Second-Line Treatment of Metastatic Prostate Cancer. Prednisone and Radiotherapy for Symptom Relief.

Second-line treatment of metastatic prostate cancer. Prednisone and radiotherapy for symptom relief.

Prescrire Int. 2013 Mar; 22(136): 74-8

First-line treatment based on androgen suppression is initially very effective in relieving the symptoms of metastatic prostate cancer. When androgen suppression no longer controls disease progression and symptoms, which treatments are known to improve duration or quality of survival? To answer this question, we reviewed the evidence using the standard Prescrire methodology. Low doses of corticosteroids, such as prednisone 5 to 10 mg per day, appear to improve quality of life for a few months by relieving symptoms in 20% to 40% of patients. When added to prednisone, docetaxel, a cytotoxic drug, tends to be more effective than mitoxantrone in terms of pain relief and quality of life. Docetaxel prolongs survival by about 2 months but provokes severe adverse effects in one-quarter of patients. Adding estramustine to this combination prolongs survival but carries a risk of serious thromboembolic events. Addition of bevacizumab has no proven impact on survival. After failure of cytotoxic chemotherapy with docetaxel, two hormonal treatments, abiraterone and enzalutamide, appear to prolong survival by about 4 or 5 months, and are associated with moderate adverse effects. However, these results are based on only one trial of each drug. Cabazitaxel is also moderately effective in terms of survival but has a less favourable adverse effect profile than abiraterone. A meta-analysis of trials of bisphosphonates used to prevent complications of bone metastases showed no major benefit, including in terms of pain relief. Bisphosphonates are not sufficiently effective to justify exposing patients to their potentially serious adverse effects. In one trial, the harm-benefit balance of denosumab was no better than that of zoledronic acid, a bisphosphonate. External beam radiation therapy or intravenous infusion of strontium-89 (a radioisotope) each relieves pain associated with bone metastases in over 70% of cases. If metastatic prostate cancer progresses despite androgen suppression, the two main options in 2012 are either: palliative treatment with corticosteroids and external beam radiation therapy or radioisotope infusion; or docetaxel followed by abiraterone, which slightly prolongs survival but at a cost of sometimes serious adverse effects. HubMed – drug

Bevacizumab and advanced-stage ovarian cancer. Yet another oncological indication, but still best to avoid using this drug.

Prescrire Int. 2013 Mar; 22(136): 64-7

Epithelial ovarian, fallopian tube and primary peritoneal malignancies are treated in much the same way. Treatment for women with advanced-stage disease consists of surgical resection followed by platinum-based chemotherapy. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor, is authorised in the European Union for the treatment of various malignancies. It was approved for first-line treatment of advanced-stage epithelial ovarian cancer, in combination with chemotherapy consisting of carboplatin + paclitaxel. Two trials involving a total of about 3400 women have evaluated the addition of bevacizumab in women receiving carboplatin + paclitaxel chemotherapy. In mid-2012, no statistically significant impact on median overall survival had emerged. Median “progression-free” survival was significantly prolonged when bevacizumab was added both during and after chemotherapy, by 4.1 months with 15 mg/kg and 2.4 months with 7.5 mg/kg. In one trial, “progression” was defined using laboratory or radiological parameters, but not necessarily clinical events. There was no statistically significant increase in “progression-free” survival when bevacizumab was only given during chemotherapy. continue treatment for adverse events, and also more likely to experience serious, sometimes fatal, adverse effects. The most frequent adverse effects of bevacizumab included haemorrhage, arterial hypertension, and gastrointestinal perforation. In practice, following surgery for advanced-stage epithelial ovarian cancer, it is best not to add bevacizumab to first-line chemotherapy. HubMed – drug

Topiramate + phentermine. An excessively dangerous appetite-suppressant combination.

Prescrire Int. 2013 Mar; 22(136): 61-4

The cornerstones of treatment for obesity, and even more so for simple overweight, are dietary measures and physical exercise. There are no drugs with a favourable harm-benefit balance in this setting. A fixed-dose combination of topiramate, an antiepileptic drug, and phentermine, an appetite-suppressant amphetamine, has been refused marketing authorisation in the European Union, after being licensed in the United States. There are no randomised controlled trials of topiramate + phentermine in the prevention of complications of obesity. In the three available placebo-controlled trials, patients treated with topiramate 46 mg per day + phentermine 7.5 mg per day for between 1 and 2 years lost about 6-8 kg more than patients who received a placebo. About one-quarter of this weight loss was regained within a year after treatment discontinuation. The known adverse effects of the two drugs composing this combination are additive, and include psychiatric disorders, cardiac arrhythmias and metabolic acidosis. The risk of serious cardiovascular disorders was not adequately studied during clinical trials. Many women of child-bearing age would be exposed to this combination, which can provoke fetal abnormalities, including cleft palate, if taken during pregnancy. In practice, the topiramate + phentermine combination has an unfavourable harm-benefit balance and has no place in the treatment of obesity. HubMed – drug