Zusammenfassung
Die simultane Radiochemotherapie (RCT) ist der Behandlungsstandard bei lokal fortgeschrittenen nichtkleinzelligen Bronchialkarzinomen (NSCLC) im Stadium III und in limitierten Stadien des kleinzelligen Bronchialkarzinoms bei Inoperabilität. Die Nebenwirkungen sind abhängig von den eingesetzten Substanzen, den strahlentherapeutischen Parametern und den Patientencharakteristika. Im Beitrag wird der Umgang mit häufigen und relevanten Nebenwirkungen einer RCT des Bronchialkarzinoms zusammengefasst und diskutiert. Die Chemotherapie enthält meist ein stark emetogenes Platinderivat. Daher ist die Prophylaxe von chemotherapieassoziierter Übelkeit und Erbrechen mit 5‑HT3- („Serotonin 5-hydroxytryptamin 3“) und NK-1(Neurokinin-1)-Rezeptorantagonisten sowie Dexamethason ein essenzieller Baustein des peritherapeutischen Managements. Die ebenfalls primär chemotherapiebedingte Hämatotoxizität wird je nach Schweregrad und betroffener Blutzellreihe mit Wachstumsfaktoren und Bluttransfusionen therapiert. Im Gegensatz dazu können die radiogen verursachten Veränderungen besonders im Bereich Speiseröhre und Lunge meist nicht kausal, sondern nur symptomatisch therapiert werden. Die Prophylaxe und Behandlung des weiten Spektrums an Nebenwirkungen einer Radiochemotherapie beim Bronchialkarzinom sollte unter sorgfältiger Abwägung des Schweregrades, des Behandlungserfolges und der damit assoziierten Risiken erfolgen.
Abstract
Simultaneous chemoradiotherapy (CRT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC) in stage III and for limited stages of small cell lung cancer (SCLC) and nonoperability. The side effects depend on the cytotoxic agents employed, the radiotherapeutic parameters and the patient characteristics. This article summarizes and discusses the management strategies for frequent and relevant side effects of CRT of lung cancer. The chemotherapy mostly includes a highly emetogenic platinum derivative. Therefore, prophylaxis of chemotherapy-associated nausea and vomiting with serotonin 5‑hydroxytryptamine‑3 (5-HT3) and neurokinin 1 (NK1) receptor antagonists and dexamethasone is an essential element of peritherapeutic management. The management of likewise primary chemotherapy-induced hematologic side effects depends on the severity and the affected blood cell lineage and involves growth factors and blood transfusions. In contrast, radiotherapy-induced alterations, especially of the lungs and esophagus can mostly not be causally treated but are treated symptomatically. The prophylaxis and treatment of the broad spectrum of side effects of CRT of lung cancer should be based on a thorough evaluation of the severity of symptoms, the treatment efficacy and associated risks.
Literatur
Aapro M et al (2018) Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines. Ann Oncol 29(Suppl 4):iv96–iv110. https://doi.org/10.1093/annonc/mdx758
Alderman B et al (2022) Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer. Support Care Cancer 31(1):39. https://doi.org/10.1007/s00520-022-07480-x
Antonadou D et al (2003) Amifostine reduces radiochemotherapy-induced toxicities in patients with locally advanced non-small cell lung cancer. Semin Oncol 30(6 Suppl 18):2–9. https://doi.org/10.1053/j.seminoncol.2003.11.008
Antonadou D et al (2003) Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 57(2):402–408. https://doi.org/10.1016/s0360-3016(03)00590-x
Antonadou D et al (2001) Randomized phase III trial of radiation treatment +/− amifostine in patients with advanced-stage lung cancer. Int J Radiat Oncol Biol Phys 51(4):915–922. https://doi.org/10.1016/s0360-3016(01)01713-8
Ardizzoni A et al (2007) Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst 99(11):847–857. https://doi.org/10.1093/jnci/djk196
Auerbach M et al (2010) Darbepoetin alfa 300 or 500 μg once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. Am J Hematol 85(9):655–663. https://doi.org/10.1002/ajh.21779
Auerbach M et al (2004) Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J Clin Oncol 22(7):1301–1307. https://doi.org/10.1200/JCO.2004.08.119
Aupérin A et al (2010) Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 28(13):2181–2190. https://doi.org/10.1200/JCO.2009.26.2543
AWMF: Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Supportive Therapie bei onkologischen PatientInnen – Langversion 1.3, 2020, AWMF Registernummer: 032/054OL, https://www.leitlinienprogramm-onkologie.de/leitlinien/supportive-therapie/ Zugriff am 12. Aug. 2023.
