Does the chemotherapy dose schedule matter for early breast cancer treatment?

This study compared the safety and efficacy of three chemotherapy regimens in early breast cancer.

Adjuvant chemotherapy, delivered following surgical removal of the tumor, reduces mortality rates in breast cancer. Recent studies have shown that dose-density chemotherapy (which increases the intensity of the therapy by shortening the time between dose cycles) and sequential chemotherapy (which delivers chemotherapy agents one at a time rather than all at once) can improve disease-free survival times compared to conventional chemotherapy regimens.

The addition of taxanes, chemotherapy agents such as paclitaxel (Taxol) and docetaxel (Taxotere), also improve chemotherapy outcomes, as does the addition of trastuzumab (Herceptin) for patients with tumors dependent on the human epidermal growth factor receptor 2 for growth. However, the optimum chemotherapy dose administration schedule has not been determined. The current study compared three chemotherapy regimens to determine which offered the most benefit for disease-free survival and overall survival with the least negative side effects in early breast cancer.

885 patients were randomized into three different chemotherapy regimens: 306 patients in Group A received the agent epirubicin (Ellence), followed by paclitaxel, then a combination of cyclophosphamide (Endoxan), methotrexate (Trexall), and fluorouracil (Efudex). 279 patients in Group B received a different order of agents: epirubicin, followed by cyclophosphamide, methotrexate, and fluorouracil, followed after a three-week break in treatment by docetaxel. 300 patients in Group C received the same schedule as Group B, but paclitaxel was delivered instead of docetaxel.

Granulocyte-colony stimulating factors were used in all patients to increase white blood cell production, which can increase immunity and decrease the risk of infection common to chemotherapy. Trastuzumab was used in addition to the chemotherapy regimens in patients with tumors dependent on the human epidermal growth factor receptor 2 for growth, and patients with tumors dependent on estrogen for growth received tamoxifen (Soltamox) to block estrogen. Patients were followed for 5 years.

There were no significant differences between the regimens in 3-year disease-free survival: 86.1% of patients in Group A were in remission at 3 years following treatment, 90.3% of Group B patients and 88.3% of Group C patients. There were no significant differences in 3-year overall survival: 95.8% of patients were alive 3 years following treatment, 96.3% of Group B patients and 95.7% of Group C patients.

Neutropenia and leukopenia, or a low white blood cell counts, occurred in 40.4% of patients, while febrile neutropenia, a fever and infection due to low white blood cells, occurred in 5.3%. Group A reported more joint/muscle pain and neurological complications, while Group B reported more skin reactions.

This study suggested that each chemotherapy regimen was of equal benefit for early breast cancer patients.