nach oben

Drugs & Aging

Erschienen in:

09.12.2021 | Therapy in Practice

Prevention of Chemotherapy-Induced Nausea and Vomiting in the Older Patient: Optimizing Outcomes

verfasst von: Jørn Herrstedt, Sanne Lindberg, Peter Clausager Petersen

Erschienen in: Drugs & Aging | Ausgabe 1/2022

Einloggen, um Zugang zu erhalten

Abstract

Chemotherapy-induced nausea and vomiting (CINV) are still two of the most feared side effects of cancer therapy. Although major progress in the prophylaxis of CINV has been made during the past 40 years, nausea in particular remains a significant problem. Older patients have a lower risk of CINV than younger patients, but are at a higher risk of severe consequences of dehydration and electrolyte disturbances following emesis. Age-related organ deficiencies, comorbidities, polypharmacy, risk of drug–drug interactions, and lack of compliance all need to be addressed in the older patient with cancer at risk of CINV. Guidelines provide evidence-based recommendations for the prophylaxis of CINV, but none of these guidelines offer specific recommendations for older patients with cancer. This means that the recommendations may lead to overtreatment in some older patients. This review describes the development of antiemetic prophylaxis of CINV focusing on older patients, summarizes recommendations from antiemetic guidelines, describes deficiencies in our knowledge of older patients, summarizes necessary precautions, and suggests some future perspectives for antiemetic research in older patients.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.PubMed

Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. Global cancer observatory: cancer today. Lyon, France: International Agency for Research on Cancer. 2020. https://gco.iarc.fr/today. Accessed 01 July 2021.

Arnold M, Rutherford MJ, Bardot A, Ferlay J, Andersson TML, Myklebust TA, et al. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol. 2019;20:1493–505.PubMedPubMedCentral

Jørgensen TL, Hallas J, Land LH, Herrstedt J. Comorbidity and polypharmacy in elderly cancer patients: the significance on treatment outcome and tolerance. J Geriatr Oncol. 2010;1:87–102.

Herrstedt J. The latest consensus on antiemetics. Curr Opin Oncol. 2018;30:233–9.PubMed

Dranitsaris G, Molassiotis A, Clemons M, et al. The development of a prediction tool to identify cancer patients in high risk of chemotherapy-induced nausea and vomiting. Ann Oncol. 2018;28:1260–7.

Jordan K, Chan A, Gralla RJ, Jahn F, Rapoport B, Warr D, et al. 2016 updated MASCC/ESMO consensus recommendations: emetic risk classification and evaluation of the emetogenicity of antineoplastic agents. Support Care Cancer. 2017;25:271–5.PubMed

Ajeet G, Klepin HD, Feng T, Tew WP, Mohile SG, Owusu C, et al. Predictors of chemotherapy dose reduction at first cycle in patients aged 65 years and older with solid tumors. J Geriatr Oncol. 2015;6:133–40.

Mizuno M, Hiura M, Kikkawa F, Numa F, Yaegashi N, Narahara H, et al. A prospective observational study on chemotherapy-induced nausea and vomiting (CINV) in patients with gynaecologic cancer by the CINV Study Group of Japan. Gynecol Oncol. 2016;140:559–64.PubMed

10.

Hesketh PJ, Aapro M, Street JC, 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. 2010;18:1171–7.PubMed

11.

Daiki T, Suzuki K, Kawasaki Y, Goto K, Matsui R, Seki N, et al. Risk factors associated with chemotherapy-induced nausea and vomiting in the triplet antiemetic regimen including palonosetron or granisetron for cisplatin-based chemotherapy: analysis of a randomized, double-blind controlled trial. Support Care Cancer. 2019;27:1139–47.

12.

Rha SY, Park Y, Song SK, Lee CE, Lee J. Controlling chemotherapy-induced nausea requires further improvement: symptom experience and risk factors among Korean patients. Support Care Cancer. 2016;24:3379–89.PubMed

13.

Hayashi T, Shimokawa M, Matsuo K, Miyoshi T, Toriyama Y, Yokota C. Risk factors for delayed chemotherapy-induced nausea and vomiting with low-emetic-risk chemotherapy: a prospective, observational, multicenter study. Cancer Manag Res. 2018;10:4249–55.PubMedPubMedCentral

14.

Furukawa N, Akasaka J, Shigemitsu A, Sasaki Y, Nagai A, Kawaguchi R, et al. 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;289:859–64.PubMed

15.

Tsuji Y, Baba H, Takeda K, Kobayashi M, Oki E, Gotoh M, et al. Chemotherapy-induced nausea and vomiting (CINV) in 190 colorectal cancer patients: a prospective registration study by the CINV study group of Japan. Expert Opin Pharmacother. 2017;18:753–8.PubMed

16.

