous administration beyond the delayed phase is not practical. Therefore, short-term use during the early delayed phase or targeted use in selected high-risk patients may be reasonable; nonetheless, further studies are warranted to determine the optimal duration and timing of olanzapine for long-delayed CINV prevention.
These findings provide several clinically relevant implications for routine oncology practice. First, low-grade, persistent CINV during the second week of a chemotherapy cycle (120–336 h) represents a clinical blind spot in outpatient settings; patients often underreport these protracted symptoms once they return home. By prospectively utilizing patient-reported diaries, this study establishes a clear clinical benchmark for the extended long-delayed phase. Second, for patients undergoing the CapeOX or SOX regimen, which requires 14 consecutive days of oral fluoropyrimidine, these data provide clinicians with concrete figures to reassure patients during counseling. Clinicians can communicate that a single Day 1 dose of FosNTP provides a high probability of sustained protection (76.3% CC) throughout the entire 2-week treatment window, which may indirectly support treatment adherence. Finally, while the triplet regimen demonstrated robust durability, our results also highlight that approximately 24% of patients still experience insufficient emetic control during the second week. In current guidelines, the addition of a fourth agent, such as olanzapine, to moderately emetogenic regimens remains optional. The baseline data generated by the LODEC-N study provide a valuable clinical threshold to help identify which patient populations would benefit most from escalated, quadruple antiemetic strategies in future comparative trials.
This study has some limitations. First, it was a single-center, non-comparative study. Second, cancer types were limited to gastrointestinal cancers. Third, as this was not a randomized trial, improvements in outcomes could not be compared. Third, because this was a single-arm study without a concurrent control group, we cannot definitively rule out the possibility that the sustained control of CINV observed during the long-delayed phase partially reflects the natural decline in the emetogenic potential of oxaliplatin over time. Although the continuous administration of oral fluoropyrimidine for 14 days provides a sustained emetogenic stimulus and the long half-life of FosNTP (approximately 144 h) supports its prolonged pharmacological effect, the absence of a comparator group limits our ability to isolate the exact therapeutic contribution of FosNTP. Therefore, our efficacy results should be interpreted with caution, and future randomized controlled trials are required to confirm these observations. Finally, the long-term preventive efficacy of FosNTP in HEC regimens during the extended long-delayed phase remains unclear, as this study focused on oxaliplatin-based chemotherapy.
In conclusion, this prospective study suggests the potential efficacy and feasibility of a FosNTP -containing triplet antiemetic regimen in preventing CINV in participants receiving oxaliplatin-based chemotherapy, including during the long-delayed phase. However, participants with high emetic risk factors—such as younger age, female sex, or a history of motion sickness—continued to experience suboptimal control. These findings highlight the need for individualized antiemetic strategies and suggest that additional prophylactic agents, including olanzapine, may further improve outcomes in high-risk populations. Further prospective studies are warranted to determine the optimal combination and duration of antiemetic therapy for long-delayed CINV prevention.
Acknowledgements
We express our sincere gratitude to Dr. Ryo Ishida for providing valuable statistical advice and insightful comments during the preparation of this study. This study did not receive any specific grants from funding agencies in the public, commercial, or nonprofit sectors. This trial was conducted with an operating expense grant from our hospital.
Author contributions
Iimura Y wrote the main manuscript and prepared tables and figures. Y. Iimura conceived of the idea presented in this study. Kuroda and Iihara revised the study design. All the authors reviewed the manuscript.
Funding
Open Access funding provided by The University of Tokyo
Data availability
No datasets were generated or analysed during the current study.
Declarations
Competing interests
Hirotoshi Iihara served as a consultant for Astellas Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., and Taiho Pharmaceutical Co., Ltd. Hirotoshi Iihara received lecture fees from Astellas Pharma Co., Ltd.; AstraZeneca plc; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Eli Lilly and Company; Nippon Kayaku Co., Ltd.; Ohara Pharmaceutical Co., Ltd.; Sawai Pharmaceutical Co., Ltd.; Taiho Pharmaceutical Co., Ltd.; and Yakult Honsha Co., Ltd. Yohei Iimura, Takeshi Aoyama, Toshinobu Hayashi, Masaaki Ishibashi, Chieko Sasuga, Naoki Furukawa, Eri Anzai, Yuki Ijichi, and Seiichiro Kuroda have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Ethics approval and consent to participate
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethical Review Board of The Institute of Medical Science, the University of Tokyo (approval number: 2023-4-0420). This study was registered in the Japan Registry of Clinical Trials (jRCT) as jRCT1030230130. Written informed consent was obtained from all the patients.
Consent to participate
All patients provided written informed consent.
Consent to publish
Not applicable.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
No datasets were generated or analysed during the current study.