title: The influence of comorbidity and comedication on grade III/IV toxicity and prior discontinuation of chemotherapy in recurrent ovarian cancer patients: An individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO).
abstract: BACKGROUND
  Ovarian cancer is usually a cancer of the older age group. Comorbidities and comedications increase with rising age. Aim of this study was to evaluate association of comorbidity and comedication with grade III/IV toxicities and prior cessation of chemotherapy in ovarian cancer patients.
  
  
  METHODS
  As an individual participant data meta-analysis this study analyzes the original data of three phase II/III chemotherapy studies of the North-Eastern German Society of Gynecological Oncology (NOGGO). Risk scores for certain combinations of risk factors were calculated based on stepwise regression analyses.
  
  
  RESULTS
  Altogether, 1213 patients were included in the study. Cardiovascular disease was the most frequent comorbidity (47.5%). In multivariate analyses it was associated with hematological, non-hematological, pulmonary and renal grade III/IV toxicities (p=0.002; p<0.001; p=0.005; p<0.001). Renal toxicity was more frequent when using diuretics and ACE-inhibitors (p<0.001; p=0.002). Prior cessation of therapy was e.g. associated with use of diuretics, insulin and digitalis (p=0.001; p=0.04; p=0.03). The risk for renal grade III/IV toxicities was more than 16 times higher when using both a diuretic and an ACE-inhibitor.
  
  
  CONCLUSIONS
  Regimens of ovarian cancer treatment should not be restricted to direct cancer therapy but rather include additional individualized treatment of comorbidities. Comedications such as diuretics increase grade III/IV toxicities and patients at risk should be closely monitored.
authors.affiliation: European Competence Center for Ovarian Cancer (EKZE), Department of Gynecology, Charité - University Medicine of Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany; Dresden International University, Division of Health Care Sciences, Center for Clinical Research and Management Education, Freiberger Str. 37, 01067 Dresden, Germany. Electronic address: hannah.woopen@charite.de.
authors.forename: H
authors.initials: H
authors.lastname: Woopen
authors.affiliation: European Competence Center for Ovarian Cancer (EKZE), Department of Gynecology, Charité - University Medicine of Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Richter
authors.affiliation: European Competence Center for Ovarian Cancer (EKZE), Department of Gynecology, Charité - University Medicine of Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Chekerov
authors.affiliation: Dresden International University, Division of Health Care Sciences, Center for Clinical Research and Management Education, Freiberger Str. 37, 01067 Dresden, Germany; Department of Neurology, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Siepmann
authors.affiliation: European Competence Center for Ovarian Cancer (EKZE), Department of Gynecology, Charité - University Medicine of Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Ismaeel
authors.affiliation: European Competence Center for Ovarian Cancer (EKZE), Department of Gynecology, Charité - University Medicine of Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: jalid.sehouli@charite.de.
authors.forename: J
authors.initials: J
authors.lastname: Sehouli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015897:Comorbidity; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
keywords: Comedication; Comorbidity; Discontinuation of chemotherapy; Ovarian cancer; Toxicity