scholarly journals Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

2013 ◽  
Vol 31 (26) ◽  
pp. 3197-3204 ◽  
Author(s):  
Sandra M. Swain ◽  
Gong Tang ◽  
Charles E. Geyer ◽  
Priya Rastogi ◽  
James N. Atkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Node Positive ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

Purpose Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. Results There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Conclusion Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

Neoadjuvant dose-dense docetaxel, carboplatinum, and trastuzumab (ddTCH) chemotherapy for HER2 overexpressing breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11557-e11557 ◽  
Author(s):  
S. Bayraktar ◽  
U. D. Bayraktar ◽  
I. M. Reis ◽  
M. Pegram ◽  
C. Welsh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
High Risk Group ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

e11557 Background: Neoadjuvant chemotherapy for locally advanced breast cancer was shown to improve the complete pathologic (pCR) and clinical response (cCR) as well as the disease free survival (DFS). Docetaxel, cisplatin, and trastuzumab given every 21 days in her2-positive breast cancer demonstrated a pCR rate of 23%. The concept of dose dense chemotherapy regimens has attracted much attention and we hypothesized that dose-dense regimen would further improve pCR, cCR and would maintain the safety profile while being a suitable regimen for outpatient administration. Methods: 48 patients with stage II/III HER2-positive breast cancer were prospectively enrolled on a clinical trial of a neoadjuvant regimen consisting of docetaxel 70 mg/m2 on days 1, 15, 29, and 43; carboplatinum at an AUC of 6 on days 1, 15, 29, and 43; trastuzumab 4 mg/kg on day 1 and 2 mg/kg weekly x 10 starting on day 8; peg-filgastrim 6 mg on days 2, 16, 30, and 44. Results: The median age was 50 years (range 30–78). 52% of patients were premenopausal, 63% and 22% were of Hispanic and African descent, respectively. Estrogen receptor was positive in 52% patients and median tumor size was 5 cm at the time of diagnosis. TNM stage distribution at presentation: T1 2%, T2 25%, T3 57%, T4 16%; N0 29%, N1 46%, N2 16%, N3 7%; M0 100%. pCR in breast; axilla; and both breast and axilla was observed in 19 of 44 patients (43.2%; 95% CI 28.3% - 59.0%); in 29 of 44 patients (65.9%; 95% CI 50.1% - 79.5%); and in 16 of 44 patients (36.4%; 95% CI 22.4% - 52.2%), respectively. No grade 4 or 5 toxicity occurred. The most frequent grade 3 toxicities were hand-foot syndrome (7%), neutropenia (4%), nausea/vomiting (2%), and bone pain (2%). Grade 2 cardiotoxicity was seen in 8% of patients and no grade 3 cardiotoxicity was observed. Conclusions: This neoadjuvant regimen was well tolerated and yielded a good pCR rate for this high risk group of patients. No significant financial relationships to disclose.

scholarly journals Dose-Dense Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel in Node-Positive Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Hamid Reza Mirzaei ◽  
Fatemeh Nasrollahi ◽  
Ladan Mohammadi Yeganeh ◽  
Sepideh Jafari Naeini ◽  
Pegah Bikdeli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Weekly Paclitaxel ◽  
Hematologic Toxicity ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement in node-positive breast cancer patients but the optimal dose schedule has still remained undetermined. Objectives. The feasibility of dose-dense epirubicin in combination with cyclophosphamide (EC) followed by weekly paclitaxel as adjuvant chemotherapy in node-positive breast cancer patients was investigated. Methods. All patients were treated with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) every two weeks for four cycles with daily Pegfilgrastim (G-CSF) that was administered 3–10 days after each cycle of epirubicin and cyclophosphamide infusion which followed by (80 mg/m2) paclitaxel for twelve consecutive weeks. Results. Sixty consecutive patients were analyzed, of whom 57 patients (95%) completed the regimen and no case of toxicity-related death was observed. Grade 3/4 hematologic toxicity was uncommon and the most common grade 3/4 nonhematological adverse event was neuropathy disorders. Conclusions. Dose-dense epirubicin and cyclophosphamide followed by weekly paclitaxel with G-CSF support is a well-tolerated and feasible regimen in node-positive breast cancer patients without serious complications.

