medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-179medsovet-7681Research ArticleПОДДЕРЖИВАЮЩАЯ ТЕРАПИЯSUPPORTIVE THERAPYВозможности профилактики тошноты при цитостатической терапии: обзор литературы и клиническое наблюдениеPossibilities of prevention of nausea during cytostatic therapy: literature review and clinical caseshttps://orcid.org/0000-0003-3734-2779МеньшиковК. В.MenshikovK. V.

Меньшиков Константин Викторович, к.м.н., врач-онколог отдела химиотерапии; доцент кафедры онкологии с курсами онкологии и патологической анатомии Института дополнительного профессионального образования

 450054, Россия, Уфа, проспект Октября, д. 73/1 

 450000, Россия, Уфа, ул. Ленина, д. 3 

Konstantin V. Menshikov, Cand. Sci. (Med.), Oncologist of the Chemotherapy Department; Associate Professor of the Department of Oncology with Courses in Oncology and Pathological Anatomy of the Institute of Additional Professional Education

73/1, Oktyabrya Ave., Ufa, 450054, Russia

3, Lenin St., Ufa, 450000, Russia 

kmenshikov80@bk.ruhttps://orcid.org/0000-0003-1185-977XМусинШ. И.MusinSh. I.

Мусин Шамиль Исмагилович, к.м.н., заведующий хирургическим отделением №6; доцент кафедры онкологии с курсами онкологии и патологической анатомии Института дополнительного профессионального образования 

 450054, Россия, Уфа, проспект Октября, д. 73/1 

 450000, Россия, Уфа, ул. Ленина, д. 3 

Shamil I. Musin, Cand. Sci. (Med.), Head of Surgical Department No. 6;  Associate Professor of the Department of Oncology with Courses in Oncology and Pathological Anatomy of the Institute of Additional Professional Education

73/1, Oktyabrya Ave., Ufa, 450054, Russia

3, Lenin St., Ufa, 450000, Russia 

musin_shamil@mail.ruhttps://orcid.org/0000-0003-0996-5995СултанбаевА. В.SultanbaevA. V.

Султанбаев Александр Валерьевич, к.м.н., заведующий отделом противоопухолевой лекарственной терапии

 450054, Россия, Уфа, проспект Октября, д. 73/1 

Alexander V. Sultanbaev, Cand. Sci. (Med.), Head of the Department of Anticancer Drug Therapy 

73/1, Oktyabrya Ave., Ufa, 450054, Russia 

rkodrb@yandex.ruhttps://orcid.org/0000-0001-8340-7962НасретдиновА. Ф.NasretdinovA. F.

Насретдинов Айнур Фанутович, врач-онколог, заведующий отделением противоопухолевой лекарственной терапии №2

 450054, Россия, Уфа, проспект Октября, д. 73/1 

Ainur F. Nasretdinov, Oncologist, Head of the Department of Antitumor Drug Therapy No. 2

73/1, Oktyabrya Ave., Ufa, 450054, Russia 

rkodrb@yandex.ruhttps://orcid.org/0000-0001-5926-0446СултанбаеваН. И.SultanbaevaN. I.

Султанбаева Надежда Ивановна, врач-онколог отделения противоопухолевой лекарственной терапии №1

 450054, Россия, Уфа, проспект Октября, д. 73/1 

Nadezda I. Sultanbaeva, Oncologist of the Department of Antitumor Drug Therapy No. 1

73/1, Oktyabrya Ave., Ufa, 450054, Russia 

nd.sultan@rambler.ruhttps://orcid.org/0000-0002-8665-8895МеньшиковаИ. А.MenshikovaI. A.

Меньшикова Ирина Асхатовна, к.м.н., доцент, доцент кафедры биологической химии

 450000, Россия, Уфа, ул. Ленина, д. 3 

Irina A. Menshikova, Cand. Sci. (Med.), Associate Professor of the Department of Biological Chemistry

3, Lenin St., Ufa, 450000, Russia 

i-menshikova@bk.ruhttps://orcid.org/0000-0002-6769-7194АюповР. Т.AyupovR. T.

