Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.

Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44).

BACKGROUND: We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m(2); q3w) followed by four cycles docetaxel (100 mg/m(2); q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy. RESULTS: TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis. CONCLUSIONS: The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates.

Non-pegylated liposomal doxorubicin and docetaxel in metastatic breast cancer: final results of a phase II trial.

BACKGROUND: Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumor activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as single agent or in combination with cyclophosphamide, but there is limited experience with the combination of NPLD and taxanes. This phase II study was performed to evaluate the efficacy and safety of the NPLD and docetaxel in patients with metastatic breast cancer. PATIENTS AND METHODS: A total of 51 patients were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) in 3-weeks intervals for up to eight cycles. RESULTS: The overall response rate was 50% and 78% of patients derived a clinical benefit. Median time to progression and overall survival were 10.0 months (95% CI, 6.9-13.1 months) and 25 months (95% CI, 22.1-29.8 months), respectively. Median duration of response was 12.0 months (95% CI 7.1-16.9). The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents and of anthracycline/taxane combinations. There were no symptomatic cardiac averse events and mild asymptomatic LVEF changes were reported in five patients. CONCLUSIONS: The combination of NPLD and docetaxel is well tolerated and has high antitumour activity in MBC patients.

[Urine flow measurement in pregnancy and the puerperium]. / Harnflussmessungen in der Schwangerschaft und in Wochenbett.

To elucidate effects of gestation on micturition, 337 standardised urine flow measurements with weight transducers were performed on 296 women in normal pregnancy (n = 128), under oral or intravenous tocolysis (n = 103), after spontaneous delivery (n = 20) or obstetric surgery (n = 26) as well as on non-pregnant probands (n = 19) with clinically intact urinary tract for comparison. Average micturition frequency was calculated, as well (n = 86). However, only general trends were discernible from mean value calculations because of wide scatter of uroflow parameters: In normal pregnancy, significant increase in flow rate was observed only in the second trimenon. Major opposite effects were recordable from beta-adrenergics (Fenoterol) only in intravenous tocolysis. Micturition frequency was at its highest level towards the end of pregnancy. Post-partum, only flow rates after forceps delivery were worse than those in the non-pregnant control group, on the other hand after spontaneous delivery flow rates were even better than in the controls. Yet, even significant differences stayed within normal range, so that in general severe disadvantages should not be expected from voiding alterations during pregnancy. Uroflow measurements and frequency/volume charts are not required in the care of pregnant women unless conspicuous findings are derived from analyses of micturition habits, types, and frequencies.

[Metastasis of a spinal myxopapillary ependymoma to the inner auditory canal]. / Metastase eines spinalen myxopapillären Ependymoms im inneren Gehörgang.

Ependymomas are usually benign tumors of the central nervous system that derive from the ependymal cells lining liquor-filled spaces. Myxopapillary ependymomas are a variant occurring almost exclusively in the region of the cauda equina. Histologically, these tumors are benign (WHO grade I). The following case describes the first reported spread of a spinal myxopapillary ependymoma into the internal auditory canal. The symptoms and diagnostic results are similar to other tumors of this location. There are no typical findings in the diagnostic imaging (CT, MRI). The extended middle cranial fossa approach was chosen for surgical treatment. Adjuvant radiotherapy is indicated in cases of incomplete resection or recurrence.

[Cardiotocographic findings during expulsion (author's transl)]. / Kardiotokografische Befunde in der Austreibungsperiode.

The cardiotocographic findings recorded from 146 expulsions were analysed and related to the condition of the newborns. Melchior's cardiotocographic distribution diagram proposed for the expulsion period, 1973, is checked for its applicability.

[Kasabach-Merritt syndrome]. / Das Kasabach-Merritt-Syndrom.

The Kasabach-Merritt syndrome is a rare, congenital disease, characterized by giant haemangiomatosis and disseminated intravasal coagulation. It is reported on an at present 34-year-old patient with such a disease and the long-term course is described. Complications with haemorrhages can be prevented by means of anticoagulants.