Dose-dense (DD) cyclophosphamide, methotrexate, and fluorouracil (CMF) at 14-day intervals: A pilot study of every 14- and 10–11-day dosing intervals for women with early-stage breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 590-590
Author(s):  
P. Drullinsky ◽  
M. N. Fornier ◽  
S. Sugarman ◽  
G. D'Andrea ◽  
T. Troso-Sandoval ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Hematologic Toxicity ◽  
Type I ◽  
Initial Cohort ◽  
Grade 3 ◽  
Dose Dense ◽  
Q 14 ◽  
Dosing Intervals

590 Background: CMF (C 600 mg/m2, M 40 mg/m2, F 600 mg/m2) is an option for adjuvant therapy for patients with low risk early stage breast cancer. DD regimens as predicted by mathematical models of cancer growth and treatment response are superior. We previously demonstrated the safety of DD EC (epirubicin/cyclophosphamide) followed by paclitaxel at 10–11 day (d) intervals. We investigated the feasibility of administering DD adjuvant CMF every 14 d and then every 10–11 d in a 2-stage phase II trial. Methods: An initial cohort (A) was treated q 14 d with PEG-filgrastim (Neulasta) support. A second cohort (B) was treated every 10–11 d with filgrastim/Neupogen x 5 d and then, based on feasibility, modified (cohort C) to use 7 d filgrastim. The primary end point was feasibility defined as having ANC > 1.5 x 103/uL on day 1 of planned treatment for all 8 cycles with no grade 3 or higher non-hematologic toxicity. All three cohorts were tested using a Simon's two-stage optimal design with type I and type II errors set at 10%. This design would effectively discriminate between true tolerability (as protocol-defined) rates of< 60% and> 80%. Cohort A: 38 pts with early stage breast cancer were accrued from 3/2008 though 6/2008. Cohort B: 7 pts were accrued from June 2008 through August 2008. Cohort C: Is still open with 16 pts accrued from August 2008 through December 5, 2008. Results: Median age 51: range 38 to 78. Cohort A: 29/38 pts completed 8 cycles of CMF. The regimen was considered feasible. 2 other pts completed 7 cycles and were withdrawn for depression and grade 2 transaminitis. The 7 other pts completed between 1 and 6 cycles of CMF were withdrawn as follows: 3 personal, 1 (grade 3) bone pain, 2 allergy unrelated to CMF, and 1 seizure. Cohort B: 7 pts were accrued. 6 out of 7 pts could not complete 8 cycles of chemotherapy secondary to neutropenia and 1 secondary to grade 3 ALT elevation. Cohort C: Accrual has not been completed. 16 pts are currently enrolled. Conclusions: Dose dense adjuvant CMF is feasible at 14 d intervals with PEG-filgrastim support. Adjuvant CMF every 10–11 days with filgrastim given for 5 days beginning day 2 is not feasible. Accrual is ongoing for CMF at 10–11 days with filgrastim x 7 days. Updated results will be available for Cohort C. [Table: see text]

Longer follow-up on cardiac safety and distant disease free survival of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab in patients with early-stage HER2-positive breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 540-540
Author(s):  
Rui Wang ◽  
Anthony Francis Yu ◽  
Richard Steingart ◽  
Sujata Patil ◽  
Jose Baselga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Her2 Positive ◽  
Distant Disease ◽  
Free Survival ◽  
Her2 Positive Breast Cancer ◽  
Dose Dense ◽  
Positive Breast Cancer

540 Background: We previously reported the cardiac safety results and distant disease-free survival (DDFS) on a phase 2 trial of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) in patients with early stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The incidence of congestive heart failure (CHF) was 1.4% both at a median follow-up of 2 and 7 years. Here, we report updated CHF and DDFS rates with longer follow-up. Methods: Patients were enrolled with HER2 overexpressed (immunohistochemistry 3+) or amplified (fluorescent in situ hybridization ratio > 2.0) disease, regardless of size or nodal status, and baseline left ventricular ejection fraction (LVEF) of > 55%. Patients (pts) received dd AC (60/600 mg/m2) q 2 weeks (w) x 4 →T (175 mg/m2) q 2 w x 4 with H (loading dose 4 mg/kg → 2 mg/kg q w during T → 6 mg/kg q 3 w for rest of 1 year); pegfilgrastim was administered after each chemotherapy cycle. LVEF monitoring with multigated acquisition scan occurred at baseline, months 2 (after AC), 6, 9, and 18 (after therapy completion). Results: From January 2005 to November 2005, 70 pts were enrolled; 2 (3%) and 68 (97%) were treated in neoadjuvant and adjuvant settings, respectively. In 68 pts treated in adjuvant setting, 40 (60%) and 27 (40%) had node-positive and node-negative disease, respectively. The median age was 49 years old (range 27-72); 55 (79%) had hormone-receptor positive disease, 11 (16%) had hypertension, and 21 (30%) had left sided radiation. The median baseline LVEF was 68% [range, 55%-81%]). With a median follow-up of 10.9 yrs, there was no additional CHF event. Therefore, the cumulative incidence of CHF remains to be 1.4% (95% confidence interval [95% CI], 1.36%- 7.7%). The 9 and 10 year DDFS rates were 89% (95% CI, 78%-94%) and 87% (95% CI 75%-93%), respectively. Conclusions: Longer follow-up of this study has demonstrated that ddAC →TH is associated with a low risk of CHF and promising DDFS in patients with early-stage HER2-positive breast cancer.

