Intense Dose-Dense Sequential Chemotherapy With Epirubicin, Paclitaxel, and Cyclophosphamide Compared With Conventionally Scheduled Chemotherapy in High-Risk Primary Breast Cancer: Mature Results of an AGO Phase III Study

2010 ◽  
Vol 28 (17) ◽  
pp. 2874-2880 ◽  
Author(s):  
Volker Moebus ◽  
Christian Jackisch ◽  
Hans-Joachim Lueck ◽  
Andreas du Bois ◽  
Christoph Thomssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Primary Breast Cancer ◽  
Survival Rates ◽  
Phase Iii ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Event Free Survival ◽  
Free Survival ◽  
Dose Dense

Purpose Patients with primary breast cancer who have extensive axillary lymph node involvement have a poor prognosis after conventional adjuvant therapy. We compared intense dose-dense (IDD) adjuvant chemotherapy with conventionally scheduled adjuvant chemotherapy in patients with high-risk primary breast cancer. Patients and Methods In this randomized, phase III trial, a total of 1,284 eligible patients with four or more involved axillary lymph nodes were randomly assigned to receive IDD sequential epirubicin, paclitaxel, and cyclophosphamide (IDD-ETC) every 2 weeks or conventionally scheduled epirubicin/cyclophosphamide followed by paclitaxel every three weeks. The primary end point was event-free survival (EFS). Results At a median follow-up of 62 months, 5-year event-free survival rates were 62% in the conventional arm and 70% in the IDD-ETC arm, representing a 28% reduction of the relative risk of relapse (P < .001). This benefit was independent of menopausal, hormone receptor, or human epidermal growth factor receptor 2 status. The 5-year overall survival rates were 77% versus 82%, representing a 24% reduction of the relative risk of death (P = .0285). IDD therapy was associated with significantly more nonhematologic and hematologic toxicities, but no treatment-related death occurred. Four occurrences of acute myeloid leukemia or myelodysplastic syndrome (MDS) were observed in the IDD-ETC arm. No severe congestive heart failure was reported. Conclusion IDD-ETC was less well tolerated compared with conventional chemotherapy but significantly improved event-free and overall survivals in patients with high-risk primary breast cancer who had four or more positive axillary lymph nodes.

Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11566-e11566
Author(s):  
S. Koya ◽  
Y. Li ◽  
S. A. McDaniel ◽  
A. F. LoBuglio ◽  
H. Krontiras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Lymph Nodes ◽  
Triple Negative ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
Dose Dense

e11566 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy (AC) either pre- or postoperatively; in the study there was no significant difference in disease free survival (DFS) or overall survival (OS) among patients in either group. Pathologic complete response rate (pCR) was directly proportional to DFS and OS. Dose dense adjuvant chemotherapy (ATC) has shown a statistically significant improvement in DFS and OS. Methods: We performed a single institution review of pts enrolled in a neoadjuvant trial and who received dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2wks x4, paclitaxel 175 mg/m2 IV Q2wks x4, and cyclophosphamide 600 mg/m2 IV Q2wks x4) to assess response rates, safety, and DFS. Women with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were enrolled. Results: Since 02/2003, 43 pts were enrolled (mean age 47.6, range 28–64) and received dose dense chemotherapy. 41.4% of the pts were triple negative and 14.6% were Her2+ by FISH or IHC. The median follow-up is 49 months (range 8–69). Two patients dropped out without finishing therapy. Forty one pts completed dose dense chemotherapy and proceeded to surgery. 17 pts (41.4%) achieved a pCR in the breast and of those 14 pts were also negative in the axillary lymph nodes (34.1% pCR in the breast and lymph nodes). 10 of the 17 pts with pCR in the breast (8 out of the 14 pts with pCR in breast and axillary lymph nodes) were triple negative. 18 pts (43.9%) achieved PR, 3 pts (7.31%) had SD and 3 pts (7.31%) had PD. Up to November 2008, 7 pts who did not have a pCR have relapsed (4 triple negative, 1 Her2+, 1 ER/PR positive and 1 ER negative, PR positive) with a relapsed free survival rate of 85%. Hematologic toxicity consisted of grade 3 anemia in 2 patients with no grade 4 anemia, no G4 thrombocytopenia and febrile neutropenia in 2 pts. Non-hematologic grade 3 or 4 toxicity consisted of mediport thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and varicella zoster in 1 pt. Conclusions: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast + node) in about 1/3 of patients (34%) with tolerable toxicity; although the number of patients is limited, our data suggest that triple negative breast cancer seems to be the most sensitive tumor to this regimen. No significant financial relationships to disclose.

