Research ArticleClinical Studies

Effect of Mirtazapine for the Prevention of Nausea and Vomiting in Patients With Thoracic Cancer Receiving Platinum-based Chemotherapy

MOTOHIKO KINOMURA, HIROTOSHI IIHARA, HIRONORI FUJII, CHIEMI HIROSE, JUNKI ENDO, KOMEI YANASE, TOSHIYA INUI, DAIZO KAITO, YUKA SASAKI, TAKENOBU GOMYO, CHIZURU SAKAI-MASUDA, DAISUKE KAWAE, YU KITAMURA, MASACHIKA FUKUI, RYO KOBAYASHI, YASUSHI OHNO and AKIO SUZUKI
Anticancer Research March 2023, 43 (3) 1301-1307; DOI: https://doi.org/10.21873/anticanres.16277

Abstract

Background/Aim: Mirtazapine, which exerts an antagonistic effect on 5-hydroxytryptamine type 5-HT2A, 5-HT2C, 5-HT3 and H1 receptors, is considered useful for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). This study investigated the efficacy and safety of mirtazapine for the prevention of CINV in patients with thoracic cancer receiving platinum-based chemotherapy. Patients and Methods: A retrospective cohort study was conducted in patients with thoracic cancer receiving platinum-based chemotherapy with 15 mg mirtazapine once daily as a prophylactic antiemetic drug between January 2014 and December 2021. The effects of mirtazapine added to the standard antiemetic regimen for the prevention of CINV were evaluated in patients who had poor control of CINV in a preceding cycle and in patients who received the standard antiemetic therapy plus mirtazapine from their first cycle. Results: A total of 35 patients were evaluated. Of these, 14 had poor control of CINV in a preceding cycle and received the standard antiemetic therapy plus mirtazapine in the next cycle. The rate of complete response in the delayed period in these patients was significantly improved from the preceding cycle to the next cycle (35.7% vs. 85.7%, p=0.018). In contrast, the other 21 patients had received the standard antiemetic regimen plus mirtazapine from the first cycle. The rate of complete response in the delayed period in these patients receiving the triplet antiemetic regimen plus mirtazapine as part of a cisplatin-based or carboplatin-based regimen and in patients receiving a doublet antiemetic regimen plus mirtazapine in a carboplatin-based regimen was 100%, 85.7% and 100%, respectively. No severe adverse events, including somnolence, were observed with the addition of mirtazapine. Conclusion: The addition of mirtazapine to the standard antiemetic regimen for CINV may be beneficial with acceptable safety when administered in association with platinum-based regimens to patients with thoracic cancer.

Key Words:

Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing problems affecting cancer patients receiving chemotherapy, and reduces their quality of life and adherence to treatment (1).

Chemotherapy based around platinum agents, such as cisplatin and carboplatin, is the standard treatment for thoracic cancer (2-9). The high emetic risk with cisplatin is well known. Although carboplatin was classified as having moderate emetic risk, several antiemetic guidelines have recently reclassified it as a high emetic risk agent because of its high emetogenic potential among the moderate emetic risk agents (10-12). For cisplatin-based chemotherapy, several international guidelines recommend a triplet antiemetic regimen consisting of 5-hydroxytryptamine type-3 (5-HT3) receptor antagonist combined with dexamethasone and neurokinin-1 receptor antagonists (NK1RA) for the prevention of CINV. A triplet antiemetic therapy regimen is also recommended for carboplatin, notwithstanding its different emetic risk profile compared to cisplatin. Nevertheless, antiemetic control is insufficient for both these platinum agent-based therapies, even with the recommended standard antiemetic therapy (10-12).

Several studies have reported a beneficial effect of adding olanzapine to standard antiemetic regimens, and some clinical guidelines now recommend it as an add-on regimen for patients with poor control of emesis (13-16). However, olanzapine induces adverse metabolic effects, as well as drowsiness and somnolence, and is not indicated in patients with diabetes mellitus and the elderly. A clinical need for new antiemetic agents therefore exists for patients with poor antiemetic control and difficulty using olanzapine.

