title: Alopecia as surrogate marker for chemotherapy response in patients with primary epithelial ovarian cancer: a metaanalysis of four prospective randomised phase III trials with 5114 patients.
abstract: OBJECTIVE
  Alopecia is a common side-effect of chemotherapy and affects quality of life of cancer patients. Some patients and physicians believe that alopecia could be a surrogate marker for response to chemotherapy and impact on prognosis. However, this was never been tested in a sufficiently large cohort of ovarian cancer patients.
  
  
  METHODS
  We analysed retrospectively the meta-databank of four prospective randomised phase-III-trials with platinum- and taxane-based 1st-line-chemotherapy in patients with advanced epithelial ovarian cancer (EOC) regarding the impact of alopecia overall outcome.
  
  
  RESULTS
  For 4705 (92.0%) of a total of 5114 EOC-patients alopecia was documented. They had received on median six cycle platinum-taxane chemotherapy (range 0-11) with 4186 (89.0%) having completed ⩾ 6 cycles. Worst alopecia grade was 0 in 2.4%, 1 in 2.9% and 2 in 94.7% of the patients. In a univariate analysis, including all patients, grade-0/1 alopecia was associated with significantly lower progression free survival (PFS) and overall survival (OS) compared to grade-2 alopecia. However when assessing only those patients who completed ⩾ 6 chemotherapy-cycles and hence eliminating the bias of lower total dose of treatment, alopecia failed to retain any significant impact on survival in the multivariate analysis. Merely the time point of alopecia onset was an independent prognostic factor of survival: patients who developed grade-2 alopecia up to cycle 3 had a significantly longer OS compared to patients who experienced alopecia later during therapy (hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.04-1.50).
  
  
  CONCLUSIONS
  Within a large EOC-patient cohort with 1st-line platinum- and taxane-based chemotherapy early onset alopecia appears to be significantly associated with a more favourable outcome in those patients who completed ⩾ 6 chemotherapy cycles. It remains to be elucidated if early onset alopecia is just a surrogate marker for higher sensitivity to chemotherapy or if other biological effects are underlying.
authors.affiliation: Department of Gynecology, University of Berlin, Charite, Campus Virchow, Berlin, Germany. Electronic address: Jalid.Sehouli@charite.de.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Department of Gynecology, University of Berlin, Charite, Campus Virchow, Berlin, Germany; Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: Fotopoulou
authors.affiliation: Department of Gynecology, University of Berlin, Charite, Campus Virchow, Berlin, Germany.
authors.forename: Edibe
authors.initials: E
authors.lastname: Erol
authors.affiliation: Department of Gynecology, University of Berlin, Charite, Campus Virchow, Berlin, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Richter
authors.affiliation: Coordinating Center for Clinical Trials, University Marburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Reuss
authors.affiliation: Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.affiliation: Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Eric Pujade
authors.initials: EP
authors.lastname: Lauraine
authors.affiliation: Nordic Society of Gynaecological Oncology (NSGO) and Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kristensen
authors.affiliation: Department of Oncology, Odense University Hospital, 5000 Odense, Denmark.
authors.forename: Jörn
authors.initials: J
authors.lastname: Herrstedt
authors.affiliation: Gynäkologie & Gynäkologische Onkologie, Kliniken Essen-Mitte, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.affiliation: Zentrum für Gynäkologische Onkologie, Kiel, Germany.
authors.forename: Jacobus
authors.initials: J
authors.lastname: Pfisterer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D014408:Biomarkers, Tumor; D000077216:Carcinoma, Ovarian Epithelial; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D011379:Prognosis; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin
keywords: Association; Chemotherapy; Epithelial ovarian cancer; Responds; Survival; Therapy effectiveness