Аюпов Рустем Талгатович, к.м.н., заместитель главного врача по медицинской части

 450054, Россия, Уфа, проспект Октября, д. 73/1 

Rustam T. Ayupov, Cand. Sci. (Med.), Deputy Chief Physician for Medical Affairs

73/1, Oktyabrya Ave., Ufa, 450054, Russia 

ru2003@bk.ruhttps://orcid.org/0000-0002-8461-9243ИзмайловА. А.IzmailovA. A.

Измайлов Адель Альбертович, д.м.н., главный врач

 450054, Россия, Уфа, проспект Октября, д. 73/1 

Adel A. Izmailov, Dr. Sci. (Med.), Chief Medical Officer 

73/1, Oktyabrya Ave., Ufa, 450054, Russia 

izmailov75@mail.ruРеспубликанский клинический онкологический диспансер; Башкирский государственный медицинский университетРоссияRepublican Clinical Oncological Dispensary; Bashkir State Medical UniversityRussian FederationРеспубликанский клинический онкологический диспансерРоссияRepublican Clinical Oncological DispensaryRussian FederationБашкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian Federation2023270720230116574Copyright © Меньшиков К.В., Мусин Ш.И., Султанбаев А.В., Насретдинов А.Ф., Султанбаева Н.И., Меньшикова И.А., Аюпов Р.Т., Измайлов А.А., 20232023Меньшиков К.В., Мусин Ш.И., Султанбаев А.В., Насретдинов А.Ф., Султанбаева Н.И., Меньшикова И.А., Аюпов Р.Т., Измайлов А.А.Menshikov K.V., Musin S.I., Sultanbaev A.V., Nasretdinov A.F., Sultanbaeva N.I., Menshikova I.A., Ayupov R.T., Izmailov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7681

Тошнота и рвота, вызванные химиотерапией, являются побочным эффектом лечения злокачественных новообразований, поражающим до 40% пациентов. Тошнота и рвота являются наиболее опасными, а также самыми распространенными побочными эффектами среди пациентов, проходящих химиотерапию. Синдром CINV остается одним из наиболее тревожных синдромов, связанных с терапией рака, и может привести к обезвоживанию, электролитному дисбалансу, недоеданию и нарушениям обмена веществ. Факторы риска развития CINV включают пол и возраст пациента, наличие CINV в анамнезе, а также эметогенность и график проведения химиотерапии. Вариантами профилактики CINV являются антагонисты 5-HT3-рецепторов (например, ондансетрон, гранисетрон, палоносетрон) в комбинации с кортикостероидами (например, дексаметазон) или дополнительно в сочетании с антагонистами рецепторов NK1 (например, апрепитант, фосапрепитант, нетупитант, ролапитант). Палоносетрон представляет собой селективный антагонист 5-HT3-рецепторов. Эффективность палоносетрона при отсроченной тошноте и рвоте также подтверждается результатами трех рандомизированных исследований, которые продемонстрировали отсутствие побочных эффектов упрощенного режима с палоносетроном и однократной дозой дексаметазона для контроля CINV, связанного со среднеэметогенной химиотерапией или режимом AC. Приведено клиническое наблюдение лечения пациентки молодого возраста по поводу рака молочной железы. У пациентки после первого курса химиотерапии развилось достаточно серьезное осложнение в виде рвоты, что потребовало госпитализации в стационар для проведения инфузионной терапии. Приведенное клиническое наблюдение демонстрирует эффективность палоносетрона в неоадъювантной химиотерапии у молодой пациентки, что позволило завершить весь курс лечения. После завершения неоадъювантной химиотерапии произведена радикальная операция и констатирован полный морфологический ответ.

