Comparison of CMF (Cyclophosphamide, Methotrexate, and 5-Fluorouracil) With a Rotational Crossing and a Sequential Intensification Regimen in Advanced Breast Cancer

Abstract

The Italian Oncology Group for Clinical Research tested two experimental chemotherapy strategies in an attempt to improve the results achievable with conventional chemotherapy in metastatic breast cancer. One hundred sixty-two patients were randomly allocated as follows: (a) to the conventional cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen (CMF); (b) to a rotational crossing program (ROT-CROSS); or (c) to a sequential intensification program (SEQ-INT). The same single agents (C, M, F, cisplatin, etoposide, and doxorubicin) were administered in both experimental arms, but following a different policy. The SEQ-INT program induced a significantly higher complete response (32% vs. 6%, p = 0.0006) and objective response rate (72% vs. 42%, p = 0.0047) than CMF did. There were no differences in survival between CMF and either experimental arm. A number of side effects were significantly more with both experimental chemotherapies than with CMF, but the treatments were generally tolerable. Although some caution is required when interpreting a significant advantage found between an entire chemotherapeutic strategy and a single conventional combination, this study documents the potential therapeutic advantage of administering different sequential 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 investigation in the adjuvant setting.

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo

“…However, the highly successful BC chemotherapeutic agents, including doxorubicin/epirubicin, docetaxel, and paclitaxel [ 6 , 7 ], target early-stage tumors. Advanced stage BCs are managed by carboplatin, cisplatin, gemcitabine, capecitabine, vinorelbine, abraxane [ 8 , 9 , 10 ], or combined therapies [ 11 , 12 ]. Despite reasonable success, extensive and prolonged treatment often results in the development of BC resistance [ 3 ], accompanied by systemic toxicity [ 13 ].…”

A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01)

“…In fact, 3-8% and 3% of patients experienced leukopenia and thrombocytopenia, respectively, and nausea, vomiting and mucositis were also a problem. All these events occurred in a consolidation combination chemotherapy trial (Cocconi et al, 1999). Especially, in our opinion, patients of maintenance trials were linked to long-lasting intravenous therapy, while our sequential regimen was stopped after 5-6 months.…”

Paclitaxel and Epirubicin Followed by Cyclophosphamide, Methotrexate and 5-Fluorouracil for Patients With Stage IIIC Breast Cancer With Ten or More Involved Axillary Lymph Nodes

“…According to these data the administration of different chemotherapies together with a sequential intensification regimen seems a good strategy to maximize cytoreduction and avoid the acquisition of resistance. 15 A similar regimen containing sequential cisplatin/anthracycline was tested as adjuvant chemotherapy in breast cancer with more than 10 metastatic axillary nodes; compared with CMF schedule, the experimental sequential chemotherapy showed a better disease free survival. 25 In conclusion, the combination of epirubicin and lowdose paclitaxel followed by CMF is a well tolerated and feasible regimen in the adjuvant treatment of early breast cancer.…”

“…14 Furthermore, some data documented a potential therapeutic advantage in administering different sequential chemotherapy agents, changing each at the time of maximum results without waiting for a progression. 15 In view of this evidence a sequential approach could be of more benefit than concomitant polychemotherapy.…”