Compliance and persistence are often overlooked in adjuvant breast cancer treatment.
PACT was a prospective, multicenter, randomized, open, parallel-group study assessing whether educational ...materials (EMs) enhanced compliance with aromatase inhibitor (AI) therapy in postmenopausal women with early, hormone-receptor-positive (HR+) breast cancer. The primary end points were compliance (proportion taking ≥80% anastrozole) at 12 months and persistence (proportion reporting anastrozole intake during the study period).
Four thousand eight hundred and forty-four patients were randomly assigned 1:1 to receive standard therapy or standard therapy with EMs. There was no difference between arms in compliance (N = 2740; 88.5%/88.8%, respectively, P = 0.81) or persistence rates (N = 2740; 40.5%/43.0%, respectively, P = 0.18). Modified end point analyses found no differences in compliance between arms based on the classification of: (i) patients with missing documentation or follow-up visit <9 months as non-compliant (N = 4397, P = 0.15); (ii) patients with early (≤292 days) 12-month follow-up documentation excluded (N = 4091, P = 0.19); (iii) patients reaching ≥80% compliance during individual follow-up as compliant (N = 4397, P = 0.26). Modified persistence analyses found no difference between arms (N = 4397, P = 0.37).
Addition of EMs to standard therapy did not significantly affect compliance and persistence with adjuvant anastrozole.
NCT00555867.
Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer. Strategies to improve efficacy include the use of anthracyclines, taxanes, and ...intensified dose with bone marrow support.
Patients received neoadjuvant epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 followed by paclitaxel 175 mg/m2 (EC→T), each 3-weekly for four cycles (n=370), or epirubicin 150 mg/m2 followed by paclitaxel 225 mg/m2 with pegfilgrastim followed by CMF (cyclophosphamide 500 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2) on days 1 and 8 (Edd→Tdd→CMF), each 2-weekly and for three cycles (n=363). Patients were randomly allocated to either simultaneous darbepoetin alfa (DA) (n=356) or none (n=377).
Pathological complete response (pCR) rate (breast) was higher with Edd→Tdd→CMF, 18.7% versus 13.2% with EC→T; P=0.043, ypT0/Tis; ypN0 was reported in 20.9% versus 14.3% respectively; P=0.019. Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate. Mean hemoglobin values maintained higher with DA (13.6 versus 12.6 g/dl). Edd→Tdd→CMF regimen showed more grade 3–4 mucositis, sensory neuropathy, and neurological complaints. Thromboembolic events were more frequent on DA (3% versus 6%; P=0.055).
Dose-dense and -intensified neoadjuvant chemotherapy with Edd→Tdd→CMF was potentially superior to EC→T in terms of pCR. Primary use of DA did not affect pCR.
The presence of disseminated tumor cells (DTCs) in bone marrow of patients with early breast cancer (EBC) has been correlated with increased risk of metastatic disease or locoregional relapse. ...Zoledronic acid (ZOL) treatment has reduced DTCs in the bone marrow of patients with EBC in several studies. This controlled study sought to confirm these observations.
Patients with EBC and DTC-positive bone marrow were randomized (N=96) to treatment with ZOL plus adjuvant systemic therapy or adjuvant systemic therapy alone. The change in DTC numbers at 12 months versus baseline was measured.
DTC-positive patients treated with ZOL were more likely to become DTC-negative after 12 months of treatment compared with the controls (67% versus 35%; P=0.009). At 12 months, DTC counts decreased to a mean of 0.5±0.8 DTCs in the ZOL group and to 0.9±0.8 DTCs in the control group. In addition, ZOL was generally well tolerated.
Treatment with ZOL improves elimination of DTCs. Further studies are needed to determine whether the reduction in DTCs by ZOL provides clinical benefit.
Longitudinal control signals used to keep gravitational wave detectors at a stable operating point are often affected by modulations from test mass misalignments leading to an elevated noise floor ...ranging from 50 to 500 Hz. Nonstationary noise of this kind results in modulation sidebands and increases the number of glitches observed in the calibrated strain data. These artifacts ultimately affect the data quality and decrease the efficiency of the data analysis pipelines looking for astrophysical signals from continuous waves as well as the transient events. In this work, we develop a scheme to subtract one such bilinear noise from the gravitational wave strain data and demonstrate it at the GEO 600 observatory. We estimate the coupling by making use of narrow-band signal injections that are already in place for noise projection purposes and construct a coherent bilinear signal by a two-stage system identification process. We improve upon the existing filter design techniques by employing a Bayesian adaptive directed search strategy that optimizes across the several key parameters that affect the accuracy of the estimated model. The scheme takes into account the possible nonstationarities in the coupling by periodically updating the involved filter coefficients. The resulting postoffline subtraction leads to a suppression of modulation sidebands around the calibration lines along with a broadband reduction of the midfrequency noise floor. The observed increase in the astrophysical range and a reduction in the occurrence of nonastrophysical transients suggest that the above method is a viable data cleaning technique for current and future generation gravitational wave observatories.