Chemotherapy-induced nausea and vomiting (CINV) is a side effect of cancer treatment, affecting up to 40% of patients. Nausea and vomiting are the most dangerous and also the most common side effects among patients undergoing chemotherapy. CINV remains one of the most worrisome syndromes associated with cancer therapy and can lead to dehydration, electrolyte imbalances, malnutrition, and metabolic disorders. Risk factors for developing CINV include the patient’s gender and age, a history of CINV, and the emetogenicity and timing of chemotherapy. Options for preventing CINV are 5-HT3 receptor antagonists (i.e., ondansetron, granisetron, palonosetron) in combination with corticosteroids (i.e., dexamethasone) or additionally in combination with NK1 receptor antagonists (i.e., aprepitant, fosaprepitant, netupitant, rolapitant). Palonosetron is a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The effectiveness of palonosetron for delayed nausea and vomiting is also supported by the results of three randomized trials that demonstrated no side effects of the simplified regimen with palonosetron and single dose dexamethasone for the control of CINV associated with moderately emetogenic chemotherapy or AC regimen. A clinical observation of the treatment of a young patient with breast cancer is given. After the first course of chemotherapy, the patient developed a rather serious complication in the form of vomiting, which required hospitalization for infusion therapy. The above clinical observation demonstrates the effectiveness of palonosetron in neo-adjuvant chemotherapy in a young patient, which made it possible to complete the entire course of treatment. After completion of neo-adjuvant chemotherapy, a radical operation was performed and a complete morphological response was noted.

