Radyoterapiye Bağlı Bulantı ve Kusma: Profilaksi ve Tedavi
Özet
Radyoterapiye bağlı bulantı ve kusma (RINV), klinik açıdan önemli bir yan etki olup hastaların tedavi süreçlerini aksatmalarına veya reddetmelerine yol açabilmektedir. Kusma, beyin sapında yer alan ve kemoreseptör tetikleyici bölge (CTZ) ile yakın ilişkisi bulunan kusma merkezi tarafından koordine edilen karmaşık bir reflekstir. RINV'nin insidansı ve şiddeti; ışınlanan bölge, hacim, doz ve hasta odaklı faktörlere bağlı olarak değişiklik gösterir. Kılavuzlar, emezis riskini lokalizasyona göre yüksek (tüm vücut), orta (üst abdomen, kranyospinal), düşük ve minimal olarak dört kategoriye ayırmaktadır. Profilaksi ve tedavide en etkin ajanlar 5-hidroksitriptamin (5-HT3) reseptör antagonistleri olarak öne çıkmaktadır. Ayrıca, üst batın ışınlamalarında deksametazon gibi kortikosteroidlerin eklenmesi antiemetik etkinliği artırmaktadır. Eşzamanlı kemoradyoterapi alan hastalarda ise nörokinin-1 (NK-1) reseptör antagonistleri (aprepitant, fosaprepitant) ile olanzapin kombinasyonlarının tedavide belirgin bir klinik fayda sağladığı ve bulantı-kusma riskini azalttığı gösterilmiştir. Fraksiyone radyoterapi alan hastalarda profilaksi süresi genellikle tedavi boyunca uygulanmakta olup bireysel faktörlere göre değerlendirilmektedir.
Radiotherapy-induced nausea and vomiting (RINV) is a clinically significant side effect that can cause patients to delay or refuse their treatment. Vomiting is a complex reflex coordinated by the vomiting center in the brainstem, which is closely associated with the chemoreceptor trigger zone (CTZ). The incidence and severity of RINV vary depending on factors such as the irradiated area, volume, dose, and patient-specific variables. Guidelines classify emesis risk based on localization into four categories: high (total body), moderate (upper abdomen, craniospinal), low, and minimal. The most effective agents in prophylaxis and treatment are 5-hydroxytryptamine (5-HT3) receptor antagonists. Additionally, adding corticosteroids like dexamethasone increases antiemetic efficacy in upper abdomen irradiations. In patients receiving concurrent chemoradiotherapy, combinations of neurokinin-1 (NK-1) receptor antagonists (aprepitant, fosaprepitant) and olanzapine have been shown to provide significant clinical benefit and reduce the risk of nausea and vomiting. For patients receiving fractionated radiotherapy, the duration of prophylaxis is generally applied throughout the RT period and evaluated based on individual factors.
Referanslar
Petra Feyer M, Karin Jordan M. Radiotherapy-induced nausea and vomiting: Prophylaxis and treatment 2021 [Available from: https://www.uptodate.com/contents.
Babaoğlu M.Ö, Kayaalp S.O. EMETİK, Antiemetik ve Prokinetik İlaçlar. In: Kayaalp S.O, editor. Akılcıl Tedavi Yönünden Tıbbi Farmakoloji. Ankara: Pelikan Yayıncılık; 2012. p. 1442-1454.
Maranzano E, De Angelis V, Pergolizzi S, Lupattelli M, Frata P, Spagnesi S, et al. A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres. Radiother Oncol. 2010;94(1):36-41.
Enblom A, Bergius Axelsson B, Steineck G, Hammar M, Borjeson S. One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient. Support Care Cancer. 2009;17(1):23-32.
Poon M, Hwang J, Dennis K, DeAngelis C, Zhang L, Chung H, et al. A novel prospective descriptive analysis of nausea and vomiting among patients receiving gastrointestinal radiation therapy. Support Care Cancer. 2016;24(4):1545-61.
Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011;29(31):4189-98.
Ruhlmann CH, Jahn F, Jordan K, Dennis K, Maranzano E, Molassiotis A, et al. 2016 updated MASCC/ESMO consensus recommendations: prevention of radiotherapy-induced nausea and vomiting. Support Care Cancer. 2017;25(1):309-16.
Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, 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-v33.
Kirkbride P, Bezjak A, Pater J, Zee B, Palmer MJ, Wong R, et al. Dexamethasone for the prophylaxis of radiation-induced emesis: a National Cancer Institute of Canada Clinical Trials Group phase III study. J Clin Oncol. 2000;18(9):1960-6.
Chow E, Meyer RM, Ding K, Nabid A, Chabot P, Wong P, et al. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(15):1463-72.
National Cancer Institute of Canada Clinical Trials G, Wong RK, Paul N, Ding K, Whitehead M, Brundage M, et al. 5-hydroxytryptamine-3 receptor antagonist with or without short-course dexamethasone in the prophylaxis of radiation induced emesis: a placebo-controlled randomized trial of the National Cancer Institute of Canada Clinical Trials Group (SC19). J Clin Oncol. 2006;24(21):3458-64.
Yamamoto K, Nohara K, Furuya T, Yamatodani A. Ondansetron, dexamethasone and an NK1 antagonist block radiation sickness in mice. Pharmacol Biochem Behav. 2005;82(1):24-9.
Jahn F, Riesner A, Jahn P, Sieker F, Vordermark D, Jordan K. Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin. Int J Radiat Oncol Biol Phys. 2015;92(5):1101-7.
Ruhlmann CH, Christensen TB, Dohn LH, Paludan M, Ronnengart E, Halekoh U, et al. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol. 2016;17(4):509-18.
Roila F, Ciccarese G, Palladino MA, De Angelis V. Prevention of radiotherapy-induced emesis. Tumori. 1998;84(2):274-8.
Navari RM, Nagy CK, Le-Rademacher J, Loprinzi CL. Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting. J Community Support Oncol. 2016;14(4):141-7.
Dennis K, Zhang L, Lutz S, van Baardwijk A, van der Linden Y, Holt T, et al. International patterns of practice in the management of radiation therapy-induced nausea and vomiting. Int J Radiat Oncol Biol Phys. 2012;84(1):e49-60.
