Advanced breast cancer: a randomized study of doxorubicin or mitoxantrone in combination with cyclophosphamide and...

Drug selection for the treatment of advanced breast cancer is based on both efficacy and toxicity. Combination chemotherapy produces higher response rates than single agents, of which doxorubicin is the most active. This study compares efficacy and toxicity of the drugs doxorubicin and mitoxantrone when used as part of a 3 drug combination. Doxorubicin is the most active agent, but also one of the most toxic, and in this study was compared, in a 3-drug combination, with mitoxantrone with the aim of achieving comparable efficancy with reduced toxicity.

110 patients with advanced breast cancer previously untreated by chemotherapy were randomized to receive cyclophosphamide and vincristine, together with either doxorubicin 50 mg/m2 i.v. (VAC) or mitoxantrone 10 mg/m2 (VNC) for up to 6 cycles.

Of 53 eligible patients randomized to VAC, the overall response rate was 55% (CR rate 17%), while of 55 patients randomized to VNC the overall response rate was 42% (CR rate 7%). The difference is not statistically significant (p = 0.07), but there was a trend towards a higher response rate to VAC in patients aged less than 60, those with nodal and soft tissue disease, and those with 2 or more sites of disease. The principal difference in toxicity was reduced alopecia in favour of VNC. However there was also an increased number of deaths within the first cycle in patients randomized to VAC. There were no differences in survival, relapse free interval, or freedom from progression between the two arms.

Both VAC and VNC are effective regimens in advanced breast cancer. While the confidence limits in this study mean the response rate advantages of VAC could have arisen by chance, younger patients with adverse prognostic factors may warrant consideration of the VAC regimen.