тошнотарвотаантиэметогенная терапияцитостатикиракпалоносетрон5-НТ3-рецепторnauseavomitanti-emitogenic therapycytostaticscancerpalonosetron5-HT3 receptorReferencesFeyer P., Jordan K. Update and new trends in antiemetic therapy: the continuing need for novel therapies. Ann Oncol. 2011;22(1):30–38. https://doi.org/10.1093/annonc/mdq600.Feyer P., Jordan K. Update and new trends in antiemetic therapy: the continuing need for novel therapies. Ann Oncol. 2011;22(1):30–38. https://doi.org/10.1093/annonc/mdq600.Jordan K., Chan A., Gralla R.J., Jahn F., Rapoport B., Warr D., Hesketh P.J. 2016 Updated MASCC/ESMO consensus recommendations: Emetic risk classification and evaluation of the emetogenicity of antineoplastic agents. Support Care Cancer. 2017;25(1):271–275. https://doi.org/10.1007/s00520-016-3332-x.Jordan K., Chan A., Gralla R.J., Jahn F., Rapoport B., Warr D., Hesketh P.J. 2016 Updated MASCC/ESMO consensus recommendations: Emetic risk classification and evaluation of the emetogenicity of antineoplastic agents. Support Care Cancer. 2017;25(1):271–275. https://doi.org/10.1007/s00520-016-3332-x.Howlader N., Noone A.M., Krapcho M., Garshell J., Neyman N., Altekruse S.F. et al. (eds.). SEER Cancer Statistics Review, 1975–2010. Bethesda, MD: National Cancer Institute; 2013. Available at: https://seer.cancer.gov/archive/csr/1975_2010/.Howlader N., Noone A.M., Krapcho M., Garshell J., Neyman N., Altekruse S.F. et al. (eds.). SEER Cancer Statistics Review, 1975–2010. Bethesda, MD: National Cancer Institute; 2013. Available at: https://seer.cancer.gov/archive/csr/1975_2010/.Navari R.M., Aapro M. Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016;374(14):1356–1367. https://doi.org/10.1056/NEJMra1515442.Navari R.M., Aapro M. Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016;374(14):1356–1367. https://doi.org/10.1056/NEJMra1515442.Tageja N., Groninger H. Chemotherapy-induced nausea and vomiting: an overview and comparison of three consensus guidelines. Postgrad Med J. 2016;92(1083):34–40. https://doi.org/10.1136/postgradmedj-2014-132969.Tageja N., Groninger H. Chemotherapy-induced nausea and vomiting: an overview and comparison of three consensus guidelines. Postgrad Med J. 2016;92(1083):34–40. https://doi.org/10.1136/postgradmedj-2014-132969.Di Mattei V.E., Carnelli L., Carrara L., Bernardi M., Crespi G., Rancoita P.M.V. et al. Chemotherapy-Induced Nausea and Vomiting in Women With Gynecological Cancer: A Preliminary Single-Center Study Investigating Medical and Psychosocial Risk Factors. Cancer Nurs. 2016;39(6):E52–E59. https://doi.org/10.1097/NCC.0000000000000342.Di Mattei V.E., Carnelli L., Carrara L., Bernardi M., Crespi G., Rancoita P.M.V. et al. Chemotherapy-Induced Nausea and Vomiting in Women With Gynecological Cancer: A Preliminary Single-Center Study Investigating Medical and Psychosocial Risk Factors. Cancer Nurs. 2016;39(6):E52–E59. https://doi.org/10.1097/NCC.0000000000000342.Dranitsaris G., Molassiotis A., Clemons M., Roeland E., Schwartzberg L., Dielenseger P. et al. The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting. Ann Oncol. 2017;28(6):1260–1267. https://doi.org/10.1093/annonc/mdx100.Dranitsaris G., Molassiotis A., Clemons M., Roeland E., Schwartzberg L., Dielenseger P. et al. The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting. Ann Oncol. 2017;28(6):1260–1267. https://doi.org/10.1093/annonc/mdx100.Furukawa N., Akasaka J., Shigemitsu A., Sasaki Y., Nagai A., Kawaguchi R., Kobayashi H. Evaluation of the relation between patient characteristics and the state of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer receiving paclitaxel and carboplatin. Arch Gynecol Obstet. 2014;289(4):859–864. https://doi.org/10.1007/s00404-013-3058-7.Furukawa N., Akasaka J., Shigemitsu A., Sasaki Y., Nagai A., Kawaguchi R., Kobayashi H. Evaluation of the relation between patient characteristics and the state of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer receiving paclitaxel and carboplatin. Arch Gynecol Obstet. 2014;289(4):859–864. https://doi.org/10.1007/s00404-013-3058-7.Hu Z., Liang W., Yang Y., Keefe D., Ma Y., Zhao Y. et al. Personalized Estimate of Chemotherapy-Induced Nausea and Vomiting: Development and External Validation of a Nomogram in Cancer Patients Receiving Highly/ Moderately Emetogenic Chemotherapy. Medicine (Baltimore). 