title: A randomized phase 2 study comparing EC or CMF versus nab-paclitaxel plus capecitabine as adjuvant chemotherapy for nonfrail elderly patients with moderate to high-risk early breast cancer (ICE II-GBG 52).
abstract: BACKGROUND
  Although greater than 40% of breast cancers occur in patients aged ≥65 years, these individuals are frequently undertreated. Taxane-based adjuvant chemotherapy is considered the treatment of choice but to the authors' knowledge has only limited evidence in elderly patients.
  
  
  METHODS
  Patients aged ≥65 years with a Charlson comorbidity index ≤2 and pT1/2 pN0/1 disease and either human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative, grade 3 (according to Common Terminology Criteria for Adverse Events [version 3.0]), high uPA/PAI-1 or any stage pT3/4 pN2/3 breast cancer were randomized to receive 4 cycles of adjuvant epirubicin and cyclophosphamide (EC) (epirubicin at a dose of 90 mg/m(2) and cyclophosphamide at a dose of 600 mg/m(2) intravenously [iv] on day 1 every 3 22 days) or 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (cyclophosphamide at a dose of 500 mg/m(2), methotrexate at a dose of 40 mg/m(2), and 5-fluorouracil at a dose of 600 mg/m(2) iv on days 1 plus 8 every 29 days) versus 6 cycles of nab-paclitaxel and capecitabine (nPX) (nab-paclitaxel at a dose of 100 mg/m(2) iv on days 1, 8, and 15 every 21 days with 1 week of rest every 6 weeks plus capecitabine at a dose of 2000 mg/m(2) orally on days 1-14 every 21 days). Primary endpoints were treatment discontinuations and overall frequency of adverse events.
  
  
  RESULTS
  Thirteen of 198 patients (6.6%) discontinued EC/CMF and 69 of 193 patients (35.8%) discontinued nPX (P<.001) with 1 and 5 deaths observed during treatment, respectively. Grade 3 to 5 adverse events were more frequent among patients treated with EC/CMF (90.9%) than among those treated with nPX (64.8%) (P<.001), with hematological toxicities being more frequent with EC/CMF (88.4% vs 22.3%; P<.001), but nonhematological toxicities (hand-foot syndrome, diarrhea, mucositis, fatigue, sensory neuropathy, thromboembolisms, and metabolic disorders) being more frequent with nPX (58.5% vs 18.7%; P<.001). None of the geriatric scores (Charlson comorbidity index, Vulnerable Elders Survey [VES-13], Instrumental Activities of Daily Living [IADL], and G8) independently predicted grade 3 to 5 toxic events or treatment discontinuations. No differences in survival between the treatment groups were observed after 22.8 months.
  
  
  CONCLUSIONS
  Compared with EC/CMF, treatment with nPX led to more treatment discontinuations and nonhematological toxicities in elderly patients with moderate or high-risk breast cancer.
authors.affiliation: German Breast Group, Neu-Isenburg, Germany.|Department of Gynecology and Obstetrics, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.affiliation: Elisabeth Hospital, Kassel, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Conrad
authors.affiliation: Department Obstetrics and Gynecology, Sudstadt Clinic, Rostock, Germany.
authors.forename: Toralf
authors.initials: T
authors.lastname: Reimer
authors.affiliation: Study Centre Oncology, Ravensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Kiel, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.affiliation: Interdisciplinary Centre Munich, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.affiliation: Department of Obstetrics and Gynecology, Marienhospital, Witten, Germany.
authors.forename: John
authors.initials: J
authors.lastname: Hackmann
authors.affiliation: Department of Obstetrics and Gynecology, Hoechst Clinic, Frankfurt, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Möbus
authors.affiliation: University Women's Hospital, Heidelberg, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.affiliation: Department of Obstetrics and Gynecology, Ev. Waldkrankenhaus Hospital, Berlin, Germany.
authors.forename: Jochem
authors.initials: J
authors.lastname: Potenberg
authors.affiliation: University Women's Hospital, Freiburg, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
authors.affiliation: Department of Obstetrics and Gynecology, Kreiskrankenhaus Torgau, Torgau, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Simon
authors.affiliation: University Women's Hospital, Halle, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thomssen
authors.affiliation: University Women's Hospital, Ulm, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.affiliation: Berlin Charity Hospital, Institute of Pathology, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.affiliation: Institute of Pathology Kaufbeuren-Ravensburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Alfer
authors.affiliation: Department of Gynecology Obstetrics and Gynecology, Sana Clinic, Offenbach, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.affiliation: German Breast Group, Neu-Isenburg, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nekljudova
authors.affiliation: German Breast Group, Neu-Isenburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Burchardi
authors.affiliation: German Breast Group, Neu-Isenburg, Germany.|Department of Gynecology Obstetrics and Gynecology, Sana Clinic, Offenbach, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D015251:Epirubicin; D000069287:Capecitabine; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate
keywords: adjuvant chemotherapy; capecitabine; early breast cancer; elderly patients; nab-paclitaxel