A prospective randomised phase II trial of thalidomide with carboplatin compared with carboplatin alone as a first-line therapy in women with ovarian cancer, with evaluation of potential surrogate markers of angiogenesis.

OBJECTIVES: To compare the safety and efficacy of thalidomide in combination with carboplatin to carboplatin alone as a first-line therapy in women with ovarian cancer and to evaluate the anti-angiogenic effects of thalidomide by measurement of surrogate markers of angiogenesis. METHODS: Forty patients with Stage IC-IV ovarian cancer were randomly assigned to receive either carboplatin (AUC 7) intravenously every four weeks for up to six doses (n = 20) or carboplatin at the same dose and schedule, plus thalidomide 100 mg orally daily for six months (n = 20). RESULTS: After median follow-up of 1.95 years, there was no difference in the overall response rate (90% in carboplatin arm, 75% in combination arm; p = 0.41). Increased incidence of symptoms of constipation, dizziness, tiredness and peripheral neuropathy was observed in the combination arm. There was a significant fall in CA-125 and E-selectin in both arms after treatment and VCAM-1 in the carboplatin arm. No significant difference between the two arms was observed in any of the markers analysed. CONCLUSIONS: In our trial the addition of thalidomide to carboplatin was well tolerated with no increased efficacy. The fall in some of the angiogenic markers in both groups may reflect tumour response rather than any specific anti-angiogenic effect of thalidomide.

Management of patients with hormone refractory prostate cancer.

Prostate cancer is the second most common cancer in men in the UK, and the incidence of prostate cancer has increased dramatically over the past two decades. Although most men are diagnosed at early stage, more than 50% develop locally advanced or metastatic disease. Androgen ablation with luteinising hormone-releasing hormone (LHRH) agonists alone, or in combination with anti-androgens, is the standard treatment for men with metastatic prostate cancer. Unfortunately, almost all men develop progressive disease after a variable time period, despite the maximal androgen blockade. The management of hormone refractory prostate cancer (HRPC) is challenging, as there is no uniformly accepted strategy. Various treatment options, including second-line hormone therapy, are discussed. Chemotherapy is being increasingly used and, importantly, docetaxel and estramustine may play an important role in the near future. The role of radiotherapy, strontium-89, bisphosphonates, novel agents and future therapies are also outlined.