Aapro M, Molassiotis A, Dicato M, Peláez I, Rodríguez-Lescure Á, Pastorelli D, et al. The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol. 2012;23:1986–92.PubMed

17.

ESMO Handbook of Cancer in the Senior Patient. In: Matti SA, Dirk S. editors. 2nd ed. 2015.

18.

Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology Consensus on geriatric asessment in older people with cancer. J Clin Oncol. 2014;32:2595–603.PubMedPubMedCentral

19.

Soenen S, Rayner CK, Jones KL, Horowitz M. The ageing gastrointestinal tract. Curr Opin Nutr Metab Care. 2016;19:12–8.

20.

Tveito M, Smith RL, Molden E, et al. Age impacts olanzapine exposure differently during use of oral versus long-acting injectable formulations: an observational study including 8,288 patients. J Clin Psychopharmacol. 2018;38:570–6.PubMed

21.

Weinstein JR, Anderson S. The aging kidney: physiological changes. Adv Chronic Kidney Dis. 2010;17:302–7.PubMedPubMedCentral

22.

Eriksen BO, Stefansson VTN, Jenssen TG, Mathisen UD, Schei J, Solbu MD, et al. Elevated blood pressure is not associated with accelerated glomerular filtration rate decline in the general non-diabetic middle-aged population. Kidney Int. 2016;90:404–10.PubMed

23.

Peterson LL, Hurria A, Feng T, et al. Association betweeen renal function and chemotherapy-related toxicity in older adults with cancer. J Geriatr Oncol. 2017;8:96–1010.PubMed

24.

Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin. 2012;8:143–64.PubMedPubMedCentral

25.

Brygger L, Herrstedt J. 5-Hydroxytryptamine₃ receptor antagonists and cardiac side effects. Expert Opin Drug Saf. 2014;13:1407–22.PubMed

26.

Hartsock RJ, Smith EB, Petty CS. Normal variants with aging of the amount of hematopoietic tissue in bone marrow from the anterior iliac crest. A study made from 177 cases of sudden death examined by necropsy. Am J Clin Pathol. 1965;43:326–31.PubMed

27.

Lyman GH, Abella E, Pettengell R. Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: a systematic review. Crit Rev Oncol Hematol. 2014;90:190–9.PubMed

28.

Guida JL, Agurs-Collins T, Ahles TA, Campisi J, Dale W, Demark-Wahnefried W, et al. Stategies to prevent or remediate cancer and treatment-related aging. J Natl Cancer Inst. 2021;113:112–22.PubMed

29.

Chudiak A, Uchmanowicz I, Mazur G. Relation between cognitive impairment and treatment adherence in elderly hypertensive patients. Clin Intervent Aging. 2018;13:1409–18.

30.

Ofori-Asenso R, Chin KL, Curtis AJ, Zomer E, Zoungas S, Liew D. Recent patterns of multimorbidity among older adults in high-income countries. Popul Health Manag. 2019;22:127–37.PubMed

31.

Jørgensen TL, Hallas J, Friis S, Herrstedt J. Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality. Br J Cancer. 2012;106:1353–60.PubMedPubMedCentral

32.

Koo MM, Swann R, McPhail S, Abel GA, Renzi C, Rubin GP, et al. The prevalence of chronic conditions in patients diagnosed with one of 29 common and rarer cancers: a cross-sectional study using primary care data. Cancer Epidemiol 2020;69:101845. https://doi.org/10.1016/j.canep.2020.101845.CrossRefPubMedPubMedCentral

33.

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.PubMed

34.

Linn BS, Lin MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16:622–6.PubMed

35.

Masnoon N, Shakib S, Ellett LK, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17:230.PubMedPubMedCentral

36.

Corbett T, Bridges J. Multimorbidity in older adults living with and beyond cancer. Curr Opin Support Palliat Care. 2019;13:220–4.PubMed

37.

Korc-Grodzicki B, Boparai MK, Lichtman SM. Prescribing for older patients with cancer. Clin Adv Hematol Oncol. 2014;12:309–18.PubMed

38.

Jørgensen TL, Herrstedt J, Friis S, Hallas J. Polypharmacy and drug use in elderly Danish cancer patients during 1996–2006. J Geriatr Oncol. 2012;3:33–40.

39.

Beinse G, Reitter D, Segaux L, Carvahlo-Verlinde M, Rousseau B, Tournigand C, et al. Potential drug–drug interactions and risk of umplanned hospitalization in older patients with cancer: a survey of the prospective ELCAPA (ELderly CAncer PAtients) cohort. J Geriatr Oncol. 2020;11:586–92.PubMed

40.

