[Thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in soft-tissue sarcoma versus capecitabine potential].

Expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) can predict for clinical outcome of fluoropyrimidine-based therapy and there is every likelihood that relevant tumors will respond. High TP expression was observed in 35 (42%) patients with soft-tissue sarcoma. Seven out of 26 (27%) such patients revealed molecular phenotype prognostically favorable for capecitabine therapy. More clinical research is required to assess the efficacy of capecitabine-based therapy.

[Expression of epidermal growth factor receptor (EGFR) in ovarian carcinoma stage III-IV].

Hyperexpression of epidermal growth factor receptor (EGFR) is often identified as unfavorable prognosis for different epithelial cancers. The study was concerned with an attempt of establishing a relationship between EGFR expression, on the one hand, and patient's clinico-morphological status, prognosis and efficacy of chemotherapy for stage III-IV serous ovarian carcinoma, on the other. EGFR hyperexpression predominated in advanced aggressive tumors and involved a significantly shorter period preceding tumor progression. Similarly, overall survival median in patients with EGFR hyperexpression (21+/-4 months) appeared lower than without it (42+/-8 months). In serous ovarian carcinoma stage III-IV, EGFR hyperexpression should be considered sufficient for prognosis of chemotherapy efficacy, pre-progression time and survival.

Oral ibandronate for the treatment of metastatic bone disease in breast cancer: efficacy and safety results from a randomized, double-blind, placebo-controlled trial.

BACKGROUND: We report the first results of a randomized trial assessing a new oral aminobisphosphonate, ibandronate, in patients with bone metastases from breast cancer. PATIENTS AND METHODS: Patients (n = 435) received placebo, or oral ibandronate 20 mg or 50 mg once-daily for 96 weeks. The primary efficacy measure was the number of 12-week periods with new bone complications [skeletal morbidity period rate (SMPR)]. Multivariate Poisson regression analysis assessed the relative risk reduction of skeletal-related events. Secondary efficacy analyses included bone pain and analgesic use. Adverse events were monitored. RESULTS: SMPR was significantly reduced with oral ibandronate [placebo 1.2, 20 mg group 0.97 (P = 0.024), 50 mg group 0.98 (P = 0.037)]. Ibandronate 50 mg significantly reduced the need for radiotherapy (P = 0.005 versus placebo). The relative risk of skeletal events was reduced by 38% (20 mg dose) and 39% (50 mg dose) versus placebo (P = 0.009 and P = 0.005). The tolerability profile of ibandronate was similar to placebo. CONCLUSIONS: Oral ibandronate is an effective and well-tolerated treatment for metastatic bone disease. The 50 mg dose is being further evaluated in clinical trials, and this dose was recently approved in the European Union for the prevention of skeletal events in patients with breast cancer and bone metastases.

Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies.

Although intravenous (i.v.) bisphosphonates are the standard of care for metastatic bone disease, they are less than ideal for many patients due to infusion-related adverse events (AEs), an increased risk of renal toxicity and the inconvenience of regular hospital visits. The use of oral bisphosphonate therapy is limited by concerns over efficacy and gastrointestinal (GI) side effects. There remains a clinical need for an oral bisphosphonate that offers equivalent efficacy to i.v. bisphosphonates, good tolerability and dosing convenience. Oral ibandronate, a highly potent, third-generation aminobisphosphonate, has been evaluated in phase III clinical trials of patients with bone metastases from breast cancer. In two pooled phase III studies, patients with breast cancer and bone metastases were randomised to receive oral ibandronate 50 mg (n=287) or placebo (n=277) once daily for up to 96 weeks. The primary end point was the skeletal morbidity period rate (SMPR), defined as the number of 12-week periods with new skeletal complications. Multivariate Poisson's regression analysis was used to assess the relative risk of skeletal-related events in each treatment group during the study period. Oral ibandronate 50 mg significantly reduced the mean SMPR compared with placebo (0.95 vs 1.18, P=0.004). There was a significant reduction in the mean number of events requiring radiotherapy (0.73 vs 0.98, P<0.001) and events requiring surgery (0.47 vs 0.53, P=0.037). Poisson's regression analysis confirmed that oral ibandronate significantly reduced the risk of a skeletal event compared with placebo (hazard ratio 0.62, 95% CI=0.48, 0.79; P=0.0001). The incidence of mild treatment-related upper GI AEs was slightly higher in the oral ibandronate 50 mg group compared with placebo, but very few serious drug-related AEs were reported. Oral ibandronate 50 mg is an effective, well-tolerated and convenient treatment for the prevention of skeletal complications of metastatic bone disease.