Возможности профилактики тошноты при цитостатической терапии: обзор литературы и клиническое наблюдение

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.

1. 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.

2. 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.

3. 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/.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. Siddiqui M.A., Scott L.J. Palonosetron. Drugs. 2004;64(10):1125–1132. https://doi.org/10.2165/00003495-200464100-00006.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.