Carlsson A, Lindqvist M, Magnusson T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophane as reserpine antagonists. Nature. 1957;180:1200.PubMed

41.

Shen WW, Baig MS, Sata LS, Hofstatter L. Dopamine receptor supersensitivity and the chemoreceptor trigger zone. Biol Psychiatry. 1983;18:917–21.PubMed

42.

Yoshida N, Yoshikawa T, Hosoki K. A dopamine D3 receptor agonist, 7-OH-DPAT, causes vomiting in the dog. Life Sci. 1995;57:347–50.

43.

Herrstedt J, Summers Y, Jordan K, Von Pawel J, Jakobsen AH, Ewertz M, Chan S, Naik JD, Karthaus M, Dubey S, Davis R, Fox GM. Amisulpride prevents nausea and vomiting associated with highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled, dose-ranging trial. Support Care Cancer. 2019;27:2699–705.PubMed

44.

Moertel C, Reitemeier RJ. Controlled clinical studies of orally administered antiemetic drugs. Gastroenterology. 1969;57:262–8.PubMed

45.

Moertel C, Reitemeier RJ. Controlled studies of metopimazine for the treatment of nausea and vomiting. J Clin Pharmacol. 1973;13:283–7.PubMed

46.

Herrstedt J, Sigsgaard T, Boesgaard M, Jensen TP, Dombernowsky P. Ondansetron plus metopimazine compared with ondansetron alone in patients receiving moderately emetogenic chemotherapy. N Engl J Med. 1993;328:1076–80.PubMed

47.

Herrstedt J, Sigsgaard T, Handberg J, Schousboe BMB, Hansen M, Dombernowsky P. Randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with cancer. J Clin Oncol. 1997;15:1690–6.PubMed

48.

Jolliet P, Nion S, Allain-Veyrac G, Tilloy-Fenart L, Vanuxeem D, Berezowsky V, Cecchelli R. Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood-brain barrier. Pharmacol Res. 2007;56:11–7.PubMed

49.

Frytak S, Moertel CG, Eagan RT, O’Fallon JR. A double-blind comparison of metoclopramide and prochlorpearzine as antiemetics for platinum therapy. Proc Am Soc Clin Oncol. 1981;22:421.

50.

Olver IN, Wolf M, Laidlaw C, Bishop JF, Cooper IA, Matthews J, Smith R, Buchanan L. A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer chemotherapy. Eur J Cancer. 1992;28A:1798–802.PubMed

51.

Sallan SE, Cronin C, Zelen M, Zinberg NE. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med. 1980;302:135–8.PubMed

52.

Roscoe JA, Heckler CE, Morrow GR, Mohile SG, Dakhil SR, Wade JL, Kuebler JP. Prevention of delayed nausea: A University Rochester Cancer Center Community Clinical Oncology Program Study of patients receiving chemotherapy. J Clin Oncol. 2012;30:3389–95.PubMedPubMedCentral

53.

Justin-Besancon L, Laville C. Action antiémétique du métoclopramide vis-à-vis de l’apomorphine et de l’hydergine. CR Soc Biol (Paris). 1964;158:723.

54.

Pinder RM, Brogden RN, Sawyer R, Speight TM, Avery GS. Metoclopramide: a review of its pharmacological properties and clinical use. Drugs. 1976;12:81–131.PubMed

55.

Cunningham D, Evans C, Gazet JC, Ford H, People A, Dearling J, Chappell D, Coombes C. Comparison of antiemetic efficacy of domperidone, metoclopramide, and dexamethasone in patients receiving outpatient chemotherapy regimens. BMJ. 1987;295(6592):250.PubMedPubMedCentral

56.

Gralla RJ, Itri L, Pisko SE, Squillante AE, Kelsen DP, Braun DW, Bordin LA, Braun TJ, Young CW. Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J med. 1981;305:905–9.PubMed

57.

Warrington PS, Allan SG, Cornbleet MA, MacPherson JS, Smyth JF, Leonard RCF. Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high dose metoclopramide in emesis induced by cisplatin. BMJ. 1986;293:1334–7.PubMedPubMedCentral

58.

Kris MG, Gralla RJ, Clark RA, Tyson LB, Groshen S. Antiemetic control and prevention of side effects of antiemetic cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide and dexamethasone. Cancer. 1987;60:2816–22.PubMed

59.

Roila F, Tonato M, Basurto C, Picciafuoco M, Bracarda S, Donati D, Malacarne P, Monici L, Di Costanzo F, Patoia L, Ballatori E, Tognoni G, Del Favero A. Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methylprednisolone versus metoclopramide combined with dexamethasone and diphenhydramine: a study of the Italian Oncology Group for Clinical Research. J Clin Oncol. 1989;7:1693–700.PubMed

60.