Background: Capecitabine is a rationally designed oral, tumor-activated fluoropyrimidine carbamate with high activity in metastatic breast cancer. This multicenter phase II study was designed to ...evaluate further the efficacy and safety of capecitabine in patients with metastatic breast cancer previously treated with a taxane-containing regimen. Patients and methods: All patients had to have documented progression after paclitaxel- or docetaxel-containing chemotherapy. Treatment comprised 3-week cycles of oral capecitabine 1250 mg/m2 twice-daily for 14 days followed by a 7-day rest period. Results: One hundred and thirty-six patients were enrolled. Disease stabilization occurred in 63 patients (46%) and the overall response rate was 15% (95% confidence interval 10% to 23%), providing an overall tumor control rate of 62%. Median time to progression was 3.5 months, median duration of response was 7.5 months and median overall survival was 10.1 months. Capecitabine was generally well-tolerated: most treatment-related adverse events were grade 1/2 in intensity; grade 3/4 treatment-related adverse events were hand–foot syndrome (13%), diarrhea (8%), vomiting (4%) and nausea (3%). There were no treatment-related deaths. Conclusions: This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated patients with metastatic breast cancer. Due to its favorable safety profile and convenient oral administration, capecitabine can be given as an outpatient therapy. Capecitabine should be considered the reference treatment in this setting based on consistently high efficacy and good tolerability.
The objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of standard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or ...without darbepoetin on survival in primary breast cancer.
A total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks followed by four cycles of paclitaxel 175 mg/m2 every 3 weeks (EC→T), or three cycles of epirubicin 150 mg/m2 every 2 weeks followed by three cycles of paclitaxel 225 mg/m2 every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (Edd→Tdd→CMF). The patients were randomly assigned to receive darbepoetin or none. The primary objective was to demonstrate a superior disease-free survival (DFS) of Edd→Tdd→CMF compared with EC→T.
Estimated 3-year DFS was 75.8% with EC→T versus 78.8% with Edd→Tdd→CMF hazard ratio (HR) 1.14; P = 0.37 and overall survival (OS) 88.4% versus 91.5% (HR 1.26; P = 0.237). Three-year DFS was 74.3% with darbepoetin versus 80.0% without (HR 1.31; P = 0.061) and OS 88.0% versus 91.8% (HR 1.33; P = 0.139). Patients with a pathologically documented complete response pathological complete response (pCR) had a significantly better DFS compared with those without achieving a pCR (estimated 3-year DFS: 89.2% versus 74.9%; HR 2.27; P = 0.001).
Neoadjuvant dose-intensified chemotherapy compared with standard chemotherapy did not improve DFS, whereas the addition of darbepoetin might have detrimental effects on DFS.
Dose-dense (dd) regimens are one of the preferred options for the adjuvant treatment of breast cancer patients with intermediate to high risk. The German Adjuvant Intergroup Node-positive trial aimed ...at optimizing intense dd (idd) strategies by evaluating drug combinations and the addition of capecitabine.
Women (aged 18 years and biologically <65 years) with histologically involved axillary lymph nodes were randomly assigned to receive three courses each of epirubicin (E) 150 mg/m2, paclitaxel (P) 225 mg/m2 and cyclophosphamide (C) 2500 mg/m2 (reduced to 2000 mg/m2 after recruitment of 1200 patients) q2w intravenously (i.v.) (iddEPC-regimen) or ddEC (E 112.5 mg/m2 + C 600 mg/m2, i.v. q2w for 4 cycles) followed by paclitaxel weekly (Pw 67.5 mg/m2 i.v. q8d for 10 weeks) plus capecitabine (X 2000 mg/m2 p.o. days 1–14, q22 for 4 cycles) (ddEC-PwX-regimen). Further randomization assigned patients to ibandronate for 2 years versus observation and to pegfilgrastim day 2 versus 4.
From June 2004 to August 2008, 2994 patients were randomized to either iddEPC (N = 1498), or ddEC-PwX (N = 1496) and started treatment. Median age was 50 years; pN1 (37.8%), pN2 (35.3%); pN3 (26.9%); 46.4% were G3 tumors; 76.9% hormone receptor-positive and 22% HER2-positive. After a median follow-up of 74 months, 645 events and 383 deaths were recorded. Hematological adverse events grades 3–4 were more common with iddEPC (P < 0.001), nonhematological with ddEC-PwX (P = 0.04), even if the toxicity profile of the two regimens was different. At 5 years, estimated disease-free survival rates for ddEC-PwX and iddEPC were 81.7% 95% confidence interval (CI) 79.5–83.6 versus 80.2% (95% CI 78.0–82.2). Hazard ratio (HR)=0.95 (95% CI 0.81–1.11, log-rank P = 0.49). Five-year overall survival rates were 89.4% for ddEC-PwX (95% CI 87.7–91.0) and 89.0% for iddEPC (95% CI 87.2–90.6), HR = 0.85 (95% CI 0.69–1.04, log-rank P = 0.10).
Adding capecitabine to ddEC-Pw did not improve outcome in comparison to iddEPC but increased toxicity and should not be recommended for further use.
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