Physicians should attempt to maintain full doses of chemotherapy, especially early in the treatment course, for intermediate or high risk breast cancer patients, according to new research published in the August 2019 issue of JNCCN—Journal of the National Comprehensive Cancer Network. The study, which looked at the impact of dose reduction with the adjuvant (post-surgery) chemotherapy combination of 5-fluorouracil, epirubicin, cyclophosphamide, and docetaxel (FEC-D), found early dose reductions negatively impacted survival rates. However, outcomes were not seemingly compromised for dose reductions that came later in the treatment course.
"What surprised us the most was how dramatically early reductions in chemotherapy affect survival compared to later modifications," said Zachary Veitch, MSc, MD, FRCPC, Department of Oncology, University of Calgary, Tom Baker Cancer Centre. "This became even more apparent when patients were further separated based on chemotherapy dose cut-offs. 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."
John Ward, MD, Huntsman Cancer Institute at the University of Utah, and Member, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Breast Cancer, who was not part of the research team, agreed. "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."
The study focused on data from 1,302 women with stage I-III, HER2-negative breast cancer, who were treated with adjuvant FEC-D chemotherapy between 2007 and 2014. That data came from the Alberta Cancer Registry (ACR) in Alberta, Canada. 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 zero percent assigned for any missed cycles.
The researchers determined that 16% of the patients received less than 85% of the total recommended dose; and that the 'lower-dose' group had inferior five-year disease-free survival (79.2% vs 85.9%) and inferior overall survival (80.7% vs 88.8%) compared with those who received higher cumulative doses. However, when they split the 'lower-dose' group into 2 cohorts based on dose reduction during cycles one-to-three versus cycles four-to-six, they found that outcomes were not compromised when dose reduction occurred only during the later cycles (which are 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."
To read the entire study and view the corresponding data tables, visit JNCCN.org. Complimentary access to "Impact of Cumulative Chemotherapy Dose on Survival with Adjuvant FEC-D Chemotherapy for Breast Cancer" is available until November 10, 2019.
About JNCCN—Journal of the National Comprehensive Cancer Network
More than 25,000 oncologists and other cancer care professionals across the United States read JNCCN—Journal of the National Comprehensive Cancer Network. This peer-reviewed, indexed medical journal provides the latest information about best clinical practices, health services research, and translational medicine. JNCCN features updates on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), review articles elaborating on guidelines recommendations, health services research, and case reports highlighting molecular insights in patient care. JNCCN is published by Harborside. Visit JNCCN.org. To inquire if you are eligible for a FREE subscription to JNCCN, visit http://www.nccn.org/jnccn/subscribe.asp. Follow JNCCN on Twitter @JNCCN.
John Ward, MD, Huntsman Cancer Institute at the University of Utah, and Member, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Breast Cancer, who was not part of the research team, agreed. "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."
The study focused on data from 1,302 women with stage I-III, HER2-negative breast cancer, who were treated with adjuvant FEC-D chemotherapy between 2007 and 2014. That data came from the Alberta Cancer Registry (ACR) in Alberta, Canada. 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 zero percent assigned for any missed cycles.
The researchers determined that 16% of the patients received less than 85% of the total recommended dose; and that the 'lower-dose' group had inferior five-year disease-free survival (79.2% vs 85.9%) and inferior overall survival (80.7% vs 88.8%) compared with those who received higher cumulative doses. However, when they split the 'lower-dose' group into 2 cohorts based on dose reduction during cycles one-to-three versus cycles four-to-six, they found that outcomes were not compromised when dose reduction occurred only during the later cycles (which are 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."
To read the entire study and view the corresponding data tables, visit JNCCN.org. Complimentary access to "Impact of Cumulative Chemotherapy Dose on Survival with Adjuvant FEC-D Chemotherapy for Breast Cancer" is available until November 10, 2019.
About JNCCN—Journal of the National Comprehensive Cancer Network
More than 25,000 oncologists and other cancer care professionals across the United States read JNCCN—Journal of the National Comprehensive Cancer Network. This peer-reviewed, indexed medical journal provides the latest information about best clinical practices, health services research, and translational medicine. JNCCN features updates on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), review articles elaborating on guidelines recommendations, health services research, and case reports highlighting molecular insights in patient care. JNCCN is published by Harborside. Visit JNCCN.org. To inquire if you are eligible for a FREE subscription to JNCCN, visit http://www.nccn.org/jnccn/subscribe.asp. Follow JNCCN on Twitter @JNCCN.