scholarly journals Cardiotoxicity and Cardiovascular Biomarkers in Patients With Breast Cancer: Data From the GeparOcto‐GBG 84 Trial

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Alexandra Maria Rüger ◽  
Andreas Schneeweiss ◽  
Sabine Seiler ◽  
Hans Tesch ◽  
Marion van Mackelenbergh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Early Stage ◽  
High Sensitivity ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Cardiac Troponin T ◽  
Cancer Data ◽  
Dose Dense

Background Patients with breast cancer can be affected by cardiotoxic reactions through cancer therapies. Cardiac biomarkers, like NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and high‐sensitivity cardiac troponin T, might have predictive value. Methods and Results Echocardiography, ECG, hemodynamic parameters, NT‐proBNP and high‐sensitivity cardiac troponin T were assessed in 853 patients with early‐stage breast cancer randomized in the German Breast Group GeparOcto‐GBG 84 phase III trial. Patients received neo‐adjuvant dose‐dense, dose‐intensified epirubicin, paclitaxel, and cyclophosphamide (iddEPC group, n=424) or paclitaxel, non‐pegylated doxorubicin, and in triple negative breast cancer, (paclitaxel, non‐pegylated doxorubicin, carboplatin group, n=429) treatment for 18 weeks. Patients positive for human epidermal growth receptor 2 (n=354, 41.5%) received monoclonal antibodies on top of allocated therapy; 119 (12.9%) of all patients showed a cardiotoxic reaction during therapy (15 [1.8%] using a more strict definition). Presence of cardiotoxic reactions was irrespective of treatment allocation ( P =0.31). Small but significant increases in NT‐proBNP developed early in patients with a cardiotoxic reaction as compared with those without in whom NT‐proBNP rose only towards the end of therapy ( P =0.04). High‐sensitivity cardiac troponin T rose early in both groups. Logistic regression showed that NT‐proBNP (odds ratio [OR], 1.03; 95% CI, 1.008–1.055; P =0.01) and hemoglobin (OR, 1.31; 95% CI, 1.05–1.63; P =0.02) measured at 6 weeks after treatment initiation were significantly associated with cardiotoxic reactions. Conclusions NT‐proBNP and hemoglobin are significantly associated with cardiotoxic reactions in patients with early‐stage breast cancer undergoing dose‐dense and dose‐intensified chemotherapy, but high‐sensitivity cardiac troponin T is not. Registration URL: http://www.clinicaltrials.gov ; Unique identifier: NCT02125344.

scholarly journals SWOG S0221: A Phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer

2015 ◽  
Vol 33 (1) ◽  
pp. 58-64 ◽  
Author(s):  
George T. Budd ◽  
William E. Barlow ◽  
Halle C.F. Moore ◽  
Timothy J. Hobday ◽  
James A. Stewart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Hormone Receptor ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Original Design ◽  
Significant Difference

Purpose To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. Patients and Methods A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome. Results Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor–negative/human epidermal growth factor receptor 2 (HER2) –negative tumors (P = .067), with no differences seen with hormone receptor–positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40). Conclusion Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor–negative/HER2-negative tumors.

scholarly journals Dose-Dense Epirubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Chemotherapy in Node-Positive Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hamid Reza Mirzaei ◽  
Parisa Sabet Rasekh ◽  
Fatemeh Nasrollahi ◽  
Parto Sabet Rasekh ◽  
Zahra Akbari Tirabad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Febrile Neutropenia ◽  
Optimal Dose ◽  
Axillary Lymph ◽  
Node Positive ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement particularly in node-positive patients, but optimal dose and schedule remain undetermined.Objectives. This study aimed to assess the feasibility of dose-dense epirubicin and cyclophosphamide followed by docetaxel in node-positive breast cancer.Methods. All Patients first received 4 cycles of epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) at 2-week interval then followed by docetaxel (100 mg/m2) at 2-week interval for 4 cycles, with daily Pegfilgrastim (G-CSF) that was administered in all patients on days 3–10 after each cycle of epirubicin and cyclophosphamide infusion.Results. Fifty-eight patients with axillary lymph node-positive breast cancer were enrolled in the study, of whom 42 (72.4%) completed the regimen. There were two toxicity-related deaths, one patient due to grade 4 febrile neutropenia and the other due to congestive heart failure. Grade 3/4 neutropenia and febrile neutropenia were 13.8% and 5.1%. The most common grade 3/4 nonhematological complications were as follows: skin-nail disorders (48.3%), hand-foot syndrome (34.4%), paresthesia (38%), arthralgia (27.5%), and paresis (24.1%).Conclusions. Dose-dense epirubicin and cyclophosphamide followed by docetaxel with G-CSF support are not feasible, and it is not recommended for further investigation.

Sign in / Sign up

Export Citation Format

Share Document