Mirtazapine, a noradrenergic and specific serotonergic antidepressant, has multiple pharmacological actions, such as blocking postsynaptic 5-HT2A, 5-HT2C, 5-HT3, and H1 receptors, similarly to olanzapine, and has little anticholinergic activity. It is therefore expected to be as effective as olanzapine as an antiemetic (17, 18). Cau et al. reported that the addition of mirtazapine to a triplet antiemetic regimen is sufficient for the prevention of CINV in patients with breast cancer receiving highly emetogenic chemotherapy (19). Maleki et al. also found no substantial difference in prevention of CINV between mirtazapine and olanzapine when either was added to triple therapy in patients with breast cancer who had received combination chemotherapy with anthracycline plus cyclophosphamide (20). However, these studies were conducted in limited patient populations, and the antiemetic efficacy of mirtazapine in patients receiving platinum-based chemotherapy for thoracic cancer remains unclear.

Here, we retrospectively evaluated the efficacy and safety of mirtazapine when added to standard antiemetic therapy in patients with thoracic cancer receiving platinum-based chemotherapy.

Patients and Methods

Study design and patients. This study was conducted under a single-center, retrospective cohort design at Gifu University Hospital. Study participants included patients with thoracic cancer receiving platinum-containing chemotherapy with single daily administration of 15 mg mirtazapine as a prophylactic antiemetic drug between January 2014 and December 2021. Data were collected from electronic medical records in the central database of Gifu University Hospital.

Antiemetic regimen for prevention of CINV. Patients who received cisplatin-based chemotherapy were administered a triplet antiemetic regimen consisting of oral aprepitant (125 mg), intravenous 5-HT3 receptor antagonist (namely 0.75 mg palonosetron, 3 mg granisetron and 10 mg azasetron) and intravenous dexamethasone (9.9 mg) on day 1. Additionally, they were administered oral aprepitant (80 mg) on days 2-3, and intravenous (6.6 mg) or oral (4 mg) dexamethasone on days 2-4.

Patients who received carboplatin-based chemotherapy were treated with triplet or doublet antiemetic therapy. This difference is because the prophylactic antiemetic recommendations of several guidelines changed during the study period. The doublet antiemetic regimen consisted of intravenous 5-HT3 receptor antagonist as described above and intravenous dexamethasone (9.9 mg) on day 1. These patients additionally received intravenous (6.6 mg) or oral (4 mg) dexamethasone on days 2-3. The dose and duration of dexamethasone were adjusted at the discretion of the attending physician.

Mirtazapine was given by single daily administration at 15 mg after supper for 5 days from the initial day of administration of platinum-based regimens.

Evaluation of nausea and vomiting. The efficacy and safety of mirtazapine added to the standard antiemetic treatment were evaluated during the 5 days following administration of platinum-containing chemotherapy. Complete response (CR: no emesis and no rescue treatment), complete control (CC: no emesis, no rescue treatment, and no more than grade 1 nausea) and total control (TC: no emesis, no rescue treatment, and no nausea) were evaluated for the acute phase (within 24 hours post-chemotherapy), delayed phase (24-168 hours post-chemotherapy) and overall (0-168 hours post-chemotherapy).

Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 4.0, 2009 (National Cancer Institute, U.S. Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA) (21).

Statistical analysis. Data were analyzed using IBM SPSS Statistics ver. 22 (IBM Japan Services Co., Ltd., Tokyo, Japan). The chi-squared test or McNemar test were used to compare the two groups. p-Values of less than 0.05 were considered statistically significant.

Ethics statement. This study was carried out in accordance with the guidelines for human studies of the Ethics Committee of Gifu University Graduate School of Medicine, and was approved by the University’s Institutional Review Board (approval no. 2021-005). In view of the retrospective nature of the study, informed consent from the participants was not mandated. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Results

Patients. A total of 60 patients with thoracic cancer who received platinum-based chemotherapy during the study period were administrated mirtazapine as an antiemetic agent. Among them, 25 patients were excluded from the present analyses for the following reasons: Alteration of chemotherapy regimen during treatment in two patients; administration of mirtazapine only for purposes of rescue medication in 13; and additional administration of other antiemetic drugs to the standard antiemetic therapy in 10. Thus, the present analysis was conducted on data from 35 participants.

