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Total Cumulative Chemotherapy Dose and Survival in Breast Cancer

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Key Points

  • The group who had received the lower dose had inferior 5-year disease-free survival (79.2% vs 85.9%) and inferior overall survival (80.7% vs 88.8%) compared with patients who received higher cumulative doses.
  • When researchers split the lower-dose group into two cohorts based on dose reduction during cycles 1 to 3 vs cycles 4 to 6, they found that outcomes were not compromised when dose reduction occurred only during the later cycles (which were the only cycles to include docetaxel).

Physicians should attempt to maintain full doses of chemotherapy, especially early in the course of treatment, for patients with intermediate- or high-risk breast cancer, according to research published by Veitch et al in JNCCN—Journal of the National Comprehensive Cancer NetworkThe study, which looked at the impact of dose reduction of the adjuvant combination of fluorouracil, epirubicin, cyclophosphamide, and docetaxel (FEC-D), found early dose reductions negatively impacted survival rates. However, outcomes were not compromised by dose reductions that came later in the course of treatment.

“What surprised us the most was how dramatically early reductions in chemotherapy affect[ed] survival compared to later modifications,” said Zachary Veitch, MSc, MD, FRCPC, of the Department of Oncology, University of Calgary, and Tom Baker Cancer Centre. “This became even more apparent when patients were further separated based on chemotherapy dose cutoffs. Early dose reductions can be related to age, weight, or the number of other medical issues a patient has, such as kidney disease or diabetes, among other factors. Often, the first cycle of chemotherapy can be difficult for patients, and oncologists must convey the need for maintaining initial dose intensity while using other medications to control side effects and manage comorbidities.”

The study focused on data from the Alberta Cancer Registry on 1,302 women with stage I to III, HER2-negative breast cancer who were treated with adjuvant FEC-D between 2007 and 2014. Patients received at least four cycles of FEC-D but no more than six. The total dose was averaged across the treatments, with a value of 0% assigned for any missed cycles.

Study Results

The researchers determined that 16% of the patients received less than 85% of the total recommended dose. They found that the group receiving the lower dose had inferior 5-year disease-free survival (79.2% vs 85.9%) and inferior overall survival (80.7% vs 88.8%) compared with patients who received higher cumulative doses. However, when researchers split the lower-dose group into two cohorts based on dose reduction during cycles 1 to 3 vs cycles 4 to 6, they found that outcomes were not compromised when dose reduction occurred only during the later cycles (which were the only cycles to include docetaxel).

“There may be a few reasons for this,” speculated Dr. Veitch. “First, the amount of docetaxel that was prescribed in the last three cycles may be higher than needed for the FEC-D regimen. Lower doses have been shown to be as effective in other standard-of-care chemotherapy regimens, and lower doses have been used in other countries with good outcomes. Second, the majority of cancer cells that are sensitive to chemotherapy may be killed in the first few treatments, rather than in the later treatments. Thus, reducing the dose late may not have as much of an impact.”

The researchers concluded, “Chemotherapy total cumulative dose < 85% for adjuvant FEC-D affects breast cancer survival. Late reductions (docetaxel only) were not shown to adversely affect disease-free survival or overall survival. Conversely, early reductions (FEC±D) negatively affected patient outcomes.”

John Ward, MD, of the Huntsman Cancer Institute at the University of Utah, and Member of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Breast Cancer, who was not involved in the study, said, “Adjuvant therapy in early-stage breast cancer leads to improved survival. When chemotherapy is part of the adjuvant treatment, it is important to give the prescribed doses. This study adds further support for the need to do so. Balancing side effects with efficacy is always a challenge. When a treatment is palliative, quality of life factors into dosing choices. When cure is the goal, as it is with adjuvant therapy, it is important to strive to give the therapy as planned. The juice is worth the squeeze.”

Disclosures: For full disclosures of the study authors, visit jnccn.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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