Intensive Dose-Dense Compared With Conventionally Scheduled Preoperative Chemotherapy for High-Risk Primary Breast Cancer

2009 ◽  
Vol 27 (18) ◽  
pp. 2938-2945 ◽  
Author(s):  
Michael Untch ◽  
Volker Möbus ◽  
Walther Kuhn ◽  
Bernd Rudolph Muck ◽  
Christoph Thomssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Preoperative Chemotherapy ◽  
Primary Breast Cancer ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Pathologic Complete Response Rate ◽  
Dose Dense

Purpose To compare preoperative intense dose-dense (IDD) chemotherapy with conventionally scheduled preoperative chemotherapy in high-risk primary breast cancer (BC). Patients and Methods In this randomized phase III trial a total of 668 eligible primary BC patients stratified for tumors ≥ 3 cm (n = 567) or inflammatory BC (n = 101) were randomly assigned to receive concurrent preoperative epirubicin/paclitaxel every 3 weeks or dose-dense and dose-escalated sequential epirubicin followed by paclitaxel every 2 weeks. All patients received three cycles of cyclophosphamide, methotrexate, and fluorouracil chemotherapy after surgery. Results IDD treatment significantly improved pathologic complete response rate (18% v 10%; odds ratio [OR] 1.89; P = .008), disease-free survival (DFS; hazard ratio [HR], 0.71; P = .011), and overall survival (OS; HR, 0.83; P = .041) compared to epirubicin/paclitaxel. Patients with inflammatory BC had a particularly poor prognosis and did not appear to benefit from IDD therapy in this trial (DFS HR, 1.10; P = .739; OS HR, 1.25; P = .544). In contrast, patients with noninflammatory BC significantly benefited from IDD treatment (DFS HR, 0.65, P = .005; OS HR, 0.77, P = .013). Treatment effects in multivariate analysis were significant for noninflammatory BC (DFS HR, 0.65, P = .015; OS HR, 0.79, P = .034), but not for all patients (DFS HR, 0.76; P = .088; OS HR, 0.82; P = .059). IDD therapy was associated with significantly more nonhematologic toxicities, anemia, and thrombocytopenia, but with similar neutropenia and infection rates. Conclusion Our results support the efficacy and short-term safety of IDD as preoperative chemotherapy. IDD was less well tolerated compared to standard treatment, but improved clinical outcomes in patients with noninflammatory high-risk primary BC.

Adjuvant aminoglutethimide for postmenopausal patients with primary breast cancer: analysis at 8 years.

1992 ◽  
Vol 10 (10) ◽  
pp. 1547-1552 ◽  
Author(s):  
A L Jones ◽  
T J Powles ◽  
M Law ◽  
A Tidy ◽  
D Easton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Controlled Trial ◽  
Multicenter Trial ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Event Free Survival ◽  
Double Blind ◽  
Free Survival

PURPOSE The study purpose was to evaluate aminoglutethimide (AG) as adjuvant therapy in patients with primary node-positive breast cancer in a randomized double-blind placebo-controlled trial. PATIENTS AND METHODS In a multicenter trial, 354 postmenopausal women with early breast cancer and histologically confirmed positive axillary lymph nodes were randomized after surgery to received aminoplac. Patients were prescribed either AG 250 mg four times per day and hydrocortisone 20 mg twice per day or placebos of identical appearance for 2 years. RESULTS After a median follow-up of 8.1 years, there has been no overall benefit for AG in terms of either event-free survival or overall survival (OS). However, the results are consistent with interim analyses with a significantly improved event-free survival for patients who received AG for up to 4 years, although this benefit subsequently disappears. Similarly, there is an improved OS for patients who received AG for up to 4 years, but this also subsequently disappears. There was a marginal advantage for estrogen receptor (ER)-positive patients who received AG (n = 74; P = .054). There was no difference in the sites of relapse. There was a significant increase in toxicity for patients who received AG. CONCLUSION The lack of survival benefit with long-term follow-up for AG may indicate that aromatase inhibitors have less of an impact on early breast cancer than tamoxifen and may imply different biologic mechanisms of action.