Patient demographics are shown in Table I. Most patients were male (71.4%) and the majority of patients median age was 69 years (range=47-81). The majority of patients had non-small cell lung cancer (82.9%). Cisplatin- and carboplatin-based chemotherapy was administered to 37.1% (13/35) and 62.9% (22/35), respectively.

View this table:
Table I.

Patient demographics.

Effects of the addition of mirtazapine to the standard antiemetic regimen in patients with poor control of CINV in preceding cycles. Among the 35 patients, 14 were administered mirtazapine in addition to the standard antiemetic regimen in the next cycle after poor control of CINV in a preceding cycle. Table II shows the standard antiemetic regimen given to these patients: 11 received a triplet antiemetic regimen, five for a cisplatin-based regimen and six for a carboplatin-based regimen; and three patients received a doublet antiemetic regimen for a carboplatin-based regimen.

View this table:
Table II.

Demographics of patients receiving mirtazapine added to a standard antiemetic regimen.

As shown in Figure 1, the rates of CR, CC and TC in the delayed phase of the next cycle were significantly higher than those of the preceding cycle, more than doubling. Similarly, the rates overall in the next cycle were higher than those in the preceding cycle, albeit without statistical significance in the rate of CR.

Figure 1.
Figure 1.

The rates of complete response (CR), complete control (CC) and total control (TC) in patients receiving mirtazapine (MTZ) added to a standard antiemetic regimen after poor control of chemotherapy-induced nausea and vomiting in preceding chemotherapy cycles.

There were no differences in the incidence of other adverse events between the preceding and next cycles (Table III).

View this table:
Table III.

Incidence of other adverse events in the preceding cycle of chemotherapy without mirtazapine and the next cycle with mirtazapine.

Control of CINV in patients who received the standard antiemetic therapy plus mirtazapine from their first chemotherapy cycle. The other 21 patients received the standard antiemetic therapy plus mirtazapine from their first cycle. Table II also shows the standard antiemetic regimen in these patients. Fifteen patients received a triplet antiemetic regimen for a cisplatin-based regimen (n=8) or carboplatin-based regimen (n=7), and six received doublet antiemetic regimen for a carboplatin-based regimen.

Figure 2 shows the rates of CR, CC, and TC in the acute, delayed, and overall phases. The rates of CR, CC, and TC in the delayed and overall periods were 100%, 87.5% and 87.5% and 100%, 87.5% and 87.5%, respectively, in the triplet regimen for the cisplatin-based regimen. Respective rates for the carboplatin-based regimen were 85.7%, 85.7% and 42.8% and 85.7%, 71.4% and 42.8% for the triplet regimen, and 100%, 100% and 67% and 100%, 100% and 67% for the doublet regimen.

Figure 2.
Figure 2.

The rates of complete response (CR), complete control (CC) and total control (TC) in patients receiving standard antiemetic therapy plus mirtazapine (MTZ) from their first chemotherapy cycle. CDDP: Cisplatin; CBDCA: carboplatin.

No severe adverse events including somnolence (data not shown), were observed.

Discussion

In this retrospective study, we revealed the efficacy and safety of mirtazapine added to the standard antiemetic regimen for the prevention of CINV in patients with thoracic cancer receiving platinum-containing chemotherapy. In patients who had poor control of CINV in a preceding cycle, addition of mirtazapine to the standard antiemetic medication in the next cycle significantly improved CR, CC and TC in the delayed phase and overall, albeit without statistical significance in CR overall. Cao et al. conducted a multicenter randomized phase III trial of patients with breast cancer receiving cisplatin-containing regimens or epirubicin plus cyclophosphamide who had experienced delayed emesis. They reported that, in subsequently scheduled chemotherapy, the rate of CR in the delayed phase when mirtazapine (15 mg daily on days 2-4) was added to the standard triple regimen was higher than that in the standard triple-regimen group (cisplatin-containing regimens: 85.7% vs. 52.4%, p=0.019; epirubicin plus cyclophosphamide: 72.0% vs. 46.4%, p=0.059) (19). Together, these findings suggest that the addition of mirtazapine to standard antiemetic therapy may be useful for improving the control of CINV in high-risk patients who had CINV in a previous chemotherapy cycle.