Bi N et al (2020) Efficacy and safety of concurrent chemoradiotherapy in ECOG 2 patients with locally advanced non-small-cell lung cancer: a subgroup analysis of a randomized phase III trial. BMC Cancer 20(1):278. https://doi.org/10.1186/s12885-020-06780-x
Bundesärztekammer Querschnitts-Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten. https://www.bundesaerztekammer.de/fileadmin/user_upload/_old-files/downloads/pdf-Ordner/MuE/Querschnitts-Leitlinien_BAEK_zur_Therapie_mit_Blutkomponenten_und_Plasmaderivaten-Gesamtnovelle_2020.pdf. Zugegriffen: 25. März 2023
Bunn PA et al (1995) Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 13(7):1632–1641. https://doi.org/10.1200/JCO.1995.13.7.1632
Challand T et al (2012) Esophageal toxicity of radiation therapy: clinical risk factors and management. Cancer Radiother 16(5–6):364–371. https://doi.org/10.1016/j.canrad.2012.07.180
Chen Y et al (2018) Comparing the benefits of chemoradiotherapy and chemotherapy for resectable stage III A/N2 non-small cell lung cancer: a meta-analysis. World J Surg Onc 16(1):1–10. https://doi.org/10.1186/s12957-018-1313-x
Cutler A et al (2010) Rabeprazole 20 mg for erosive esophagitis-associated symptoms in a large, community-based study: additional results. Dig Dis Sci 55(2):338–345. https://doi.org/10.1007/s10620-009-0864-7
Osoba D (1997) Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group. JCO 15:1. https://doi.org/10.1200/JCO.1997.15.1.116
Duran M et al (2010) Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 70(5):656–663. https://doi.org/10.1111/j.1365-2125.2010.03743.x
Fonte C et al (2015) A review of olanzapine as an antiemetic in chemotherapy-induced nausea and vomiting and in palliative care patients. Crit Rev Oncol Hematol 95(2):214–221. https://doi.org/10.1016/j.critrevonc.2015.02.010
Franzén L et al (1996) A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 7(6):587–592. https://doi.org/10.1093/oxfordjournals.annonc.a010675
Ganzoni AM (1970) Intravenous iron-dextran: therapeutic and experimental possibilities. Schweiz Med Wochenschr 100(7):301–303
Glaspy J, Dunst J (2004) Can erythropoietin therapy improve survival? Oncology 67(Suppl 1):5–11. https://doi.org/10.1159/000080705
Gomes F et al (2021) Safety of G‑CSF with concurrent chemo-radiotherapy in limited-stage small cell lung cancer—Secondary analysis of the randomised phase 3 CONVERT trial. Lung Cancer 153:165–170. https://doi.org/10.1016/j.lungcan.2021.01.025
Griffiths EA et al (2022) NCCN Guidelines® Insights: Hematopoietic Growth Factors, Version 1.2022. J Natl Compr Canc Netw 20(5):436–442. https://doi.org/10.6004/jnccn.2022.0026
Henry DH et al (2007) Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist 12(2):231–242. https://doi.org/10.1634/theoncologist.12-2-231
Hesketh PJ et al (2014) 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 25(7):1340–1346. https://doi.org/10.1093/annonc/mdu110
Hicks LK et al (2013) The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. Hematology Am Soc Hematol Educ Program 2013:9–14. https://doi.org/10.1182/asheducation-2013.1.9
Jahn F et al (2022) The prevention and treatment of nausea and vomiting during tumor therapy. Dtsch Ärztebl Int 119(21):382–392. https://doi.org/10.3238/arztebl.m2022.0093
Jordan K et al Onkopedia Leitlinie Antiemese bei medikamentöser Tumortherapie. https://www.onkopedia.com/de/onkopedia/guidelines/antiemese-bei-medikamentoeser-tumortherapie/@@guideline/html/index.html. Zugegriffen: 3. Aug. 2023
Klastersky J et al (2016) Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol 27:v111–v118. https://doi.org/10.1093/annonc/mdw325
Komaki R et al (2004) Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial. Int J Radiat Oncol Biol Phys 58(5):1369–1377. https://doi.org/10.1016/j.ijrobp.2003.10.005
Koning CC et al (2013) Toxicity of concurrent radiochemotherapy for locally advanced non–small-cell lung cancer: a systematic review of the literature. Clin Lung Cancer 14(5):481–487. https://doi.org/10.1016/j.cllc.2013.03.002
Kosmidis P et al (2005) Anemia profiles in patients with lung cancer: what have we learned from the European Cancer Anaemia Survey (ECAS)? Lung Cancer 50(3):401–412. https://doi.org/10.1016/j.lungcan.2005.08.004
Liang J et al (2017) Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol 28(4):777–783. https://doi.org/10.1093/annonc/mdx009
Link H (2022) Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF). Support Care Cancer 30(9):7067–7077. https://doi.org/10.1007/s00520-022-07103-5
