Bevacizumab in the treatment of patients with advanced breast cancer: where have we landed?

Vast preclinical and clinical evidence has made angiogenesis one of the hallmarks of cancer. In many human tumours, vascular endothelial growth factor (VEGF) has been identified as the crucial mediator of this process. Initial studies suggested that angiogenesis, and VEGF in particular, could be inhibited without the risk of major side effects. After the pivotal data in first-line studies in patients with colorectal cancer, numerous clinical trials have been undertaken in patients with breast cancer. This review attempts to update these investigations and define the role of anti-VEGF antibody treatment in advanced breast cancer.

High activity and tolerability demonstrated for exemestane in postmenopausal women with metastatic breast cancer who had previously failed on tamoxifen treatment.

This phase II, multicentre, open-label, clinical trial evaluated antitumoral efficacy, tolerability and endocrine effects following 25 mg of treatment with oral exemestane given daily to postmenopausal women with metastatic breast cancer. Eligibility criteria included oestrogen and/or progesterone positivity or a prior response to hormonal therapy if receptor status was unknown; prior failure to tamoxifen therapy; and progressive disease. Patients were divided into three strata: patients who did not respond to tamoxifen or progressed after disease stabilisation (SD) for less than 6 months (stratum 1); patients who, after an initial response or SD lasting at least 6 months, experienced disease progression whilst on tamoxifen (stratum 2); patients with recurrent metastatic disease during or within 12 months of discontinuing adjuvant tamoxifen (stratum 3). Of the 137 patients who received exemestane, 4 experienced a complete response (CR) and 28 a partial response (PR), for an overall response rate of 23%. Another 33 patients had SD for > or = 24 weeks, resulting in an overall success rate of 47%. The median time to objective response was 16.1 weeks (95% confidence interval (CI) 9.9-24.1). The median response duration was 69.4 weeks, the median duration of overall success 59.1 weeks, the median time to progression (TTP) 25.1 weeks and the median time to treatment failure (TTF) 24 weeks. Response to previous hormonal therapy had little effect on the results, except that there was a trend toward a higher overall success rate in patients who did not respond to previous hormonal therapy. After 8 weeks of therapy, serum levels of oestradiol (E2), oestrone (E1) and oestrone sulphate (E1S) were suppressed to 15.2%, 9.7% and 10.7% of baseline, respectively. The most common adverse events of drug-related or indeterminate cause were hot flushes (14%), dizziness (9%), nausea (8%) and increased sweating (5%). Exemestane had a favourable effect on performance status and tumour-related signs and symptoms, both of which improved or stabilised in approximately 67% and 68% of patients respectively. Exemestane is a unique therapy that is highly active and well tolerated as a new treatment for women with metastatic breast cancer.

A phase II trial with docetaxel (Taxotere) in second line treatment with chemotherapy for advanced breast cancer. A study of the EORTC Early Clinical Trials Group.

BACKGROUND: Docetaxel, a semisynthetic analog of paclitaxel, made for the needles of the European yew, Taxus baccata, is a potentially important chemotherapeutic agent for the treatment of cancer. PATIENTS AND METHODS: In a phase II study patients with advanced and/or metastatic breast cancer and bidimensionally measurable disease, were treated with docetaxel 100 mg/m2 every 3 weeks as a 1 hour infusion without any premedication. Treatment was evaluated after 2 courses and every 2 subsequent courses. RESULTS: Thirty-nine patients were entered, 32 were eligible. The eligible patients had a median age of 51 years (range 30-73) and a performance status WHO 1 median, (range 0-2). Twenty-eight patients had been treated with surgery, 24 with radiation. Hormonal treatment was previously given in 23, chemotherapy in 32. Of 24 patients treated as second line strategy, 13 achieved a partial remission, 1 a complete remission (overall response rate 58% (95% CI 37%-78%)). Eight patients treated as first line: 2 PR's, 1 CR. The median overall response duration was 38 weeks. The main toxicity consisted of transient grade 4 neutropenia in 149 of 167 evaluable courses (89%). However, the related infection rate was low. Re-treatment at 3 weeks, as scheduled, was nearly always possible. Other toxicities consisted of skin reactions (81%) and nail changes (41%), neurosensory toxicity (59%) and occasionally hypersensitivity reactions (16%). Fluid retention was a toxicity of major concern, observed in 59% of patients. CONCLUSION: Docetaxel is a very active drug against breast cancer. Further studies are required to alleviate the non-hematological toxicities.

Respiratory insufficiency in acid maltase deficiency: the effect of high protein diet.

A 27-yr-old woman with the myopathic form of acid maltase deficiency (AMD) developed severe respiratory insufficiency after a crash diet resulting in a 6-kg weight loss. While being maintained on home ventilation, an hypercaloric high-protein, low-carbohydrate diet (1800-2000 cal; 28% carbohydrates, 55% fat, 17% protein with 1.7 g protein/kg body weight) was instituted. This ameliorated her condition up to a level where useful life was possible and ventilation could be diminished.