Moreover, we also observed a high CR rate in the delayed phase and overall in patients receiving mirtazapine added to the standard antiemetic triplet therapy of a cisplatin-based (delayed: 100%, overall: 100%) and carboplatin-based regimens (delayed: 85.7%, overall: 85.7%) in the first cycle and to the standard antiemetic doublet therapy of a carboplatin-based regimen (delayed: 100%, overall: 100%) in the first cycle. Similarly to olanzapine, mirtazapine has affinity for 5-HT2A, 5-HT3, and H1 receptors, which are involved in its antiemetic action (17, 18). Maleki et al. reported that the rate of CR in the delayed phase and overall in patients with breast cancer receiving an anthracycline plus cyclophosphamide regimen did not significantly differ between those receiving mirtazapine or olanzapine with the standard antiemetic doublet therapy from the first cycle (delayed: 80% vs. 86.6%, p=0.48; overall: 66.6% vs. 63.3%, p=0.78) (20). Additionally, in a prospective multicenter phase II trial of patients with thoracic malignancy receiving olanzapine plus granisetron and dexamethasone for carboplatin-induced nausea and vomiting, Sakai et al. reported that the rate of CR in the delayed phase and overall was 94.0% and 94.0%, respectively (14). These values are very similar to our present results. These findings may suggest that mirtazapine is a good alternative to olanzapine as a prophylactic antiemetic drug.

Of interest, we found that the rate of CR when mirtazapine was added to the standard antiemetic doublet therapy and triplet therapy was similar (delayed: 85.7% for triplet vs. 100% for doublet; overall: 85.7% for triplet vs. 100% for doublet). Yamamoto et al. reported an integrated analysis of three phase II studies that a prophylactic antiemetic combination regimen of olanzapine, 5-HT3 receptor antagonist and dexamethasone showed no significant difference in CR, CC, or TC rates between groups with and without added NK1RA (22), and noted that these results might have been attributable to patient characteristics: while younger age is a risk factor for CINV, the median age was a relatively old 71 years in both groups (23-28). In our present study, the median age was 69 years. These findings suggest that antiemetic regimens consisting of mirtazapine, 5-HT3 receptor antagonist and dexamethasone without NK1RA may be a treatment option for patients with thoracic cancer receiving platinum-based chemotherapy.

Compared to olanzapine, mirtazapine is reported to be better tolerated, cause less dizziness, and have less cardiovascular toxicity (29-31). Its lower rate of adverse effects such as somnolence is considered to be due to an anti-histamine effect which involves the enhancement of noradrenaline neurotransmission (17). A clinical trial demonstrated a lower frequency of somnolence and fatigue in the mirtazapine-treated than the olanzapine-treated group (20). In our study, additional administration of mirtazapine was not associated with significant adverse effects in elderly patients, including somnolence or drowsiness. We suggest that mirtazapine can be used safely in elderly patients in whom olanzapine is contraindicated due to concerns over adverse events.

There were several limitations in the present study. Firstly, it was conducted under a retrospective design, and potentially relevant confounding factors may not have been excluded. Secondly, the sample size was very small. Finally, the data were obtained from a single institution. Confirmation of the safety and efficacy of mirtazapine in the treatment of platinum-induced CINV awaits a large multicenter, prospective, randomized control study. In the future, a prospective interventional trial is warranted.

Conclusion

Allowing for its small sample size, this study suggests that the addition of mirtazapine to a standard antiemetic regimen may be beneficial, with acceptable safety, against CINV associated with platinum-based regimens in patients with thoracic cancer. In particular, mirtazapine may be a useful alternative for patients who have difficulty with olanzapine, such as diabetics and the elderly.

