Randomized trial to compare the efficacy and toxicity of cyclophosphamide,methotrexate and 5-fluorouracil (CMF) with methotrexate mitoxantrone (MM) in advanced carcinoma of the breast

One hundred and sixteen patients with locally advanced or metastatic breast cancer were randomized to receive CMF (cyclophosphamide 600 mg m(-2) day 1 and 8 i.v., 5-fluorouracil 600 mg m(-2) day 1 and 8 i.v.,, methotrexate 40 mg m(-2) day 1 and 8 i.v., monthly for 6 cycles) or MM (methotrexate 30 mg m(-2), mitoxantrone 6.5 mg m(-2), both i.v. day 1 3-weekly for 8 cycles) a s first line treatment with chemotherapy Objective responses occurred in 17 patients out of 58 (29%) who received CMF and nine out of 58 (15%) who rec eived MM; 95% confidence interval for difference in response rates (-1%-29% ), P = 0.07. No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged. There was, however, significantly reduced haematological toxicity (P < 0.00 1) and alopecia (P < 0.001) and fewer dose reductions and delays in patient s randomized to MM. No statistically significant differences were seen betw een the two regimes in terms of quality of life (QOL). However, some associ ation between QOL and toxicity was apparent overall with pooled QOL estimat es tending to indicate a worsening in psychological state with increasing m aximum toxicity over treatment. Despite the fact that results surrounding r esponse rates and time to progression did not reach statistical significanc e, their possible compatibility with an improved outcome on CMF treatment m ust be borne in mind. However, MM is a well-tolerated regimen with fewer si de-effects than CMF, which with careful patient management and follow-up, t herefore, may merit consideration as a first-line treatment to palliate pat ients with metastatic breast cancer who are infirm or elderly. (C) 1999 Can cer Research Campaign.