Randomized trial comparing cyclophosphamide, methotrexate, and 5–fluorouracil (CMF) with rotational CMF, epirubicin and vincristine as primary chemotherapy in operable breast carcinoma

Abstract

BACKGROUNDAccording to the overview of Early Breast Cancer Trialists' Collaborative Group, anthracycline containing regimens are superior to cyclophosphamide, methotrexate, and 5–fluorouracil (CMF) as adjuvant chemotherapy for breast carcinoma, but no comparative information is available in terms of primary chemotherapy. In the current randomized controlled trial, the authors compared CMF with a chemotherapy regimen including CMF, epirubicin, and vincristine (CMFEV).METHODSTwo hundred eleven patients with Stages I and II palpable breast carcinoma and tumor diameter > 2.5 cm or ≤ 2.5 cm with cytologically proven axillary lymph node involvement were randomized to receive CMF (arm A) or CMFEV regimen (arm B) for four cycles before surgery. After surgery, patients in both arms received adjuvant CMF for three cycles; the postmenopausal patients also received tamoxifen for two years.RESULTSThere were no significant differences in the complete response (CR) and in the CR plus partial response (PR) rates between the two arms. In the subset analysis, among premenopausal patients, significantly higher rates of CR (26% vs 4%, P = 0.004) and of CR + PR rates (80% vs 54%, P = 0.007) were observed in the CMFEV, as compared to the CMF arm. Multivariate analysis confirmed the presence of a significant interaction between menopausal status and type of treatment on the probability of achieving CR (P = 0.02) or CR + PR (P = 0.01). There were no major differences in the side effects of the two treatments, with the exception of more frequent alopecia in the experimental arm.CONCLUSIONSThe results of the current study are in line with those of previous published randomized clinical trials comparing regimens without and with anthracycline as adjuvant treatment, indicating an agreement between the short term response to primary chemotherapy and the long term results observed in the adjuvant setting. Cancer 2002;95:228–35. © 2002 American Cancer Society.DOI 10.1002/cncr.10678

Randomized Trial Comparing Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF) Regimen with Rotational CMFEV Regimen (E=Epirubicin, V=Vincristine) as Adjuvant Chemotherapy in Moderate Risk Operable Breast Carcinoma

“…These differences in terms of recurrence and death, although not statistically significant, offer evidence of a potential major efficacy of the CMFEV compared to the CMF regimen. This efficacy was, at least in part, more clearly showed in our previous study on neo-adjuvant chemotherapy where, on a short term evaluation, the rate of clinical responses, both complete (CR) and complete plus partial (PR), were significantly higher in the subset of pre-menopausal patients treated with CMFEV compared to those treated with CMF [10]. Similarly, on a long-term evaluation, again in the subset of pre-menopausal patients, the proportion of RFS tended to be higher and the proportion of LRRFS was significantly higher in the CMFEV arm compared to the CMF arm, thus mirroring the short-term response results [11].…”

“…Indeed in the first study, the superiority of CMFEV regimen, as short term objective response, was seen only in premenopausal and not in post-menopausal patients; in addition, in a multivariate analysis, a significant interaction was confirmed between the menopausal status and the type of treatment on the probability to obtain CR or CR plus PR [10]. In the present study, a significant correlation was observed between the estrogen and/or progesterone receptor status and the type of regimen; CMFEV was more effective, in terms of OS and RFI, in patients with positive ER and/or PgR tumors but not in patients with both negative ER and PgR tumors.…”

“…In the first occasion, the comparison was developed in a neoadjuvant settings [10,11]; in the present second occasion, the comparison was developed in an adjuvant settings. Therefore such comparison presents, by itself, some similarities but also some substantial differences.…”

“…Firstly, these differences are related to the therapeutic scheme utilized, which refers to the different treatment settings. Moreover, in the neoadjuvant settings, the comparison of the therapeutic results could be done both on a short term, based on the evaluation of objective therapeutic response [10], as well as on a long term, based on the outcome [11]. In the adjuvant settings the comparison was possible only on a long term.…”

“…It was first designed and tested by our Group as a means of late intensification after CMF in metastatic breast carcinoma [9] and then in the neoadjuvant setting of operable breast carcinoma [10,11]. Its rotational strategy is different from that of alternating or sequential schemes as the five agents are administered at full dose but, in order to avoid excessive toxicity and consequent dose reductions, each cycle involves the administration of only four drugs, always including vincristine (V) and epirubicin (E).…”