Acknowledgements

The Authors thank DMC Corp. (www.dmed.co.jp) for providing pre-submission English language editing of this article. This study did not receive funding from any funding source.

Footnotes

  • Authors’ Contributions

    M.K., H.I., H.F., C.H., R.K., and A.S. developed the study concept and design. M.K., H.I., R.K., and A.S. wrote the article. M.K., H.F., J.E., K.Y., T.I., D.K., Y.S. T.G., C. S-M., D.K., Y.K., and M.F. collected and assembled the data. M.K., H.I., H.F., and R.K. performed statistical analysis. Y.O. supervised the study. All Authors contributed to the article and approved the submitted version.

  • Conflicts of Interest

    All Authors declare they have no competing interests.

  • Received January 18, 2023.
  • Revision received January 30, 2023.
  • Accepted February 6, 2023.

References

  1. ↵
    1. Bloechl-Daum B,
    2. Deuson RR,
    3. Mavros P,
    4. Hansen M and
    5. Herrstedt J
    : Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol 24(27): 4472-4478, 2006. PMID: 16983116. DOI: 10.1200/JCO.2006.05.6382
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Wu YL,
    2. Planchard D,
    3. Lu S,
    4. Sun H,
    5. Yamamoto N,
    6. Kim DW,
    7. Tan DSW,
    8. Yang JC,
    9. Azrif M,
    10. Mitsudomi T,
    11. Park K,
    12. Soo RA,
    13. Chang JWC,
    14. Alip A,
    15. Peters S and
    16. Douillard JY
    : Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS. Ann Oncol 30(2): 171-210, 2019. PMID: 30596843. DOI: 10.1093/annonc/mdy554
    OpenUrlCrossRefPubMed
    1. Früh M,
    2. De Ruysscher D,
    3. Popat S,
    4. Crinò L,
    5. Peters S,
    6. Felip E and ESMO Guidelines Working Group
    : Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6): vi99-v105, 2013. PMID: 23813929. DOI: 10.1093/annonc/mdt178
    OpenUrlCrossRefPubMed
    1. Rudin CM,
    2. Ismaila N,
    3. Hann CL,
    4. Malhotra N,
    5. Movsas B,
    6. Norris K,
    7. Pietanza MC,
    8. Ramalingam SS,
    9. Turrisi AT 3rd. and
    10. Giaccone G
    : Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians Guideline. J Clin Oncol 33(34): 4106-4111, 2015. PMID: 26351333. DOI: 10.1200/JCO.2015.63.7918
    OpenUrlAbstract/FREE Full Text
    1. Hanna NH,
    2. Schneider BJ,
    3. Temin S,
    4. Baker S Jr.,
    5. Brahmer J,
    6. Ellis PM,
    7. Gaspar LE,
    8. Haddad RY,
    9. Hesketh PJ,
    10. Jain D,
    11. Jaiyesimi I,
    12. Johnson DH,
    13. Leighl NB,
    14. Phillips T,
    15. Riely GJ,
    16. Robinson AG,
    17. Rosell R,
    18. Schiller JH,
    19. Singh N,
    20. Spigel DR,
    21. Stabler JO,
    22. Tashbar J and
    23. Masters G
    : Therapy for stage IV non-small-cell lung cancer without driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol 38(14): 1608-1632, 2020. PMID: 31990617. DOI: 10.1200/JCO.19.03022
    OpenUrlCrossRefPubMed
    1. NCCN Clinical Practice Guidelines in Oncology
    : Non-Small Cell Lung Cancer. Version 6, 2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf [Last accessed December 12, 2022]
    1. NCCN Clinical Practice Guidelines in Oncology
    : Small Cell Lung Cancer. Version 2. 2023. Available at https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf [Last accessed December 12, 2022]