Fozard JR, Mobarok ALIA. Blockade of neuronal tryptamine receptors by metoclopramide. Eur J Pharmacol. 1978;49:109–12.PubMed

61.

Fozard JR. MDL 72222, a potent and highly antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1984;326:36–44.PubMed

62.

Miner WD, Sanger GJ. Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M receptor antagonism. Br J Pharmacol. 1986;88:497–9.PubMedPubMedCentral

63.

Costall B, Domeney AM, Naylor RJ, Tattersall FD. 5-hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. Neuropharmacol. 1986;25:959–61.

64.

Joss RA, Goldhirsch A, Brunner KW, Galeazzi RL. Sudden death in cancer patients after high-dose domperidone. Lancer. 1982;1:1019.

65.

Roussak JB, Carey P, Parry H. Cardiac arrest after treatment with intravenous domperidone. BMJ. 1984;8:1579.

66.

Giaccone G, Bertetto O, Calciati A. Two sudden deaths during prophylactic antiemetic treatment with high doses of domperidone and methylprednisolone. Lancet. 1984;8:1336.

67.

Osborne RJ, Slevin ML, Hunter RW, Hamer J. Cardiotoxicity of intravenous domperidone. Lancet. 1985;17:385.

68.

Huys J. Cytostatic-associated vomiting effectively inhibited by domperidone (R 33812). Cancer Chenother Pharmacol. 1978;1:215–8.

69.

Roila F, Tonato M, Basurto C, Minotti V, Ballatori E, Del Favero A. Double-blind controlled trial of the antiemetic efficacy and toxicity of methylprednisolone (MP), metoclopramide (MTC) and domperidone (DMP) in breast cancer patients treated with i.v. CMF. Eur J Cancer Clin Oncol. 1987;23:615–7.PubMed

70.

Baker JJ, Lokey JL, Price NA, Winokur SH, Bowen J. Nabilone as an antiemetic (use of high dose dexamethasone). N Engl J Med. 1979;301:728.PubMed

71.

Markman M, Sheidler V, Ettinger DS, Quaskey SA, Mellits ED. Antiemetic efficacy of dexamethasone. Randomized, double-blind, crossover study with prochlorperazine in patients receiving cancer chemotherapy. N Engl J Med. 1984;311:549–52.PubMed

72.

Roila F, Tonato M, Cognetti F, Cortesi F, Favalli G, Marangolo M, Amadori D, Bella MA, Gramazio V, Donati D, Ballatori E, Del Favero A. Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. J Clin Oncol. 1991;9:675–8.PubMed

73.

The Italian Group for Antiemetic Research. Dexamethasone, granisetron or both for the prevention of nausea and vomiting during chemotherapy for cancer. N Engl J Med. 1995;332:1–5.

74.

Leibundgut U, Lancranjan I. First results with ICS 205–930 (5-HT3 receptor antagonis) in prevention of chemotherapy-induced emesis. Lancet. 1987;1(8543):1198.PubMed

75.

Cunningham D, Hawthorn J, Pople A, Gazet J-C, Ford HT, Challoner T, Coombes RC. Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Lancet. 1987;1(8548):1461–3.PubMed

76.

Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med. 1990;322:810–6.PubMed

77.

Cubeddu LX, Hoffman IS, Fuenmayor NT, Finn AL. Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens. J Clin Oncol. 1990;8:1721–7.PubMed

78.

Marty M, Pouillart P, Scholl S, Droz JP, Azab M, Brion N, Pujade-Lauraine E, Paule B, Paes D, Bons J. Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. N Engl J Med. 1990;322:816–21.PubMed

79.

Bonneterre J, Chevallier B, Metz R, Fargeot P, Pujade-Lauraine E, Spielmann M, Tubiana-Hulin M, Paes D, Bons J. A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy. J Clin Oncol. 1990;8:1063–9.PubMed

80.

Kaasa S, Kvaløy S, Dicato MA, Ries F, Huys JV, Royer E, Carruthers L, International Emesis Study Group. A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. International Emesis Study Group. Eur J Cancer. 1990;26:311–4.PubMed

81.

Marschner NW, Adler M, Nagel GA, Christmann D, Fenzl E, Upadhyaya B. Double-blind randomised trial of the antiemetic efficacy and safety of ondansetron and metoclopramide in advanced breast cancer patients treated with epirubicin and cyclophosphamide. Eur J Cancer. 1991;27:1137–40.PubMed

82.

Jones AL, Hill AS, Soukop M, Hutcheon AW, Cassidy J, Kaye SB, Sikora K, Carney DN, Cunningham D. Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy. Lancet. 1991;24(338):483–7.

