Design and Development of New Combinations of the CMF Agents with Taxanes (Paclitaxel or Docetaxel) in Advanced Breast Cancer: A Feasibility Study

Abstract

Aims and background

We previously designed and tested combinations made up of the CMF agents, two at a time by rotation, and of doxorubicin or epirubicin. The present study was aimed to similarly test new combinations made up of the CMF agents, two at a time by rotation, and paclitaxel or docetaxel.

Methods

The doses of each taxane were escalated with the objective of reaching at least a single dose level of 90 mg/m² of paclitaxel and 45 mg/m² of docetaxel on days 1 and 8 of each four-week cycle. Thirty-two patients with advanced breast carcinoma were randomized to receive increasing doses of paclitaxel (45, 65, 80, 90 and 100 mg/m²) or docetaxel (30, 35, 40, 45 and 50 mg/m²) together with the CMF agents at the same dose as that used in the conventional regimen. Each dose level was administered to a triplet of patients. No direct comparison of the two taxanes was made.

Results

The fourth dose level was reached for paclitaxel and docetaxel. The most important toxicities were grade 4 neutropenia and grade 1-2 nausea/vomiting and stomatitis. The objective response rate, assessed only after the third cycle at any dose level, was 31% (95% CI, 15-47%).

Conclusions

The combinations of the CMF agents (two at a time in rotation) with paclitaxel (90 mg/m²) or docetaxel (45 mg/m²) on days 1 and 8 of each four-week cycle are feasible and lead to definite signs of therapeutic activity, and the side effects are generally mild. Further studies are therefore warranted.