title: A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG.
abstract: BACKGROUND
  Prospective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial.
  
  
  METHODS
  Patients were randomized to six cycles of PLD (45 mg/m(2) every 4 weeks) or eight cycles of capecitabine (1000 mg/m(2) twice daily, day 1-14 every 3 weeks).
  
  
  RESULTS
  The study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively.
  
  
  CONCLUSIONS
  Both PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully.
  
  
  BACKGROUND
  EudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.
authors: Department of Internal Medicine, Medical Center Alkmaar, Alkmaar. Electronic address: c.smorenburg@nki.nl.
authors: C H
authors: CH
authors: Smorenburg
authors: Comprehensive Cancer Center the Netherlands, Amsterdam.
authors: S M
authors: SM
authors: de Groot
authors: BOOG Study Center, Dutch Breast Cancer Research Group BOOG, Amsterdam.
authors: A E
authors: AE
authors: van Leeuwen-Stok
authors: Department of Geriatric Medicine, Diakonessenhuis, Utrecht.
authors: M E
authors: ME
authors: Hamaker
authors: Department of Internal Medicine, Medisch Spectrum Twente, Enschede.
authors: A N
authors: AN
authors: Wymenga
authors: Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden.
authors: H
authors: H
authors: de Graaf
authors: Department of Internal Medicine, Ikazia Hospital, Rotterdam.
authors: F E
authors: FE
authors: de Jongh
authors: Department of Internal Medicine, Vlietland Hospital, Schiedam.
authors: J J
authors: JJ
authors: Braun
authors: Department of Internal Medicine, St. Antonius Hospital, Nieuwegein.
authors: M
authors: M
authors: Los
authors: Department of Internal Medicine, Reinier de Graaf Hospital, Delft.
authors: E
authors: E
authors: Maartense
authors: Biometrics Department, Netherlands Cancer Institute, Amsterdam.
authors: H
authors: H
authors: van Tinteren
authors: Department of Medical Oncology, Leiden University Medical Center, Leiden.
authors: J W R
authors: JWR
authors: Nortier
authors: Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors: C
authors: C
authors: Seynaeve
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009426:Netherlands; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D000069287:Capecitabine; D004317:Doxorubicin; D005472:Fluorouracil
keywords: capecitabine; elderly; geriatric; metastatic breast cancer; pegylated liposomal doxorubicin; phase III