title: First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer. Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88.
abstract: BACKGROUND
  In a phase III randomized trial, we compared the effectiveness and tolerability of fadrozole (CGS 16949A), a non-steroidal aromatase inhibitor, to tamoxifen as first-line endocrine therapy in postmenopausal women with advanced breast cancer.
  
  
  METHODS
  Two hundred twelve eligible patients were randomized to receive tamoxifen 20 mg daily, or fadrozole 1 mg twice daily orally until disease progression or the advent of undue toxicity. The treatments were to be discontinued upon disease progression.
  
  
  RESULTS
  Prognostic factors were well balanced between the treatment groups, except for sites of metastatic disease. Fadrozole-treated patients had significantly more visceral, especially liver, involvement and less bone-dominant disease. Response rates for fadrozole and tamoxifen were similar, 20% and 27% (95% Confidence Limits (CL): 13%-29% and 21%-35%), respectively. Time to treatment failure was longer in patients randomized to tamoxifen (8.5 months for tamoxifen vs. 6.1 months for fadrozole), but did not reach statistical significance after adjustment for prognostic factors (P = 0.09). Fadrozole, for which a significantly lower percentage of clinically relevant toxic effects (WHO toxicity grade > or = 2) was recorded (27% vs. 13%, respectively; P = 0.009), was better tolerated than tamoxifen. Severe cardiovascular events including 3 fatalities were seen only in patients treated with tamoxifen. Eighty-two patients crossed over to tamoxifen and 66 patients to fadrozole. Crossover endocrine therapy led to response or stable disease in 64% of the patients. The overall survival times of the two treatment groups were similar.
  
  
  CONCLUSIONS
  Fadrozole and tamoxifen showed similar efficacy as first-line treatments in postmenopausal patients with advanced breast cancer. Fadrozole was significantly better tolerated and may therefore be an appropriate alternative to tamoxifen, especially for patients predisposed to thromboembolic events.
authors.affiliation: Department of Internal Medicine C, Kantonsspital, St. Gallen, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
authors.forename: K
authors.initials: K
authors.lastname: Beretta
authors.forename: M
authors.initials: M
authors.lastname: Bacchi
authors.forename: M
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: W F
authors.initials: WF
authors.lastname: Jungi
authors.forename: F
authors.initials: F
authors.lastname: Cavalli
authors.forename: H J
authors.initials: HJ
authors.lastname: Senn
authors.forename: M
authors.initials: M
authors.lastname: Fey
authors.forename: T
authors.initials: T
authors.lastname: Löhnert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D017316:Fadrozole / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D013629:Tamoxifen; D017316:Fadrozole