Nab-Paclitaxel monotherapy as a treatment of patients with metastatic breast cancer in routine clinical practice.

AIM: To compare treatment results with use of nab-paclitaxel in routine clinical practice with data obtained from clinical trials. PATIENTS AND METHODS: A retrospective chart review of all 36 patients with metastatic breast cancer treated with nab-paclitaxel was performed. Nab-paclitaxel was given weekly and usually started at 150 mg/m(2). RESULTS: Thirteen (36.1%) patients received nab-paclitaxel as first-line, seven (19.4%) as second-line and 16 as third- or further line treatment. Overall, the response rate was 9.7%, disease control rate 64.5%, median progression-free survival 7.5 months and median overall survival 14.2 months. The most frequent non-hematological toxicities of grade 3 or more were fatigue (27.8%), dyspnea, rash and arthalgia (all 5.6%). Six (16.7%) patients developed peripheral neuropathy of grade 2 or more. Incidence of neutropenia grade 3 or more was 41.7% with no case of febrile neutropenia. CONCLUSION: According to our experience, weekly nab-paclitaxel is effective and tolerable, with results at least comparable to those from the prospective clinical trials.

Omission of axillary dissection according to ACOSOG Z0011: impact on adjuvant treatment recommendations.

OBJECTIVE: A recent, randomized trial (ACOSOG Z0011) has demonstrated that omission of completion axillary lymph node dissection (ALND) in patients with one or two sentinel lymph node (SLN) metastases treated with breast conserving therapy (BCT) does not have a negative impact on survival. This study evaluates the impact of omitting ALND on adjuvant treatment recommendations. METHODS: Performing a search of our clinical database, we identified patients meeting the main inclusion and exclusion criteria of ACOSOG Z0011 treated at the University of Heidelberg Breast Center. We performed blinded mock interdisciplinary tumor boards based on patient and tumor characteristics as well as (1) SLN information or (2) final nodal status after ALND. Differences between treatment recommendations were noted and analyzed. RESULTS: A total of 132 patients were included; 80.3 % of these had one and 19.7 % had two metastatic sentinel nodes with a rate of micrometastases only of 19.7 %, and 39.7 % of patients had additional nonsentinel node metastases upon ALND. Overall, there was a change in adjuvant chemotherapy in 18.2 % of cases. Treatment recommendations based on ALND lead to a more aggressive therapy in 16.6 % of cases, all of them with additional metastatic nonsentinel nodes. Chemotherapy was not recommended in only two cases (1.5 %) based on ALND. Based on ALND, irradiation of the supraclavicular and infraclavicular nodes was added in 5.3 % of patients. CONCLUSIONS: Completion ALND for patients with one or two metastatic sentinel nodes in pT1-2 cN0 PBC treated with BCT does have a relevant impact on adjuvant treatment. This should be considered in shared decision making.

Neoadjuvant epirubicin, gemcitabine and docetaxel for primary breast cancer: long-term survival data and major prognostic factors based on two consecutive neoadjuvant phase I/II trials.

We previously reported primary endpoints of two consecutive phase I/II trials, evaluating different schedules of neoadjuvant epirubicin (E), gemcitabine (G) and docetaxel (Doc) for primary breast cancer (PBC). Here, we report mature survival data and prognostic factors. One hundred fifty-one patients were recruited into two consecutive phase I/II trials of neoadjuvant chemotherapy for T2-4 N0-2 M0 PBC. Patients received six cycles of G/E/Doc every 3 weeks with G repeated on d8 (GEDoc, n = 84) or five cycles of G/E followed by four cycles of Doc all given every two weeks (GEsDoc, n = 67). Prognostic factors were investigated using univariate and multivariate analyses. No survival differences by treatment were found. Among reported predictive factors for pathologic complete response (pCR), oestrogen receptor (ER) status was the only relevant factor in the multivariate analysis. Unexpectedly, pCR resulted in poorer survival (univariate HR for overall survival [OS] 3.11, p = 0.007). Multivariate analyses identified molecular subtype and tumour size as the most relevant prognostic factors for OS. HER2-receptor status and the CPS-EG score (Mittendorf et al., J Clin Oncol 2011;29:1956-62), based on clinical and pathological stage, ER-status and tumour grade, were particularly relevant in disease-free survival. Our findings cast doubt on the reliability of pCR as single marker for prognosis of this unselected breast cancer cohort, with an abundance of luminal subtypes. These results underline the significance of additional molecular characteristics for breast cancer survival.

Long-term remission in a patient with heavily pretreated, advanced ovarian cancer achieved by bevacizumab and metronomic cyclophosphamide treatment.

Vascular endothelial growth factor seems to be a promoter of tumor progression for epithelial ovarian cancer. New drugs such as bevacizumab, either alone or in combination with metronomic chemotherapy, suppress tumor growth and have proved to be effective in various tumor types. We present a 60-year-old patient with heavily pretreated, recurrent epithelial ovarian cancer, who received bevacizumab (10 mg/m(2)) every 2 weeks in combination with metronomic administered low-dose cyclophosphamide (50 mg/day orally) after failing four explorative laparotomies and multiple chemotherapy regimes. At the time of writing, February 2011, she was being treated with this combination therapy for 24 months and the progression-free survival still continues. Treatment of advanced, refractory epithelial ovarian cancer with bevacizumab in combination with low-dose cyclophosphamide could be a very effective salvage treatment option in heavily pretreated patients.

Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial.

BACKGROUND: We compared the healing response of tibial delayed unions between subjects treated with low-intensity pulsed ultrasound (LIPUS) (n = 51) and subjects treated with a sham device (n = 50). Fracture age was ≥ 4 months in all cases. Study personnel and participants were blinded to random treatment assignment throughout the study. METHODS: This multi-center randomized sham-controlled trial was undertaken at six hospitals in Germany. Adult patients who had sustained a tibial shaft fracture that subsequently showed inadequate progress toward healing (i.e., delayed union) were enrolled and randomized to receive either LIPUS (Exogen 2000/2000+, Smith & Nephew GmbH, Schenefeld, Germany) or an identical nonoperative sham device. The daily treatment duration was 20 minutes, for a period of 16 weeks. Subjects randomly assigned to active treatment had the ultrasound pressure wave signal set at the following parameters: 1.5 MHz frequency, 1 kHz repetition rate, 200 µs pulse duration, 30 mW/cm2 spatial intensity. Progress toward healing was estimated from changes in bone mineral density (BMD) and gap area as determined from computed tomography scans. Intention-to-treat analysis was conducted using a multiple imputation methodology. RESULTS: Based on log-transformed data, mean improvement in BMD was 1.34 (90% confidence interval (CI) 1.14 to 1.57) times greater for LIPUS-treated subjects compared to sham (p = 0.002). A mean reduction in bone gap area also favored LIPUS treatment (p = 0.014). CONCLUSIONS: These findings demonstrate significantly greater progress toward bone healing after LIPUS treatment compared to no LIPUS treatment in subjects with established delayed unions of the tibia.