A phase III adjuvant trial of sequenced EC + filgrastim + epoetin-alpha followed by paclitaxel compared to sequenced AC followed by paclitaxel compared to CEF in women with node-positive or high-risk node-negative breast cancer (NCIC CTG MA.21)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 550-550 ◽  
Author(s):  
M. J. Burnell ◽  
M. N. Levine ◽  
J. A. Chapman ◽  
V. Bramwell ◽  
T. Vandenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Free Survival ◽  
Node Negative ◽  
Node Positive ◽  
Node Negative Breast Cancer ◽  
Dose Dense

550 Background: CEF and AC followed by paclitaxel (AC/T) are commonly used adjuvant regimens in women with early breast cancer. In a trial conducted by the EORTC, NCIC CTG, and SAKK three months of dose-dense EC was equivalent to six months of CEF in women with locally advanced breast cancer. We hypothesized that three months of a taxane following dose-dense EC would be superior to CEF alone or AC/T. The results of a planned interim analysis were presented in San Antonio 2006 (Abstract #53). We now present more detailed results on efficacy and toxicity. Methods: Women 60 years of age or younger, with axillary node positive or high risk node negative breast cancer were randomized to CEF, EC/T or AC/T for six months. Results: Between December 2000 and April 2005, 2104 patients were enrolled. The median follow-up is 30.4 months. Hazard ratios for recurrence are: AC/T vs. CEF, 1.49 (95% CI, 1.12–1.99), p=0.005; AC/T vs. EC/T, 1.68 (95% CI, 1.25–2.27), p=0.0006; and EC/T vs. CEF, 0.89 (95% CI, 0.64–1.22), p=0.46. Three year recurrence-free survival rates for CEF, EC/T, and AC/T are 90.1, 89.5 and 85.0%, respectively. There was no significant interaction between ER status and treatment. Multivariate analysis of predictive factors will be presented. The numbers of deaths are 50 (CEF), 47 (EC/T) and 65 (AC/T). There was more toxicity in CEF and EC/T compared to AC/T. Conclusion: AC/T given every three weeks, although less toxic is significantly inferior to CEF or EC/T in terms of relapse-free survival. It is too early to detect any difference between CEF and dose-dense EC/T. Our results indicate that there is still room to explore anthracycline and taxane adjuvant chemotherapy regimens. Supported by: NCI Canada and Canadian Cancer Society, Pfizer, Bristol-Myers Squibb, Amgen, Janssen Ortho, Ortho Biotech, and NCI US. [Table: see text] No significant financial relationships to disclose.

scholarly journals Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients

Breast Care ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. 159-164
Author(s):  
Mattea Reinisch ◽  
Oleg Gluz ◽  
Beyhan Ataseven ◽  
Jens-Uwe Blohmer ◽  
Marek Budner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Phase Iii ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Dose Dense

Purpose: Although dose-dense (dd) chemotherapy plays a fundamental role in the treatment of breast cancer (BC), a variety of trials have presented divergent survival results. Here, we present data of patients with more than 3 positive axillary lymph nodes (+aLN) receiving dd chemotherapy after a median follow-up period of 12.3 years. Methods: In the years 1996-2000, 231 patients with invasive BC, ≥pN2a and no evidence of distant metastases were recruited to receive treatment A, i.e. dd 3 × epirubicin (E, 90 mg/m2) + paclitaxel (P, 175 mg/m2) every 2 weeks (q2w) followed by 3 × cyclophosphamide (C)/methotrexate/5-fluorouracil (CMF, 600/40/600 mg/m2, q2w), or treatment B, i.e. 4 × E + C (C, 600 mg/m2) q3w followed by 3 × CMF q3w. Results: 113 patients in arm A and 113 patients in arm B were analysed after an updated median follow-up of 12.3 years. The median age was 55 years, with a median number of 6 +aLN, 50.4% had a T2 and 79.2% hormone receptor-positive BC. The disease-free survival (DFS) rate was 53.1% in arm A and 42.5% in arm B (adjusted p = 0.027). The overall survival (OS) rate was 54.9% in arm A and 48.7% in arm B (adjusted p = 0.058). In the multivariable analysis, the tumour burden was a significant predictor for DFS and OS. Conclusion: The adjuvant use of dd chemotherapy led to a statistically significant improvement of DFS after a follow-up of 12.3 years.

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