83.

Warr D, Willan A, Fine S, Wilson K, Davis A, Erlichman C, Rusthoven J, Lofters W, Osoba D, Laberge F, Latreille J, Pater J. Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis. J Natl Cancer Inst. 1991;83:1169–73.PubMed

84.

Warr D, Wilan A, Venner P, Pater J, Kaizer L, Laberge F, Latreille J, Stewart D, O’Connell G, Osoba D, Wilson K, Davis A, Johnston D. A randomised, double-blind comparison of granisetron with high-dose metoclopramide, dexamethasone and diphenhydramine for cisplatin-induced emesis. An NCI Canada Clinical Trials Group Phase III Trial. Eur J Cancer. 1992;29A:33–6.PubMed

85.

Perez EA, Hesketh P, Sandbach J, Reeves J, Chawla S, Markman M, Hainsworth J, Bushnell W, Friedman C. Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. J Clin Oncol. 1998;16:754–60.PubMed

86.

Gralla RJ, Navari RM, Hesketh PJ, Popovic W, Strupp J, Noy J, Einhorn L, Ettinger D, Bushnell W, Friedman C. Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy. J Clin Oncol. 1998;16:1568–73.PubMed

87.

Raftopoulos H, Cooper W, O’Boyle E, Gabrail N, Boccia R, Gralla RJ. Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority, phase 3 trial. Support Care Cancer. 2015;23:723–32.PubMed

88.

Gralla R, Lichinitser M, Van der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570–7.PubMed

89.

Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT₃ receptor antagonist. Cancer. 2003;98:2473–82.PubMed

90.

Aapro MS, Grunberg SM, Manikhas GM, Olivares G, Suarez T, Tjulandin SA, Bertoli LF, Yunus F, Morrica B, Lordick F, Macciocchi A. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol. 2006;17:1441–9.PubMed

91.

Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H, Inoue K, Kitagawa C, Ogura T. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 2009;10:115–24.PubMed

92.

Morganroth J, Flaharty KK, Parisi S, Moresino C. Effect of single doses of IV palonosetron, up to 2.25 mg, on the QTC interval duration: a double-blind, randomized, parallel group study in healthy volunteers. Support Care Cancer. 2016;24:621–7.PubMed

93.

Min JJ, Yoo Y, Kim TK, Lee J-M. Intravenous palonosetron increases the incidence of QT_C prolongation during sevoflurane general anesthesia for laparotomy. Korean J Anesthesiol. 2013;65:397–402.PubMedPubMedCentral

94.

Prasad M, Shashidar VK, Chakraborty A. Palonosetron-induced ventricular tachycardia in a patient receiving cancer chemotherapy. Cureus. 2017;9: e1480. https://doi.org/10.7759/cureus.1480.CrossRef

95.

Kaiser R, Sezer O, Papies A, Bauer S, Schelenz C, Tremblay P-B, Possinger K, Roots I, Brockmöller J. Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol. 2002;20:2805–11.PubMed

96.

Kris MG, Radford JE, Pizzo BA, Inabinet R, Hesketh A, Hesketh PJ. Use of an NK1 receptor antagonist to prevent delayed emesis after cisplatin. J Natl Cancer Inst. 1997;89:817–8.PubMed

97.

Navari RM, Reinhardt RR, Gralla RJ, Kris MG, Hesketh PJ, Khojasteh A, Kindler H, Grote TH, Pendergrass K, Grunberg SM, Carides AD, Gertz B, for The L-754,030 Antiemetic Trials Group. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group. N Engl J Med. 1999;340:190–5.PubMed

98.

Campos D, Pereira JR, Reinhardt RR, Carracedo C, Poli S, Vogel C, Martinez-Cedillo J, Erazo A, Wittreich J, Eriksson L-O, Carides AD, Gertz BJ. Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol. 2001;19:1759–67.PubMed

99.

Cocquyt V, Van Belle S, Reinhardt RR, Decramer MLA, O’Brien M, Schellens JHM, Borms M, Verbeke L, Van Aelst F, De Smet M, Carides AD, Eldridge K, Gertz BJ. Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis. Eur J Cancer. 2001;37:835–42.PubMed

100.

Van Belle S, Lichinitser MR, Navari RM, Garin AM, Decramer MLA, Riviere A, Thant M, Brestan E, Bui B, Eldridge K, De Smet M, Michiels N, Reinhardt RR, Carides AD, Evans JK, Gertz BJ. Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. Cancer. 2002;94:3032–41.PubMed

101.

Chawla SP, Grunberg SM, Gralla RJ, Hesketh PJ, Rittenberg C, Elmer ME, Schmidt C, Taylor A, Carides AD, Evans JK, Horgan KJ. Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer. 2003;97:2290–300.PubMed

102.

Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, De Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin-the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003;21:4112–9.PubMed

103.

Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Ma GJ, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F, on behalf of the Aprepitant Protocol 054 Study Group. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003;97:3090–8.PubMed

104.

Schmoll HJ, Aapro MS, Poli-Bigelli S, Kim H-H, Park K, Jordan K, Von Pawel J, Giezek H, Ahmed T, Chan CY. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006;17:1000–6.PubMed

105.

Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F. Efficacy and toilerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol. 2005;23:2822–30.PubMed

106.

Rapoport BL, Jordan K, Boice JA, Taylor A, Brown C, Hardwick JS, Carides A, Webb T, Schmoll H-J. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study. Support Care Cancer. 2010;18:423–31.PubMed

107.

Herrstedt J, Muss HB, Warr DG, et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy. Cancer. 2005;104:1548–55.PubMed

108.

Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol–EASE. J Clin Oncol. 2011;29:1495–501.PubMed

109.

Hesketh PJ, Rossi G, Rizzi G, 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;25:1340–6.PubMedPubMedCentral

110.

Aapro M, Rugo H, Rossi G, 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 chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014;25:1328–33.PubMedPubMedCentral

111.

Aapro M, Karthaus M, Schwartzberg L, Bondarenko I, Sarosiek T, Oprean C, Cardona-Huerta S, Hansen V, Rossi G, Rizzi G, Borroni ME, Rugo H. NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron. Support Care Cancer. 2017;25:1127–35.PubMed

112.

Gralla RJ, Bosnjak SM, Hontsa A, et al. A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Ann Oncol. 2014;25:1333–9.PubMedPubMedCentral

113.

Schwartzberg L, Roeland E, Andric Z, Kowalski D, Radic J, Voisin D, Rizzi G, Navari R, Gralla RJ, Karthaus M. Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy. Ann Oncol. 2018;29:1535–40.PubMed

114.

Schwartzberg L, Navari R, Clark-Snow R, Arkania E, Radyukova I, Patel K, Voisin D, Rizzi G, Wickham R, Gralla RJ, Aapro M, Roland E. Phase IIIB safety and efficacy of intravenous NEPA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with breast cancer receiving initial and repeat cycles of anthracycline and cyclophosphamide (AC) chemotherapy. Oncologist. 2020;25:e589–97.PubMed

115.

Rapoport B, Chua D, Poma A, Arora S, Wang Y, Fein LE. Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). Support Care Cancer. 2015;23:3281–8.PubMed

116.

Rapoport BL, Chasen MR, Gridelli C, Urban L, Modiano MR, Schnadig ID, Poma A, Arora S, Kansra V, Schwartzberg LS, Navari RM. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol. 2015;16:1079–89.PubMed

117.

Schwartzberg LS, Modiano MR, Rapoport BL, Chasen MR, Gridelli C, Urban L, Poma A, Arora S, Navari RM, Schnadig ID. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncol. 2015;16:1071–8.PubMed

118.

Navari RM. The safety of rolapitant for the treatment of nausea and vomiting associated with chemotherapy. Exp Opin Drug Saf. 2019;18:1127–32.

119.

Walton GD. Safety profile of HTX-019 administered as an intravenous push in cancer patients: a retrospective review. Adv Ther. 2019;36:662–9.PubMedPubMedCentral

120.

Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang H-M, Baranowski V. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin. 2007;23:533–43.PubMed

121.

Grimison R, Mersiades A, Kirby A, Lintzeris N, Morton R, Haber R, Olver I, Walsh A, McGregor I, Cheung Y, Tognela A, Hahn C, Briscoe K, Aghmesheh M, Fox P, Abdi E, Clarke S, Della-Fiorentina S, Shannon J, Gedye C, Begbie S, Simes J, Stockler M. Oral TCH: CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomized, placebo-controlled, phase 2 crossover trial. Ann Oncol. 2020;31:1553–60.PubMed

122.

Chow R, Valdez C, Chow N, Zhang D, Im J, Sodhi E, Lock M. Oral cannabinoid for the prophylaxis of chemotherapy-induced nausea and vomiting—a systematic review and meta-analysis. Support Care Cancer. 2020;28:2095–103.PubMed

123.

Bymaster FP, Rasmussen K, Calligaro DO, Nelson DL, DeLapp NW, Wong DT, Moore NA. In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug. J Clin Psychiatry. 1997;58(suppl 10):28–36.PubMed

124.

Navari RM, Einhorn LH, Passik SD, Loehrer PJ Sr, Johnson C, Mayer ML, McClean J, Vinson J, Pletcher W. A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier Oncology Group Study. Support Care Cancer. 2005;13:529–34.PubMed

125.