Link H (2022) G‑CSF zur Prophylaxe der Neutropenie und der febrilen Neutropenie, Anämie bei Krebserkrankung. Best Practice Onkologie 17(6):298–314. https://doi.org/10.1007/s11654-022-00398-0
Lokich J, Anderson N (1998) Carboplatin versus cisplatin in solid tumors: an analysis of the literature. Ann Oncol 9(1):13–21. https://doi.org/10.1023/a:1008215213739
Ludwig H et al (2004) The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer 40(15):2293–2306. https://doi.org/10.1016/j.ejca.2004.06.019
Maranzano E et al (2010) A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres. Radiother Oncol 94(1):36–41. https://doi.org/10.1016/j.radonc.2009.11.001
McCarty MJ et al (1996) Azathioprine as a steroid-sparing agent in radiation pneumonitis. Chest 109(5):1397–1400. https://doi.org/10.1378/chest.109.5.1397
Muraoka T et al (2002) Corticosteroid refractory radiation pneumonitis that remarkably responded to cyclosporin A. Intern Med 41(9):730–733. https://doi.org/10.2169/internalmedicine.41.730
National Cancer Institute of Canada Clinical Trials Group (SC19) et al (2006) 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 24(21):3458–3464. https://doi.org/10.1200/JCO.2005.04.4685
Onishi H et al (2003) Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: a good local response but no good survival due to radiation pneumonitis. Cancer Treat Res 40(1):79–84. https://doi.org/10.1016/s0169-5002(02)00532-9
O’Rourke N et al (2010) Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD002140.pub3
Palma DA et al (2013) Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 85(2):444–450. https://doi.org/10.1016/j.ijrobp.2012.04.043
Parashar B et al (2011) Chemotherapy significantly increases the risk of radiation pneumonitis in radiation therapy of advanced lung cancer. Am J Clin Oncol 34(2):160–164. https://doi.org/10.1097/COC.0b013e3181d6b40f
Peterson DE et al (2011) Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol 22(Suppl 6):vi78–vi84. https://doi.org/10.1093/annonc/mdr391
Rodrigues G et al (2004) Prediction of radiation pneumonitis by dose-volume histogram parameters in lung cancer—a systematic review. Radiother Oncol 71(2):127–138. https://doi.org/10.1016/j.radonc.2004.02.015
Roila F et al (2016) 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. https://doi.org/10.1093/annonc/mdw270
Roila F et al (2017) 2016 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high emetic risk chemotherapy. Support Care Cancer 25(1):277–288. https://doi.org/10.1007/s00520-016-3313-0
Roila F et al (2017) 2016 updated MASCC/ESMO consensus recommendations: Prevention of nausea and vomiting following moderately emetogenic chemotherapy. Support Care Cancer 25(1):289–294. https://doi.org/10.1007/s00520-016-3365-1
Sheikh H et al (2011) Use of G‑CSF during concurrent chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer safety data from a phase II trial. Lung Cancer 74(1):75–79. https://doi.org/10.1016/j.lungcan.2011.01.020
Singh AK et al (2003) Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 55(2):337–341. https://doi.org/10.1016/s0360-3016(02)03937-8
Smith TJ et al (2015) Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 33(28):3199–3212. https://doi.org/10.1200/JCO.2015.62.3488
Steensma DP et al (2011) Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to Darbepoetin alfa for patients with chemotherapy-associated anemia. J Clin Oncol 29(1):97–105. https://doi.org/10.1200/JCO.2010.30.3644
Tj S et al (2015) Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 33:28. https://doi.org/10.1200/JCO.2015.62.3488
Werner-Wasik M et al (2011) Acute esophagitis and late lung toxicity in concurrent chemoradiotherapy trials in patients with locally advanced non-small-cell lung cancer: analysis of the radiation therapy oncology group (RTOG) database. Clin Lung Cancer 12(4):245–251. https://doi.org/10.1016/j.cllc.2011.03.026
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Interessenkonflikt
K.M. Kraus, R. Eichner und S.E. Combs geben an, dass kein Interessenkonflikt besteht.
Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.
Additional information
Redaktion
Petra Feyer, Berlin
Hinweis des Verlags
Der Verlag bleibt in Hinblick auf geografische Zuordnungen und Gebietsbezeichnungen in veröffentlichten Karten und Institutsadressen neutral.
Rights and permissions
About this article
Cite this article
Kraus, K.M., Eichner, R. & Combs, S.E. Kombination Radio(chemo)therapie beim Lungenkarzinom – Nebenwirkungsmanagement. best practice onkologie 18, 496–507 (2023). https://doi.org/10.1007/s11654-023-00529-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11654-023-00529-1