    1. NCCN Clinical Practice Guidelines in Oncology
    : Thymomas and Thymic Carcinomas. Version 2. 2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/thymic.pdf [Last accessed December 12, 2022]
  9. ↵
    1. NCCN Clinical Practice Guidelines in Oncology
    : Malignant Pleural Mesothelioma. Version 2. 2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf [Last accessed December 12, 2022]
  10. ↵
    1. Roila F,
    2. Molassiotis A,
    3. Herrstedt J,
    4. Aapro M,
    5. Gralla RJ,
    6. Bruera E,
    7. Clark-Snow RA,
    8. Dupuis LL,
    9. Einhorn LH,
    10. Feyer P,
    11. Hesketh PJ,
    12. Jordan K,
    13. Olver I,
    14. Rapoport BL,
    15. Roscoe J,
    16. Ruhlmann CH,
    17. Walsh D,
    18. Warr D,
    19. van der Wetering M and participants of the MASCC/ESMO Consensus Conference Copenhagen 2015
    : 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 27(Suppl 5): v119-v133, 2016. PMID: 27664248. DOI: 10.1093/annonc/mdw270
    OpenUrlCrossRefPubMed
    1. Hesketh PJ,
    2. Kris MG,
    3. Basch E,
    4. Bohlke K,
    5. Barbour SY,
    6. Clark-Snow RA,
    7. Danso MA,
    8. Dennis K,
    9. Dupuis LL,
    10. Dusetzina SB,
    11. Eng C,
    12. Feyer PC,
    13. Jordan K,
    14. Noonan K,
    15. Sparacio D and
    16. Lyman GH
    : Antiemetics: ASCO guideline update. J Clin Oncol 38(24): 2782-2797, 2020. PMID: 32658626. DOI: 10.1200/JCO.20.01296
    OpenUrlCrossRefPubMed
  12. ↵
    1. NCCN Clinical Practice Guidelines in Oncology
    : Antiemesis. Version 1. 2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf [Last accessed December 12, 2022]
  13. ↵
    1. Hashimoto H,
    2. Abe M,
    3. Tokuyama O,
    4. Mizutani H,
    5. Uchitomi Y,
    6. Yamaguchi T,
    7. Hoshina Y,
    8. Sakata Y,
    9. Takahashi TY,
    10. Nakashima K,
    11. Nakao M,
    12. Takei D,
    13. Zenda S,
    14. Mizukami K,
    15. Iwasa S,
    16. Sakurai M,
    17. Yamamoto N and
    18. Ohe Y
    : Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 21(2): 242-249, 2020. PMID: 31838011. DOI: 10.1016/S1470-2045(19)30678-3
    OpenUrlCrossRefPubMed
  14. ↵
    1. Sakai C,
    2. Shimokawa M,
    3. Iihara H,
    4. Fujita Y,
    5. Ikemura S,
    6. Hirose C,
    7. Kotake M,
    8. Funaguchi N,
    9. Gomyo T,
    10. Imai H,
    11. Hakamata J,
    12. Kaito D,
    13. Minato K,
    14. Arai T,
    15. Kawazoe H,
    16. Suzuki A,
    17. Ohno Y and
    18. Okura H
    : Low-dose olanzapine plus granisetron and dexamethasone for carboplatin-induced nausea and vomiting in patients with thoracic malignancies: a prospective multicenter phase II trial. Oncologist 26(6): e1066-e1072, 2021. PMID: 33811782. DOI: 10.1002/onco.13772
    OpenUrlCrossRefPubMed
    1. Iihara H,
    2. Shimokawa M,
    3. Hayasaki Y,
    4. Fujita Y,
    5. Abe M,
    6. Takenaka M,
    7. Yamamoto S,
    8. Arai T,
    9. Sakurai M,
    10. Mori M,
    11. Nakamura K,
    12. Kado N,
    13. Murase S,
    14. Shimaoka R,
    15. Suzuki A and
    16. Morishige KI
    : Efficacy and safety of 5 mg olanzapine combined with aprepitant, granisetron and dexamethasone to prevent carboplatin-induced nausea and vomiting in patients with gynecologic cancer: A multi-institution phase II study. Gynecol Oncol 156(3): 629-635, 2020. PMID: 31926638. DOI: 10.1016/j.ygyno.2020.01.004
