title: Trade-offs in quality of life and survival with chemotherapy for advanced breast cancer: mature results of a randomized trial comparing single-agent mitoxantrone with combination cyclophosphamide, methotrexate, 5-fluorouracil and prednisone.
abstract: BACKGROUND
  We evaluate trade-offs between quality of life (QoL) and survival improvement for two chemotherapy regimens in advanced breast cancer. We also report on the long-term survival of patients in the ANZ 8614 clinical trial.
  
  
  METHODS
  A total of 391 patients were randomized to mitoxantrone (14 mg/m(2) intravenously every 21 days) or a combination of cyclophosphamide 100 mg/m(2) and prednisone 40 mg/m(2) orally days 1 to 14 plus methotrexate 40 mg/m(2) and 5-fluorouracil 600 mg/m(2) intravenously days 1 and 8 every 28 days (CMFP). QoL was self-assessed on 14 linear analog scales. We computed the mean differences between the two treatments as products of the mean differences in global QoL, progression-free survival and overall survival.
  
  
  RESULTS
  CMFP led to a higher overall tumor response (39% vs. 25%, P=0.004) and longer progression-free survival (PFS) (median 5.6 vs 3.9 months, P=0.02) but with significantly more toxicity from alopecia, mucositis, diarrhea, anemia and lethargy. Overall survival (OS) was similar in the two groups (median 10.1 vs 11.6 months, P=0.81). QoL over the first 12 weeks was rated better by patients on CMFP for mood (P=0.04), nausea and vomiting (P=0.01), and feeling sick (P=0.02) but worse for hair loss (P<0.0001). A weighted combination of individual QoL items favoured CMFP (subset score mean difference 2.4, P=0.03). A global QoL score tended to favour CMFP (global score mean difference 1.7, P=0.18). Quality-adjusted PFS was significantly longer with CMFP (mean 7.208 vs 5.965 months, P=0.04), but quality-adjusted OS was not significantly different (mean 11.832 vs 11.315 months, P=0.57).
  
  
  CONCLUSIONS
  Despite the greater toxicity, the superior antitumor activity of CMFP led to an overall improvement in quality-adjusted PFS. In advanced breast cancer, in clinical decision making about treatment for palliative intent, the principle used to assess trade-offs between antitumor efficacy and toxicity remains relevant and applicable to all modern therapeutic agents.
authors.affiliation: ANZ BCTG Statistical Centre, NHMRC Clinical Trials Centre, Sydney, Australia ; ANZ BCTG Statistical Centre, NHMRC Clinical Trials Centre, Sydney, Australia.
authors.forename: Chee Khoon
authors.initials: CK
authors.lastname: Lee
authors.forename: Val J
authors.initials: VJ
authors.lastname: Gebski
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Veillard
authors.forename: Vernon
authors.initials: V
authors.lastname: Harvey
authors.forename: Martin Hn
authors.initials: MH
authors.lastname: Tattersall
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Byrne
authors.forename: Brian
authors.initials: B
authors.lastname: Brigham
authors.forename: John
authors.initials: J
authors.lastname: Forbes
authors.forename: R John
authors.initials: RJ
authors.lastname: Simes
keywords: Breast cancer; Chemotherapy; Quality of life; Randomized trial; Survival; Toxicity
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