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

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