2016;95(2):e2476. https://doi.org/10.1097/MD.0000000000002476.Hu Z., Liang W., Yang Y., Keefe D., Ma Y., Zhao Y. et al. Personalized Estimate of Chemotherapy-Induced Nausea and Vomiting: Development and External Validation of a Nomogram in Cancer Patients Receiving Highly/ Moderately Emetogenic Chemotherapy. Medicine (Baltimore). 2016;95(2):e2476. https://doi.org/10.1097/MD.0000000000002476.Warr D. Prognostic factors for chemotherapy induced nausea and vomiting. Eur J Pharmacol. 2014;722:192–196. https://doi.org/10.1016/j.ejphar.2013.10.015.Warr D. Prognostic factors for chemotherapy induced nausea and vomiting. Eur J Pharmacol. 2014;722:192–196. https://doi.org/10.1016/j.ejphar.2013.10.015.Hesketh P.J., Aapro M., Street J.C., Carides A.D. 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. 2010;18(9):1171–1177. https://doi.org/10.1007/s00520-009-0737-9.Hesketh P.J., Aapro M., Street J.C., Carides A.D. 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. 2010;18(9):1171–1177. https://doi.org/10.1007/s00520-009-0737-9.Viale P.H., Grande C., Moore S. Efficacy and cost: avoiding undertreatment of chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs. 2012;16(4):E133–141. https://doi.org/10.1188/12.CJON.E133-E141.Viale P.H., Grande C., Moore S. Efficacy and cost: avoiding undertreatment of chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs. 2012;16(4):E133–141. https://doi.org/10.1188/12.CJON.E133-E141.Wozniak A.J., Crowley J.J., Balcerzak S.P., Weiss G.R., Spiridonidis C.H., Baker L.H. et al. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998;16(7):2459–2465. https://doi.org/10.1200/JCO.1998.16.7.2459.Wozniak A.J., Crowley J.J., Balcerzak S.P., Weiss G.R., Spiridonidis C.H., Baker L.H. et al. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998;16(7):2459–2465. https://doi.org/10.1200/JCO.1998.16.7.2459.Basch E., Prestrud A.A., Hesketh P.J., Kris M.G., Somerfield M.R., Lyman G.H. Antiemetic Use in Oncology: Updated Guideline Recommendations from ASCO. Am Soc Clin Oncol Educ Book. 2012:32:532–540. https://doi.org/10.14694/EdBook_AM.2012.32.230.Basch E., Prestrud A.A., Hesketh P.J., Kris M.G., Somerfield M.R., Lyman G.H. Antiemetic Use in Oncology: Updated Guideline Recommendations from ASCO. Am Soc Clin Oncol Educ Book. 2012:32:532–540. https://doi.org/10.14694/EdBook_AM.2012.32.230.Roila F., Molassiotis A., Herrstedt J., Aapro M., Gralla R.J., Bruera E. et al. 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. 2016;27(Suppl. 5): v119–v133. https://doi.org/10.1093/annonc/mdw270.Roila F., Molassiotis A., Herrstedt J., Aapro M., Gralla R.J., Bruera E. et al. 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. 2016;27(Suppl. 5): v119–v133. https://doi.org/10.1093/annonc/mdw270.Hesketh P.J., Bohlke K., Lyman G.H., Basch E., Chesney M., Clark-Snow R.A. et al. Antiemetics: American Society of Clinical Oncology Focused Guideline Update. J Clin Oncol. 2016;34(4):381–386. https://doi.org/10.1200/JCO.2015.64.3635.Hesketh P.J., Bohlke K., Lyman G.H., Basch E., Chesney M., Clark-Snow R.A. et al. Antiemetics: American Society of Clinical Oncology Focused Guideline Update. J Clin Oncol. 2016;34(4):381–386. https://doi.org/10.1200/JCO.2015.64.3635.Shimokawa M., Haratake N., Takada K., Toyokawa G., Takamori S., Mizuki F. et al. Combination Antiemetic Therapy for Chemotherapy-Induced Nausea and Vomiting in Patients with NSCLC Receiving Carboplatin-Based Chemotherapy. Cancer Manag Res. 2022;14:2673–2680. https://doi.org/10.2147/CMAR.S370961.Shimokawa M., Haratake N., Takada K., Toyokawa G., Takamori S., Mizuki F. et al. Combination Antiemetic Therapy for Chemotherapy-Induced Nausea and Vomiting in Patients with NSCLC Receiving Carboplatin-Based Chemotherapy. Cancer Manag Res. 2022;14:2673–2680. https://doi.org/10.2147/CMAR.S370961.Siddiqui M.A., Scott L.J. Palonosetron. Drugs. 2004;64(10):1125–1132. https://doi.org/10.2165/00003495-200464100-00006.Siddiqui M.A., Scott L.J. Palonosetron. Drugs. 2004;64(10):1125–1132. https://doi.org/10.2165/00003495-200464100-00006.Yang L.P., Scott L.J. Palonosetron: in the prevention of nausea and vomiting. Drugs. 2009;69(16):2257–2278. https://doi.org/10.2165/11200980-000000000-00000.Yang L.P., Scott L.J. Palonosetron: in the prevention of nausea and vomiting. Drugs. 