NEW YORK (Reuters Health) Jul 21 - In postmenopausal women with node-positive early breast cancer, substituting docetaxel for epirubicin for the last three cycles of chemotherapy may improve outcome without adversely affecting quality of life, a small study suggests.
"Previously, many clinicians felt that this strategy would likely adversely affect patients' quality of life but here we find that Taxotere does not lower quality of life," study investigator Dr. Charles Coombes, of the Division of Cancer, Imperial College London, United Kingdom, told Reuters Health.
"In fact, our results indicate that cardiac adverse events occur more often in patients who continue with the cardiotoxic anthracycline rather than switching to Taxotere," he wrote in an email.
The Docetaxel Epirubicin Adjuvant (DEVA) trial compared single-agent anthracycline chemotherapy with a sequential anthracycline-taxane regimen in 803 postmenopausal women with node-positive early breast cancer.
After complete tumor excision, patients were randomized to six cycles of epirubicin 50 mg/m2 on days 1 and 8 every 4 weeks (EPI X 6; n = 397) or to three cycles of epirubicin 50 mg/m2 on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m2 on day 1 every 3 weeks (EPI-DOC; n = 406). Some of the women in the study received concurrent or sequential tamoxifen.
The primary end point was disease-free survival (DFS) and quality of life was assessed in a subset of subjects.
In the Journal of Clinical Oncology published online July 18, the study team reports that at a median follow-up of 64.7 months, a total of 198 DFS events (mostly distant relapse) were reported, with a greater number in the EPI X 6 arm than the EPI-DOC arm (114 vs. 84).
An improvement in DFS was seen for EPI-DOC compared with EPI X 6, with an unadjusted hazard ratio (HR) of 0.68 (p=0.008), they report.
In the intention-to-treat population, the 5-year DFS rates were 72.7% with EPI X 6 and 79.5% with EPI-DOC, which translates into a 5-year absolute improvement in DFS of 6.8% with EPI-DOC. After adjustment for known prognostic factors, the HR was 0.58 (p<0.001).
Over a median follow-up of about 5 years, 127 patients died (75 in the EPI X 6 arm, and 52 in the EPI-DOC arm); 107 of these deaths were due to breast cancer (62 in the EPI X 6 arm and 45 in the EPI-DOC arm).
"There was a statistically significant improvement in overall survival in favor of EPI-DOC" (HR, 0.66; p=0.02), the study team reports.
At 5-years, the overall survival rates were 81.8% with EPI X 6 vs. 88.9% with EPI-DOC.
The improvement in overall survival for patients who switch to docetaxel "comes at a cost in terms of adverse effects," the investigators report, including a higher incidence of febrile neutropenia, skin disorders, stomatitis, diarrhea and other chemotherapy-related toxicities.
However, this didn't appear to reduce quality of life during follow-up, they say.
"The principal message is that older postmenopausal patients with breast cancer should be given sequential Taxotere after anthracyclines if they have a significant chance of relapse, since by doing this we can increase the cure rate," Dr. Coombes said.
The study was supported by Pfizer and Sanofi, and six of the researchers report financial ties to one or both of those companies.
"Previously, many clinicians felt that this strategy would likely adversely affect patients' quality of life but here we find that Taxotere does not lower quality of life," study investigator Dr. Charles Coombes, of the Division of Cancer, Imperial College London, United Kingdom, told Reuters Health.
"In fact, our results indicate that cardiac adverse events occur more often in patients who continue with the cardiotoxic anthracycline rather than switching to Taxotere," he wrote in an email.
The Docetaxel Epirubicin Adjuvant (DEVA) trial compared single-agent anthracycline chemotherapy with a sequential anthracycline-taxane regimen in 803 postmenopausal women with node-positive early breast cancer.
After complete tumor excision, patients were randomized to six cycles of epirubicin 50 mg/m2 on days 1 and 8 every 4 weeks (EPI X 6; n = 397) or to three cycles of epirubicin 50 mg/m2 on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m2 on day 1 every 3 weeks (EPI-DOC; n = 406). Some of the women in the study received concurrent or sequential tamoxifen.
The primary end point was disease-free survival (DFS) and quality of life was assessed in a subset of subjects.
In the Journal of Clinical Oncology published online July 18, the study team reports that at a median follow-up of 64.7 months, a total of 198 DFS events (mostly distant relapse) were reported, with a greater number in the EPI X 6 arm than the EPI-DOC arm (114 vs. 84).
An improvement in DFS was seen for EPI-DOC compared with EPI X 6, with an unadjusted hazard ratio (HR) of 0.68 (p=0.008), they report.
In the intention-to-treat population, the 5-year DFS rates were 72.7% with EPI X 6 and 79.5% with EPI-DOC, which translates into a 5-year absolute improvement in DFS of 6.8% with EPI-DOC. After adjustment for known prognostic factors, the HR was 0.58 (p<0.001).
Over a median follow-up of about 5 years, 127 patients died (75 in the EPI X 6 arm, and 52 in the EPI-DOC arm); 107 of these deaths were due to breast cancer (62 in the EPI X 6 arm and 45 in the EPI-DOC arm).
"There was a statistically significant improvement in overall survival in favor of EPI-DOC" (HR, 0.66; p=0.02), the study team reports.
At 5-years, the overall survival rates were 81.8% with EPI X 6 vs. 88.9% with EPI-DOC.
The improvement in overall survival for patients who switch to docetaxel "comes at a cost in terms of adverse effects," the investigators report, including a higher incidence of febrile neutropenia, skin disorders, stomatitis, diarrhea and other chemotherapy-related toxicities.
However, this didn't appear to reduce quality of life during follow-up, they say.
"The principal message is that older postmenopausal patients with breast cancer should be given sequential Taxotere after anthracyclines if they have a significant chance of relapse, since by doing this we can increase the cure rate," Dr. Coombes said.
The study was supported by Pfizer and Sanofi, and six of the researchers report financial ties to one or both of those companies.
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