Navari RM, Einhorn LH, Loehrer PJ Sr, Passik SD, Vinson J, McClean J, Chowhan N, Hanna NH, Johnson CS. A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotheraåy-induced nausea and vomiting: a Hoosier Oncology Group Study. Support Care Cancer. 2007;15:1285–91.PubMed

126.

Yanai T, Iwasa S, Hashimoto H, Ohyanagi F, Takiguchi T, Takeda K, Nakao M, Sakai H, Nakayama T, Minato K, Arai T, Suzuki K, Shimada Y, Nagashima K, Terakado H, Yamamoto N. A randomized, double-blind phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy. Int J Clin Oncol. 2018;23:382–8.PubMed

127.

Tanaka K, Inui N, Karayama M, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Kusagaya H, Matsuura S, Uto T, Hashimoto D, Matsui T, Asada K, Suda T. Olanzapine-containing antiemetic therapy for the prevention of carboplatin-induced nausea and vomiting. Cancer Chemother Pharmacol. 2019;84:147–53.PubMed

128.

Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011;9:188–95.PubMed

129.

Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med. 2016;375:134–42.PubMedPubMedCentral

130.

Hashimoto H, Abe M, Tokuyama O, Mizutani H, Uchitomi Y, Yamaguchi T, Hoshina Y, Sakata Y, Takashi TY, Nakashima K, Nakao M, Takei D, Zenda S, Mizukami K, Iwasa S, Sakurai M, Yamamoto N, Ohe Y. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicenter, randomized, double-blind, placebo-controlled trial. Lancet Oncol. 2020;21:242–9.PubMed

131.

Chow R, Herrstedt J, Aapro M, Chiu L, Lam H, Prsic E, Lock M, DeAngelis C, Navari RM. Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting: a systematic review, meta-analysis, cumulative meta-analysis and fragility assessment of the literature. Support Care Cancer. 2021;29:3439–59.PubMed

132.

Zhou J-G, Huang L, Jin S-H, Xu C, Frey B, Ma H, Gaipl US. Olanzapine combined with 5-hydroxytryptamine type 3 receptor antagonisy (5-HT3RA) plus dexamethasone for prevention and treatment of chemotherapy-induced nausea and vomiting in high and moderate emetogemic chemotherapy: a systematic review and meta-analysis of randomized controlled trials. ESMP Open. 2020;5: e000621. https://doi.org/10.1136/esmoopen-2019-000621.CrossRef

133.

Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, Clark-Snow RA, Dupuis LL, Einhorn LH, Feyer P, Hesketh PJ, Jordan K, Olver I, Rapoport BL, Roscoe J, Ruhlmann CH, Walsh D, Warr D, Van der Wetering M, on behalf of the participants of 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. 2016;27:v119–33.PubMed

134.

MASCC/ESMO Antiemetic Guideline 2016 with updates in 2019. https://mascc.memberclicks.net/mascc-guidelines. Accessed 23 Aug 2021.

135.

Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis L, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Lyman GH. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38:2782–97.PubMed

136.

Antiemesis: Version 1.2021. Ettiner DS, Berger MJ, Anand S, Babour S, Bergsbaken J, Brandt D, Brown GE, Crews JR, Hong C, Kim EJ, Kirkegaard S, Kloth DD, Klute K, Kris MG, Lim D, Ma CX, Maurer V, McAlister RK, Mehta R, Noonan K, Riebrandt G, Roeland E, Rogers JE, Rugo HS, Saunders I, Scullion B, Silveira M, Wolf A. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed 30 Aug 2021.

137.

Martin M, Diaz-Rubio E, Sanchez A, Almenarez J, López-Vega JM. The natural course of emesis after carboplatin treatment. Acta Oncol. 1990;29:593–5.PubMed

138.

Ludmir EB, Mainwaring W, Lin TA, Miller AB, Jethanandani A, Espinoza AF, Mandel JJ, Lin SH, Smith BD, Smith GL, VanderWalde NA, Minsky BD, Koong AC, Stinchcombe TE, Jagsi R, Gomez DR, Thomas CR, Fuller CD. Factors associated with age disparities among cancer clinical trial participants. JAMA Oncol. 2019;5:1769–73.PubMed

139.

Lackman M, Vickers MM, Hsu T. Physician-reported reasons for non-enrollment of older adults in cancer clinical trials. J Geriatr Oncol. 2020;11:31–6.PubMed

140.

Malakoff D. Spiraling costs threaten gridlock. Science. 2008;322:210–3.PubMed

141.

