In the Journals

Early reductions in adjuvant chemotherapy dose may impact breast cancer survival

Early adjuvant chemotherapy dose reductions appeared to adversely affect survival outcomes among women with intermediate- or high-risk breast cancer, according to results of a retrospective study published in Journal of the National Comprehensive Cancer Network.

However, later dose reductions of the adjuvant regimen — which consisted of 5-FU, epirubin, cyclophosphamide and docetaxel (FEC-D) — did not impact these outcomes, researchers noted.

“What surprised us the most was how dramatically early reductions in chemotherapy affect survival compared with later modifications,” Zachary Veitch, MSc, MD, FRCPC, clinical oncologist in the department of oncology at Tom Baker Cancer Centre at University of Calgary, said in a press release. “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.”

Previous studies have shown that reductions to less than 85% of the total recommended adjuvant chemotherapy dose for historical regimens negatively affect breast cancer survival. However, this threshold remained unclear for third-generation anthracycline/taxane-based chemotherapy.

Veitch and colleagues retrospectively analyzed the effect of chemotherapy total cumulative dose and early vs. late dose reductions among 1,302 women with stage I to stage III, hormone receptor-positive or -negative, HER2-negative breast cancer who received adjuvant FEC-D chemotherapy. Women received at least four but no more than six cycles of chemotherapy.

Overall, 16% of the women had their treatment dose reduced below 85%.

Women who received a higher dose appeared more likely to be younger (median age, 54 vs. 57 years; P < .001) and premenopausal (44.5% vs. 28.2%; P .001) and have fewer comorbidities.

DFS and OS served as the study’s primary endpoint.

Results showed that women who did not have their treatment dose reduced below 85% had superior 5-year DFS (85.9% vs. 79.2%; P = .025) and 5-year OS (88.8% vs. 80.7%; P < .001) compared with women who had their treatment dose reduced.

When researchers divided the lower-dose group into two cohorts based on the timing of the dose reduction, they observed negative survival trends for early vs. late reductions in dose (HR for DFS = 1.46; HR for OS = 1.77). Outcomes did not appear to be compromised when dose reduction occurred in the later cycles.

“There may be a few reasons for this,” Veitch said. “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.”

Granulocyte-colony stimulating factor administration and number of cycles were not recorded, which served as the study’s primary limitation.

“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,” John Ward, MD, clinical oncologist at Huntsman Cancer Institute at University of Utah and member of the National Comprehensive Cancer Network Guidelines panel for breast cancer, who was not on the research team, said in a press release. “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.” – by John DeRosier

Disclosures: Veitch reports no relevant financial disclosures. One study author reports consulting fees/honoraria from Amgen, Apobiologix and Sandoz. HemOnc Today could not confirm Ward’s relevant financial disclosures at the time of reporting.

Early adjuvant chemotherapy dose reductions appeared to adversely affect survival outcomes among women with intermediate- or high-risk breast cancer, according to results of a retrospective study published in Journal of the National Comprehensive Cancer Network.

However, later dose reductions of the adjuvant regimen — which consisted of 5-FU, epirubin, cyclophosphamide and docetaxel (FEC-D) — did not impact these outcomes, researchers noted.

“What surprised us the most was how dramatically early reductions in chemotherapy affect survival compared with later modifications,” Zachary Veitch, MSc, MD, FRCPC, clinical oncologist in the department of oncology at Tom Baker Cancer Centre at University of Calgary, said in a press release. “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.”

Previous studies have shown that reductions to less than 85% of the total recommended adjuvant chemotherapy dose for historical regimens negatively affect breast cancer survival. However, this threshold remained unclear for third-generation anthracycline/taxane-based chemotherapy.

Veitch and colleagues retrospectively analyzed the effect of chemotherapy total cumulative dose and early vs. late dose reductions among 1,302 women with stage I to stage III, hormone receptor-positive or -negative, HER2-negative breast cancer who received adjuvant FEC-D chemotherapy. Women received at least four but no more than six cycles of chemotherapy.

Overall, 16% of the women had their treatment dose reduced below 85%.

Women who received a higher dose appeared more likely to be younger (median age, 54 vs. 57 years; P < .001) and premenopausal (44.5% vs. 28.2%; P .001) and have fewer comorbidities.

DFS and OS served as the study’s primary endpoint.

Results showed that women who did not have their treatment dose reduced below 85% had superior 5-year DFS (85.9% vs. 79.2%; P = .025) and 5-year OS (88.8% vs. 80.7%; P < .001) compared with women who had their treatment dose reduced.

When researchers divided the lower-dose group into two cohorts based on the timing of the dose reduction, they observed negative survival trends for early vs. late reductions in dose (HR for DFS = 1.46; HR for OS = 1.77). Outcomes did not appear to be compromised when dose reduction occurred in the later cycles.

“There may be a few reasons for this,” Veitch said. “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.”

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Granulocyte-colony stimulating factor administration and number of cycles were not recorded, which served as the study’s primary limitation.

“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,” John Ward, MD, clinical oncologist at Huntsman Cancer Institute at University of Utah and member of the National Comprehensive Cancer Network Guidelines panel for breast cancer, who was not on the research team, said in a press release. “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.” – by John DeRosier

Disclosures: Veitch reports no relevant financial disclosures. One study author reports consulting fees/honoraria from Amgen, Apobiologix and Sandoz. HemOnc Today could not confirm Ward’s relevant financial disclosures at the time of reporting.