2009;69(16):2257–2278. https://doi.org/10.2165/11200980-000000000-00000.Popovic M., Warr D.G., Deangelis C., Tsao M., Chan K.K., Poon M. et al. Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer. 2014;22(6):1685–1697. https://doi.org/10.1007/s00520-014-2175-6.Popovic M., Warr D.G., Deangelis C., Tsao M., Chan K.K., Poon M. et al. Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer. 2014;22(6):1685–1697. https://doi.org/10.1007/s00520-014-2175-6.Hashimoto H., Yamanaka T., Shimada Y., Arata K., Matsui R., Goto K. et al. Palonosetron (PALO) versus granisetron (GRA) in the triplet regimen with dexamethasone (DEX) and aprepitant (APR) for preventing chemotherapyinduced nausea and vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC) with cisplatin (CDDP): A randomized, double-blind, phase III trial. J Clin Oncol. 2013;31(Suppl. 15):9621–9621. https://doi.org/10.1200/jco.2013.31.15_suppl.9621.Hashimoto H., Yamanaka T., Shimada Y., Arata K., Matsui R., Goto K. et al. Palonosetron (PALO) versus granisetron (GRA) in the triplet regimen with dexamethasone (DEX) and aprepitant (APR) for preventing chemotherapyinduced nausea and vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC) with cisplatin (CDDP): A randomized, double-blind, phase III trial. J Clin Oncol. 2013;31(Suppl. 15):9621–9621. https://doi.org/10.1200/jco.2013.31.15_suppl.9621.Navari R.M., Gray S.E., Kerr A.C. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011;9(5):188–195. https://doi.org/10.1016/j.suponc.2011.05.002.Navari R.M., Gray S.E., Kerr A.C. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011;9(5):188–195. https://doi.org/10.1016/j.suponc.2011.05.002.Hesketh P.J., Rossi G., Rizzi G., Palmas M., Alyasova A., Bondarenko I. et al. Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol. 2014;25(7):1340–1346. https://doi.org/10.1093/annonc/mdu110.Hesketh P.J., Rossi G., Rizzi G., Palmas M., Alyasova A., Bondarenko I. et al. Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol. 2014;25(7):1340–1346. https://doi.org/10.1093/annonc/mdu110.Roila F., Ruggeri B., Ballatori E., Fatigoni S., Caserta C., Licitra L. et al. Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study. Ann Oncol. 2015;26(6):1248–1253. https://doi.org/10.1093/annonc/mdv132.Roila F., Ruggeri B., Ballatori E., Fatigoni S., Caserta C., Licitra L. et al. Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study. Ann Oncol. 2015;26(6):1248–1253. https://doi.org/10.1093/annonc/mdv132.Aapro M., Rugo H., Rossi G., Rizzi G., Borroni M.E., Bondarenko I. et al. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapyinduced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014;25(7):1328–1333. https://doi.org/10.1093/annonc/mdu101.Aapro M., Rugo H., Rossi G., Rizzi G., Borroni M.E., Bondarenko I. et al. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapyinduced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014;25(7):1328–1333. https://doi.org/10.1093/annonc/mdu101.Roila F., Ruggeri B., Ballatori E., Del Favero A., Tonato M. Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol. 2014;32(2):101–106. https://doi.org/10.1200/JCO.2013.51.4547.Roila F., Ruggeri B., Ballatori E., Del Favero A., Tonato M. Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol. 2014;32(2):101–106. https://doi.org/10.1200/JCO.2013.51.4547.Matsumoto K., Takahashi M., Sato K., Osaki A., Takano T., Naito Y. et al. A doubleblind, randomized, multicenter phase 3 study of palonosetron vs granisetron combined with dexamethasone and fosaprepitant to prevent chemotherapyinduced nausea and vomiting in patients with breast cancer receiving anthracycline and cyclophosphamide. Cancer Med. 2020;9(10):3319–3327. https://doi.org/10.1002/cam4.2979.Matsumoto K., Takahashi M., Sato K., Osaki A., Takano T., Naito Y. et al. A doubleblind, randomized, multicenter phase 3 study of palonosetron vs granisetron combined with dexamethasone and fosaprepitant to prevent chemotherapyinduced nausea and vomiting in patients with breast cancer receiving anthracycline and cyclophosphamide. Cancer Med. 2020;9(10):3319–3327. https://doi.org/10.1002/cam4.2979.Aapro M., Fabi A., Nolè F., Medici M., Steger G., Bachmann C. et al. Doubleblind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol. 2010;21(5):1083–1088. https://doi.org/10.1093/annonc/mdp584.Aapro M., Fabi A., Nolè F., Medici M., Steger G., Bachmann C. et al. Doubleblind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol. 2010;21(5):1083–1088. https://doi.org/10.1093/annonc/mdp584.Celio L., Frustaci S., Denaro A., Buonadonna A., Ardizzoia A., Piazza E. et al. Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial. Support Care Cancer. 2011;19(8):1217–1225. https://doi.org/10.1007/s00520-010-0941-7.Celio L., Frustaci S., Denaro A., Buonadonna A., Ardizzoia A., Piazza E. et al. Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial. Support Care Cancer. 2011;19(8):1217–1225. https://doi.org/10.1007/s00520-010-0941-7.Komatsu Y., Okita K., Yuki S., Furuhata T., Fukushima H., Masuko H. et al. Openlabel, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron. Cancer Sci. 2015;106(7):891–895. https://doi.org/10.1111/cas.12675.Komatsu Y., Okita K., Yuki S., Furuhata T., Fukushima H., Masuko H. et al. Openlabel, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron. Cancer Sci. 2015;106(7):891–895. https://doi.org/10.1111/cas.12675.Celio L., Niger M., Ricchini F., Agustoni F. Palonosetron in the prevention of chemotherapy-induced nausea and vomiting: an evidence-based review of safety, efficacy, and place in therapy. Core Evid. 2015;10:75–87. https://doi.org/10.2147/CE.S65555.Celio L., Niger M., Ricchini F., Agustoni F. Palonosetron in the prevention of chemotherapy-induced nausea and vomiting: an evidence-based review of safety, efficacy, and place in therapy. Core Evid. 2015;10:75–87. https://doi.org/10.2147/CE.S65555.Wenzell C.M., Berger M.J., Blazer M.A., Crawford B.S., Griffith N.L., Wesolowski R. et al. Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy. Support Care Cancer. 2013;21(10):2845–2851. https://doi.org/10.1007/s00520-013-1865-9.Wenzell C.M., Berger M.J., Blazer M.A., Crawford B.S., Griffith N.L., Wesolowski R. et al. Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy. Support Care Cancer. 2013;21(10):2845–2851. https://doi.org/10.1007/s00520-013-1865-9.Roila F., Herrstedt J., Aapro M., Gralla R.J., Einhorn L.H., Ballatori E. et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010;21(Suppl. 5):v232–243. https://doi.org/10.1093/annonc/mdq194.Roila F., Herrstedt J., Aapro M., Gralla R.J., Einhorn L.H., Ballatori E. et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010;21(Suppl. 5):v232–243. https://doi.org/10.1093/annonc/mdq194.Hesketh P.J., Kris M.G., Basch E., Bohlke K., Barbour S.Y., Clark-Snow R.A. et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017;35(28):3240–3261. https://doi.org/10.1200/JCO.2017.74.4789.Hesketh P.J., Kris M.G., Basch E., Bohlke K., Barbour S.Y., Clark-Snow R.A. et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017;35(28):3240–3261. https://doi.org/10.1200/JCO.2017.74.4789.Navari R.M. Management of chemotherapy-induced nausea and vomiting: focus on newer agents and new uses for older agents. Drugs. 2013;73(3):249–262. https://doi.org/10.1007/s40265-013-0019-1.Navari R.M. Management of chemotherapy-induced nausea and vomiting: focus on newer agents and new uses for older agents. Drugs. 2013;73(3):249–262. https://doi.org/10.1007/s40265-013-0019-1.Saito M., Aogi K., Sekine I., Yoshizawa H., Yanagita Y., Sakai H. et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a doubleblind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 2009;10(2):115–124. https://doi.org/10.1016/S1470-2045(08)70313-9.Saito M., Aogi K., Sekine I., Yoshizawa H., Yanagita Y., Sakai H. et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a doubleblind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 2009;10(2):115–124. https://doi.org/10.1016/S1470-2045(08)70313-9.Rojas C., Stathis M., Thomas A.G., Massuda E.B., Alt J., Zhang J. et al. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg. 2008;107(2):469–478. https://doi.org/10.1213/ane.0b013e318172fa74.Rojas C., Stathis M., Thomas A.G., Massuda E.B., Alt J., Zhang J. et al. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg. 2008;107(2):469–478. https://doi.org/10.1213/ane.0b013e318172fa74.Rojas C., Thomas A.G., Alt J., Stathis M., Zhang J., Rubenstein E.B. et al. Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol. 2010;626(2-3):193–199. https://doi.org/10.1016/j.ejphar.2009.10.002.Rojas C., Thomas A.G., Alt J., Stathis M., Zhang J., Rubenstein E.B. et al. Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol. 2010;626(2-3):193–199. https://doi.org/10.1016/j.ejphar.2009.10.002.Rojas C., Li Y., Zhang J., Stathis M., Alt J., Thomas A.G. et al. The antiemetic 5-HT3 receptor antagonist Palonosetron inhibits substance P-mediated responses in vitro and in vivo. J Pharmacol Exp Ther. 2010;335(2):362–368. https://doi.org/10.1124/jpet.110.166181.Rojas C., Li Y., Zhang J., Stathis M., Alt J., Thomas A.G. et al. The antiemetic 5-HT3 receptor antagonist Palonosetron inhibits substance P-mediated responses in vitro and in vivo. J Pharmacol Exp Ther. 2010;335(2):362–368. https://doi.org/10.1124/jpet.110.166181.Schwartzberg L. Addressing the value of novel therapies in chemotherapyinduced nausea and vomiting. Expert Rev Pharmacoecon Outcomes Res. 2014;14(6):825–834. https://doi.org/10.1586/14737167.2014.957683.Schwartzberg L. Addressing the value of novel therapies in chemotherapyinduced nausea and vomiting. Expert Rev Pharmacoecon Outcomes Res. 2014;14(6):825–834. https://doi.org/10.1586/14737167.2014.957683.Curigliano G., Burstein H.J., Winer E.P., Gnant M., Dubsky P., Loibl S. et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28(8):1700–1712. https://doi.org/10.1093/annonc/mdx308.Curigliano G., Burstein H.J., Winer E.P., Gnant M., Dubsky P., Loibl S. et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28(8):1700–1712. https://doi.org/10.1093/annonc/mdx308.Allevi G., Strina C., Andreis D., Zanoni V., Bazzola L., Bonardi S. et al. Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer. Br J Cancer. 2013;108(8):1587–1592. https://doi.org/10.1038/bjc.2013.151.Allevi G., Strina C., Andreis D., Zanoni V., Bazzola L., Bonardi S. et al. Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer. Br J Cancer. 2013;108(8):1587–1592. https://doi.org/10.1038/bjc.2013.151.Schneeweiss A., Chia S., Hickish T., Harvey V., Eniu A., Hegg R. et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278–2284. https://doi.org/10.1093/annonc/mdt182.Schneeweiss A., Chia S., Hickish T., Harvey V., Eniu A., Hegg R. et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278–2284. https://doi.org/10.1093/annonc/mdt182.Hussain N., Said A.S.A., Khan Z. Safety Assessment of Neoadjuvant Pertuzumab Combined with Trastuzumab in Nonmetastatic HER2-Positive Breast Cancer in Postmenopausal Elderly Women of South Asia. Int J Breast Cancer. 2018:6106041. https://doi.org/10.1155/2018/6106041.Hussain N., Said A.S.A., Khan Z. Safety Assessment of Neoadjuvant Pertuzumab Combined with Trastuzumab in Nonmetastatic HER2-Positive Breast Cancer in Postmenopausal Elderly Women of South Asia. Int J Breast Cancer. 2018:6106041. https://doi.org/10.1155/2018/6106041.Lorusso D., Bria E., Costantini A., Di Maio M., Rosti G., Mancuso A. Patients’ perception of chemotherapy side effects: Expectations, doctor-patient communication and impact on quality of life – An Italian survey. Eur J Cancer Care (Engl). 2017;26(2). https://doi.org/10.1111/ecc.12618.Lorusso D., Bria E., Costantini A., Di Maio M., Rosti G., Mancuso A. Patients’ perception of chemotherapy side effects: Expectations, doctor-patient communication and impact on quality of life – An Italian survey. Eur J Cancer Care (Engl). 2017;26(2). https://doi.org/10.1111/ecc.12618.Grunberg S.M., Deuson R.R., Mavros P., Geling O., Hansen M., Cruciani G. et al. Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer. 2004;100(10):2261–2268. https://doi.org/10.1002/cncr.20230.Grunberg S.M., Deuson R.R., Mavros P., Geling O., Hansen M., Cruciani G. et al. Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer. 2004;100(10):2261–2268. https://doi.org/10.1002/cncr.20230.Aapro M., Ruffo P., Panteri R., Costa S., Piovesana V. Oncologist perspectives on chemotherapy-induced nausea and vomiting (CINV) management and outcomes: A quantitative market research-based survey. Cancer Rep (Hoboken). 2018;1(4):e1127. https://doi.org/10.1002/cnr2.1127.Aapro M., Ruffo P., Panteri R., Costa S., Piovesana V. Oncologist perspectives on chemotherapy-induced nausea and vomiting (CINV) management and outcomes: A quantitative market research-based survey. Cancer Rep (Hoboken). 2018;1(4):e1127. https://doi.org/10.1002/cnr2.1127.

The authors declare that there are no conflicts of interest present.