Combination of bevacizumab and 2-weekly pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer. A multicenter, single-arm phase II trial (SAKK 24/06)

Background: Pegylated liposomal doxorubicin (PLD) and bevacizumab are active agents in the treatment of metastatic breast cancer (MBC). We carried out a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of PLD and bevacizumab as first-line treatment in MBC patients. Methods: Bevacizumab (10 mg/kg) and PLD (20 mg/m2) were infused on days 1 and 15 of a 4-week cycle for a maximum of six cycles. Thereafter, bevacizumab monotherapy was continued at the same dose until progression or toxicity. The primary objective was safety and tolerability, and the secondary objective was to evaluate efficacy of the combination. Results: Thirty-nine of 43 patients were assessable for the primary end point. Eighteen of 39 patients (46%, 95% confidence interval 30% to 63%) had a grade 3 toxicity. Sixteen (41%) had grade 3 palmar-plantar erythrodysesthesia, one had grade 3 mucositis, and one severe cardiotoxicity. Secondary end point of overall response rate among 43 assessable patients was 21%. Conclusions: In this nonrandomized single-arm trial, the combination of bimonthly PLD and bevacizumab in locally recurrent and MBC patients demonstrated higher than anticipated toxicity while exhibiting only modest activity. Based on these results, we would not consider this combination for further investigation in this settin

Femoral osteochondroplasty can be performed effectively without the risk of avascular necrosis or femoral neck fractures in an experimental ovine FAI model.

OBJECTIVE The experimental induction of cam-type femoroacetabular impingement (FAI) in sheep is established. To tap the full potential of this ovine model, one should be able to perform a femoral osteochondroplasty safely. This study was based on previous cadaver experiments on the blood supply to the ovine femoral head and on the biomechanical strength of the proximal femur following offset creation. We hypothesized that offset creation in this ovine FAI model does not lead to (1) avascular necrosis (AVN) of the ovine femoral head or (2) iatrogenic femoral neck fractures and (3) can be performed effectively. DESIGN In this experimental, controlled, prospective study nine sheep underwent unilateral FAI induction through an intertrochanteric, varus osteotomy. Seventy days following FAI induction, femoral osteochondroplasty was performed. Sheep were sacrificed after another 140 days. Radiographs, computed tomography (CT) scans and MRI were acquired. Histologic samples were stained with hematoxylin-eosin. (1) The multimodal Association Research Circulation Osseous (ARCO) classification was used for assessment of AVN. (2) Femoral neck fractures were assessed with the multimodal imaging approach. (3) Pre- and postoperative (=after sacrifice) alpha angles and femoral neck diameters were compared. RESULTS (1) No signs for AVN according to the ARCO classification or (2) for femoral neck fractures were detected. (3) Mean alpha angles and femoral neck diameters decreased significantly (p < 0.001) superiorly by at least 30° respectively 4 mm after the offset creation. CONCLUSIONS Femoral osteochondroplasty can be performed effectively and without the risk of AVN or femoral neck fractures in this ovine FAI model