Celio L, Bonizzoni E, Bajetta E, Sebastiani S, Perrone T, Aapro MS. Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials. Support Care Cancer. 2013;21:565–73.PubMed

142.

Ito Y, Tsuda T, Minatogawa H, Kano S, Sakamaki K, Ando M, Tsugawa K, Kojima Y, Furuya N, Matsuzaki K, Fukuda M, Sugae S, Ohta I, Arioka H, Tokuda Y, Narui K, Tsuboya A, Suda T, Morita S, Boku N, Yamanaka T, Nakajima TE. Placebo-controlled, double-blind phase III study comparing dexamethasone on day 1 with dexamethasone on days 1 to 3 with combined neurokinin-1 receptor antagonist and palonosetron in high-emetogenic chemotherapy. J Clin Oncol. 2018;36:1000–6.PubMed

143.

Celio L, Cortinovis D, Cogoni AA, Cavanna L, Martelli O, Carnio S, Collova E, Bertolini F, Petrelli F, Cassano A, Chiari R, Zanelli F, Pisconti S, Vittimberga I, Letizia A, Misino A, Gernone A, Bonizzoni E, Pilotto S, De Placido S, Bria E. Dexamethasone-sparing regimens with oral netupitant and palonosetron for the prevention of emesis caused by high-dose cisplatin: a randomized non-inferiority study. Oncologist. 2021. https://doi.org/10.1002/onco.13851.CrossRefPubMedPubMedCentral

144.

Hayashi T, Shimokawa M, Mizuki F, Matsuo K, Kawada K, Nakano T, Egawa T. Efficacy of one-day versus multiple-day dexamethasone for chemotherapy-induced nausea and vomiting in lung cancer patients receiving carboplatin-based chemotherapy: a propensity score-matched analysis. Support Care Cancer. 2021;29:5029–35.PubMed

145.

Janowitz T, Kleeman S, Vonderheide RH. Reconsidering dexamethasone for antiemesis when combining chemotherapy and immunotherapy. Oncologist. 2021;26:269–73.PubMedPubMedCentral

146.

Grant RC, Rotstein C, Liu G, Forbes L, Vu K, Lee R, Ng P, Krzyzanowska M, Warr D, Knox J. Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada. Support Care Cancer. 2020;28:5031–6.PubMedPubMedCentral

147.

Chapell R, Aapro MS. Efficacy of aprepitant among patients aged 65 and over receiving moderately to highly emetogenic chemotherapy: a meta-analysis of unpublished data from previously published studies. J Geriatr Oncol. 2013;4:73–83.

148.

Aapro M, Jordan K, Gralla RJ, Rizzi G, Rossi G, Palmas M, Alyasova AV, Lisyanskaya AS, Bosnjak S, Hesketh PJ. Safety and efficacy of NEPA, an oral fixed combination of netupitant and palonosetron in older patients. J Geriatr Oncol. 2017;8:56–63.PubMed

Titel: Prevention of Chemotherapy-Induced Nausea and Vomiting in the Older Patient: Optimizing Outcomes
verfasst von: Jørn Herrstedt
Sanne Lindberg
Peter Clausager Petersen
Publikationsdatum: 09.12.2021
Verlag: Springer International Publishing
Erschienen in: Drugs & Aging / Ausgabe 1/2022
Print ISSN: 1170-229X
Elektronische ISSN: 1179-1969
DOI: https://doi.org/10.1007/s40266-021-00909-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Prevention of Chemotherapy-Induced Nausea and Vomiting in the Older Patient: Optimizing Outcomes

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

Vorsicht, erhöhte Blutungsgefahr nach PCI!

Wie managen Sie die schmerzhafte diabetische Polyneuropathie?

Update Innere Medizin

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2022

Clinical Considerations for Insulin Therapy in Older Adults with Type 1 Diabetes

Frequency and Acceptance of Clinical Decision Support System-Generated STOPP/START Signals for Hospitalised Older Patients with Polypharmacy and Multimorbidity

Highly Variable Paracetamol Pharmacokinetics After Multiple Oral Dosing in Frail Older People: A Population Pharmacokinetic Analysis

Non-Steroidal Anti-Inflammatory Drugs and Risk of Acute Kidney Injury and Hyperkalemia in Older Adults: A Retrospective Cohort Study and External Validation of a Clinical Risk Model

The Effect of Aspirin on the Primary Prevention of Major Adverse Cardiac and Cerebrovascular Events in Chinese Older Adults: A Registration Study

Management of Hyperglycemia in Older Adults with Type 2 Diabetes

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

Vorsicht, erhöhte Blutungsgefahr nach PCI!

Wie managen Sie die schmerzhafte diabetische Polyneuropathie?

Update Innere Medizin