    OpenUrlCrossRefPubMed
  16. ↵
    1. Tanaka K,
    2. Inui N,
    3. Karayama M,
    4. Yasui H,
    5. Hozumi H,
    6. Suzuki Y,
    7. Furuhashi K,
    8. Fujisawa T,
    9. Enomoto N,
    10. Nakamura Y,
    11. Kusagaya H,
    12. Matsuura S,
    13. Uto T,
    14. Hashimoto D,
    15. Matsui T,
    16. Asada K and
    17. Suda T
    : Olanzapine-containing antiemetic therapy for the prevention of carboplatin-induced nausea and vomiting. Cancer Chemother Pharmacol 84(1): 147-153, 2019. PMID: 31087137. DOI: 10.1007/s00280-019-03868-5
    OpenUrlCrossRefPubMed
  17. ↵
    1. Anttila SA and
    2. Leinonen EV
    : A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 7(3): 249-264, 2001. PMID: 11607047. DOI: 10.1111/j.1527-3458.2001.tb00198.x
    OpenUrlCrossRefPubMed
  18. ↵
    1. Fawcett J and
    2. Barkin RL
    : Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. J Affect Disord 51(3): 267-285, 1998. PMID: 10333982. DOI: 10.1016/s0165-0327(98)00224-9
    OpenUrlCrossRefPubMed
  19. ↵
    1. Cao J,
    2. Ouyang Q,
    3. Wang S,
    4. Ragaz J,
    5. Wang X,
    6. Teng Y,
    7. Wang B,
    8. Wang Z,
    9. Zhang J,
    10. Wang L,
    11. Wu J,
    12. Shao Z and
    13. Hu X
    : Mirtazapine, a dopamine receptor inhibitor, as a secondary prophylactic for delayed nausea and vomiting following highly emetogenic chemotherapy: an open label, randomized, multicenter phase III trial. Invest New Drugs 38(2): 507-514, 2020. PMID: 32036491. DOI: 10.1007/s10637-020-00903-8
    OpenUrlCrossRefPubMed
  20. ↵
    1. Maleki A,
    2. Ghadiyani M,
    3. Salamzadeh J,
    4. Salari S,
    5. Banihashem S and
    6. Tavakoli-Ardakani M
    : Comparison of mirtazapine and olanzapine on nausea and vomiting following anthracycline-cyclophosphamide chemotherapy regimen in patients with breast cancer. Iran J Pharm Res 19(3): 451-464, 2020. PMID: 33680044. DOI: 10.22037/ijpr.2020.113955.14584
    OpenUrlCrossRefPubMed
  21. ↵
    1. U.S. Department of Health and Human Services, National Institutes of Health National Cancer Institute
    , 2009. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Available at: https://www.eortc.be/services/doc/ctc/ [Last accessed on January 30, 2023]
  22. ↵
    1. Yamamoto S,
    2. Iihara H,
    3. Uozumi R,
    4. Kawazoe H,
    5. Tanaka K,
    6. Fujita Y,
    7. Abe M,
    8. Imai H,
    9. Karayama M,
    10. Hayasaki Y,
    11. Hirose C,
    12. Suda T,
    13. Nakamura K,
    14. Suzuki A,
    15. Ohno Y,
    16. Morishige KI and
    17. Inui N
    : Effects of adding a neurokinin-1 receptor antagonist to 5 mg olanzapine, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for preventing carboplatin-induced nausea and vomiting: a propensity score-matched analysis. BMC Cancer 22(1): 310, 2022. PMID: 35321690. DOI: 10.1186/s12885-022-09392-9
    OpenUrlCrossRefPubMed
  23. ↵
    1. Tamura K,
    2. Aiba K,
    3. Saeki T,
    4. Nakanishi Y,
    5. Kamura T,
    6. Baba H,
    7. Yoshida K,
    8. Yamamoto N,
    9. Kitagawa Y,
    10. Maehara Y,
    11. Shimokawa M,
    12. Hirata K,
