Comparison of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) with a rotational crossing and a sequential intensification regimen in advanced breast cancer - A prospective randomized study

The Italian Oncology Group for Clinical Research tested two experimental ch emotherapy strategies in an attempt to improve the results achievable with conventional chemotherapy in metastatic breast cancer. One hundred sixty-tw o patients were randomly allocated as follows: (a) to the conventional cycl ophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen (CMF); (b) to a rotational crossing program (ROT-CROSS); or (c) to a sequential intens ification program (SEQ-INT). The same single agents (C, M, F, cisplatin, et oposide, and doxorubicin) were administered in both experimental arms, but following a different policy. The SEQ-INT program induced a significantly h igher complete response (32% vs. 6%, p = 0.0006) and objective response rat e (72% vs. 42%, p = 0.0047) than CMF did. There were no differences in surv ival between CMF and either experimental arm. A number of side effects were significantly more with both experimental chemotherapies than with CMF, bu t the treatments were generally tolerable. Although some caution is require d when interpreting a significant advantage found between an entire chemoth erapeutic strategy and a single conventional combination, this study docume nts the potential therapeutic advantage of administering different sequenti al chemotherapies, and changing each at the time of maximum result without waiting for a progression. The impressive cytoreductive effects achievable with this policy (SEQ-INT) in metastatic disease merit further investigatio n in the adjuvant setting.