The effectiveness and cardiac safety of CMF plus trastuzumab in HER2-positive metastatic breast cancer

This study investigated the safety and effectiveness of treatment with combination cyclophosphamide (Cytoxan), methotrexate (Otrexup) and 5-fluoruoracil (Efudex) (CMF) plus trastuzumab (Herceptin) in HER2-positive metastatic breast cancer (MBC, cancer that has spread beyond the breast) patients. CMF plus trastuzumab (CMF+T) was found to be effective for this patient group.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast cancer. Trastuzumab treatment in combination or alone is currently recommended for treatment of HER2-positive MBC. This treatment can increase the risk of cardiac (heart issues). CMF was one of the first effective chemotherapy regimens available. The effectiveness and cardiac safety of CMF+T is not yet clear.

This study involved 90 patients with HER2-positive MBC. Patients were randomly assigned to one of two groups: one receiving 8 cycles of CMF alone and the other receiving CMF+T. Average follow up time was 44 months.

Cardiac safety was measured using LVEF, a measure of how much blood is pumped by the heart with each beat. The level of HER2-ECD-shed antigen (a protein that may be used to detect disease progression) in the blood was measured in 45 patients.

50% of patients treated with CMF+T and 32% of those treated with CMF alone responded to treatment. The average time to disease progression was 9.4 months for the CMF+T group compared to 4.8 months in the CMF alone group. The average time between treatment and death from any cause was 24.5 months for the CMF+T group compared to 19.25 months for the CMF alone group.

18% of patients in the CMF+T group experienced a decrease in LVEF drop, indicating risk of a cardiac event. 

A change in baseline HER2-ECD-shed antigen of more than 30% was associated with an increased risk of progression.  95% of these patients progressed within 3 months, and 100% within 6 months.

The study concluded that CMF+T is a safe, effective treatment option for HER2-positive patients with metastatic BC, particularly where other options are not recommended. HER2-ECD-shed antigen may be a useful method for monitoring the likelihood of disease progression.

The study was small and was originally designed for a different purpose which was altered partway through the duration. A larger, specifically designed study is needed to confirm these results.

Discuss with your doctor which treatment regimen is best for you.