    13. Kitajima M and CINV Study Group of Japan
    : Testing the effectiveness of antiemetic guidelines: results of a prospective registry by the CINV Study Group of Japan. Int J Clin Oncol 20(5): 855-865, 2015. PMID: 25681876. DOI: 10.1007/s10147-015-0786-7
    OpenUrlCrossRefPubMed
    1. Iihara H,
    2. Shimokawa M,
    3. Hayashi T,
    4. Kawazoe H,
    5. Saeki T,
    6. Aiba K and
    7. Tamura K
    : A nationwide, multicenter registry study of antiemesis for carboplatin-based chemotherapy-induced nausea and vomiting in Japan. Oncologist 25(2): e373-e380, 2020. PMID: 32043774. DOI: 10.1634/theoncologist.2019-0292
    OpenUrlCrossRefPubMed
    1. Nawa-Nishigaki M,
    2. Kobayashi R,
    3. Suzuki A,
    4. Hirose C,
    5. Matsuoka R,
    6. Mori R,
    7. Futamura M,
    8. Sugiyama T,
    9. Yoshida K and
    10. Itoh Y
    : Control of nausea and vomiting in patients receiving anthracycline/cyclophosphamide chemotherapy for breast cancer. Anticancer Res 38(2): 877-884, 2018. PMID: 29374715. DOI: 10.21873/anticanres.12297
    OpenUrlAbstract/FREE Full Text
    1. Hesketh PJ,
    2. Aapro M,
    3. Street JC and
    4. Carides AD
    : Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of two phase III trials of aprepitant in patients receiving cisplatin-based chemotherapy. Support Care Cancer 18(9): 1171-1177, 2010. PMID: 19756774. DOI: 10.1007/s00520-009-0737-9
    OpenUrlCrossRefPubMed
    1. Warr DG,
    2. Street JC and
    3. Carides AD
    : Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin-cyclophosphamide-based chemotherapy. Support Care Cancer 19(6): 807-813, 2011. PMID: 20461438. DOI: 10.1007/s00520-010-0899-5
    OpenUrlCrossRefPubMed
  28. ↵
    1. Suzuki A,
    2. Kobayashi R,
    3. Fujii H,
    4. Iihara H,
    5. Takahashi T,
    6. Yoshida K and
    7. Itoh Y
    : Control of nausea and vomiting in patients with colorectal cancer receiving chemotherapy with moderate emetic risk. Anticancer Res 36(12): 6527-6533, 2016. PMID: 27919978. DOI: 10.21873/anticanres.11254
    OpenUrlAbstract/FREE Full Text
  29. ↵
    1. de Boer T
    : The pharmacologic profile of mirtazapine. J Clin Psychiatry 57(Suppl 4): 19-25, 1996. PMID: 8636062.
    OpenUrlPubMed
    1. Nutt D
    : Mirtazapine: pharmacology in relation to adverse effects. Acta Psychiatr Scand Suppl 391: 31-37, 1997. PMID: 9265949. DOI: 10.1111/j.1600-0447.1997.tb05956.x
    OpenUrlCrossRefPubMed
  31. ↵
    1. Kast RE and
    2. Foley KF
    : Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects. Eur J Cancer Care (Engl) 16(4): 351-354, 2007. PMID: 17587360. DOI: 10.1111/j.1365-2354.2006.00760.x
    OpenUrlCrossRefPubMed
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Effect of Mirtazapine for the Prevention of Nausea and Vomiting in Patients With Thoracic Cancer Receiving Platinum-based Chemotherapy
MOTOHIKO KINOMURA, HIROTOSHI IIHARA, HIRONORI FUJII, CHIEMI HIROSE, JUNKI ENDO, KOMEI YANASE, TOSHIYA INUI, DAIZO KAITO, YUKA SASAKI, TAKENOBU GOMYO, CHIZURU SAKAI-MASUDA, DAISUKE KAWAE, YU KITAMURA, MASACHIKA FUKUI, RYO KOBAYASHI, YASUSHI OHNO, AKIO SUZUKI
Anticancer Research Mar 2023, 43 (3) 1301-1307; DOI: 10.21873/anticanres.16277
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