Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.

BACKGROUND: Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced, hormone-refractory prostate cancer, but it does not improve survival. We compared such treatment with docetaxel plus prednisone in men with this disease. METHODS: From March 2000 through June 2002, 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were randomly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks, 75 mg of docetaxel per square meter every three weeks, or 30 mg of docetaxel per square meter weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, prostate-specific antigen (PSA) levels, and the quality of life. All statistical comparisons were against mitoxantrone. RESULTS: As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel. CONCLUSIONS: When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.

Inhibition of EGFR tyrosine-kinase in NSCLC treatment: the Hungarian experience with gefitinib in the context of an expanded access programme.

The ZD1839 (Iressa, gefitinib) treatment in phase I trials for patients with advanced non-small cell lung cancer (NSCLC) was associated with disease stabilization and tumor regression. The aim of this study was to analyze the efficacy of gefitinib monotherapy as a second- or third-line treatment for locally-advanced and advanced NSCLC. Data for 50 patients were analyzed. Patients were treated at 5 centers in Hungary as part of the gefitinib Expanded Access Programme (EAP). The response rate was 10% (all partial responses), with disease stabilization in 46% of patients. Disease progression was observed in 44% of patients. The median survival according to the Kaplan-Meier method was 8 months. Median survival of patients with adenocarcinoma was significantly increased compared with squamous cell carcinoma and, of the patients responding to therapy, 80% had adenocarcinoma. The 1-year survival rate was 34%. All patients were evaluable for safety; the adverse events seen with gefitinib were generally mild and only two patients had to be withdrawn from the study due to adverse events. The Hungarian experience suggests gefitinib therapy is effective and well tolerated.

[Effect of imatinib treatment of gastrointestinal stromal tumors]. / Az imatinibkezelés hatása gastrointestinalis stroma eredetú daganatokban.

INTRODUCTION: Advanced malignant gastrointestinal stromal tumours are practically resistant to further radio- or chemotherapy. These tumours are characterized by the presence of C-KIT (a transmembrane tyrosin kinase) mutation which can be specified by CD117 expression. Imatinib (2-fenilaminopirimidine) is a selective inhibitor of the mutated C-KIT. AIM: The purpose of our study was to determine the potential antitumour effect of imatinib in patients with gastrointestinal stroma tumour patients. MATERIALS AND METHODS: An open, non-randomized trial was performed involving 38 patients each of which had received/metastatic disease associated with CD117 positivity. Consecutively daily doses of 400-600 mg imatinib was administered orally to the patients. The evaluation was carried out on 37 patients in a form of an interim analysis. RESULTS: After a 3-18 months observation period 1 complete, 19 partial remissions and 10 static diseases could be registered (78%), in association of only grade 1-2 toxicity. CONCLUSIONS: The imatinib treatment improved the quality of life of the patients with gastrointestinal stroma tumour and their life expectancy became considerably prolonged. Further follow-up of the patients as well as design of a prospective, randomized trial on a larger patient material is urgently needed.

A randomized, double-blind, placebo-controlled phase II study of vandetanib plus docetaxel/prednisolone in patients with hormone-refractory prostate cancer.

Vandetanib (ZACTIMA) is a once-daily oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection signaling. This randomized (1:1), double-blind study evaluated vandetanib (100 mg/day) or placebo in combination with docetaxel (D; 75 mg/m(2) every 3 weeks) and prednisolone (P; 2 x 5 mg/day) in 86 patients with metastatic hormone-refractory prostate cancer (mHRPC). The primary assessment was prostate-specific antigen (PSA) response (confirmed reduction of >or=50% from baseline) and a greater number of patients showed a PSA response with placebo + DP (67%) versus vandetanib + DP (40%); hazard ratio = 2.23 (one-sided 80% confidence limit = 2.90; one-sided p = 0.99). More patients experienced progression events (disease progression or death from any cause) with vandetanib + DP (65%) versus placebo + DP (60%); hazard ratio = 1.13 (one-sided 80% confidence limit = 1.44; one-sided p = 0.67). The overall incidence of adverse events was similar in both groups, although more patients experienced adverse events, leading to permanent discontinuation with vandetanib + DP (28%) versus placebo + DP (12%). However, the safety and tolerability profile for vandetanib was similar to that previously reported; adverse events that occurred more frequently in the vandetanib + DP arm were hypertension (14% vs. 2%), erythematous rash (14% vs. 2%), and exfoliative rash (12% vs. 2%). In this study of patients with mHRPC, vandetanib + DP did not demonstrate any efficacy benefit, compared with placebo + DP.