Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer

A multicentre phase II trial was undertaken to evaluate the activity and toxicity of docetaxel plus cisplatin as first-line chemotherapy in patients with urothelial cancer. Thirty-eight patients with locally advanced or metastatic transitional-cell carcinoma of the bladder, renal pelvis or ureter received the combination of docetaxel 75 mg m−2 and cisplatin 75 mg m−2 on day 1 and repeated every 21 days, to a maximum of six cycles. The median delivered dose-intensity was 98% (range 79–102%) of the planned dose for both drugs. There were seven complete responses and 15 partial responses, for and overall response rate of 58% (95% CI, 41–74%). Responses were even seen in three patients with hepatic metastases. The median time to progression was 6.9 months, and the median overall survival was 10.4 months. Two patients who achieved CR status remain free of disease at 4 and 3 years respectively. Grade 3–4 granulocytopenia occurred in 27 patients, resulting in five episodes of febrile neutropenia. There was one toxic death in a patient with grade 4 granulocytopenia who developed acute abdomen. Grade 3–4 thrombocytopenia was rare (one patient). Other grade 3–4 toxicities observed were anaemia (three patients), vomiting (five patients), diarrhoea (four patients), peripheral neuropathy (two patients) and non-neutropenic infections (seven patients). Docetaxel plus cisplatin is an effective and well-tolerated regimen for the treatment of advanced urothelial cancer, and warrants further investigation

Risk of ischaemic heart disease and acute myocardial infarction in a Spanish population: observational prospective study in a primary-care setting

BACKGROUND: Ischaemic heart disease is a global priority of health-care policy, because of its social repercussions and its impact on the health-care system. Yet there is little information on coronary morbidity in Spain and on the effect of the principal risk factors on risk of coronary heart disease. The objective of this study is to describe the epidemiology of coronary disease (incidence, mortality and its association with cardiovascular risk factors) using the information gathered by primary care practitioners on cardiovascular health of their population. METHODS: A prospective study was designed. Eight primary-care centres participated, each contributing to the constitution of the cohort with the entire population covered by the centre. A total of 6124 men and women aged over 25 years and free of cardiovascular disease agreed to participate and were thus enrolled and followed-up, with all fatal and non-fatal coronary disease episodes being registered during a 5-year period. Repeated measurements were collected on smoking, blood pressure, weight and height, serum total cholesterol, high-density and low-density lipoproteins and fasting glucose. Rates were calculated for acute myocardial infarction and ischaemic heart disease. Associations between cardiovascular risk factors and coronary disease-free survival were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: Mean age at recruitment was 51.6 ± 15, with 24% of patients being over 65. At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers. During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate analyses. After multivariate adjustments, age, male gender, smoking, high total cholesterol, high HDL/LDL ratio, diabetes and overweight remained strongly associated with risk. Relative risks for hypertension in women and for diabetes in men did not reach statistical significance. CONCLUSION: Despite high prevalence of vascular risk factors, incidence rates were lower than those reported for other countries and other periods, but similar to those reported in the few population-based studies in Spain. Effect measures of vascular risk factors were mainly as reported worldwide and support the hypothesis that protective factors not considered in this study must exist as to explain low rates. This study shows the feasibility of conducting epidemiological cohort studies in primary-care settings

Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer

A multicentre phase II trial was undertaken to evaluate the activity and toxicity of docetaxel plus cisplatin as first-line chemotherapy in patients with urothelial cancer. Thirty-eight patients with locally advanced or metastatic transitional-cell carcinoma of the bladder, renal pelvis or ureter received the combination of docetaxel 75 mg m−2 and cisplatin 75 mg m−2 on day 1 and repeated every 21 days, to a maximum of six cycles. The median delivered dose-intensity was 98% (range 79-102%) of the planned dose for both drugs. There were seven complete responses and 15 partial responses, for and overall response rate of 58% (95% CI, 41-74%). Responses were even seen in three patients with hepatic metastases. The median time to progression was 6.9 months, and the median overall survival was 10.4 months. Two patients who achieved CR status remain free of disease at 4 and 3 years respectively. Grade 3-4 granulocytopenia occurred in 27 patients, resulting in five episodes of febrile neutropenia. There was one toxic death in a patient with grade 4 granulocytopenia who developed acute abdomen. Grade 3-4 thrombocytopenia was rare (one patient). Other grade 3-4 toxicities observed were anaemia (three patients), vomiting (five patients), diarrhoea (four patients), peripheral neuropathy (two patients) and non-neutropenic infections (seven patients). Docetaxel plus cisplatin is an effective and well-tolerated regimen for the treatment of advanced urothelial cancer, and warrants further investigation