Patterns of relapse and modalities of treatment of breast cancer: the 'IRIS' Project, a multicenter observational study.

OBJECTIVES: The aim of this study was to describe the patterns of breast cancer relapse and the factors influencing therapeutic choices in an unselected postmenopausal population. METHODS: Five hundred and thirty-nine patients were enrolled between October 1999 and March 2001. The majority (92.6%) underwent surgery for the primary tumor: there was no difference between general and university hospitals in terms of the type of mastectomy, but a slight difference was found between Southern and Northern Centers. RESULTS: At the time of first relapse, 61.6% of the patients had a good Karnofsky performance status. The median disease-free interval (DFI) was 34 months. More than half of the patients (62.3%) presented a single metastasis. Metastatic disease was treated with chemotherapy in 64.8% of cases (alone in 44.1%, and in combination with hormone therapy in 20.1%), hormone therapy alone was given in 30.8% of cases. The main reasons for choosing chemotherapy were age (31%), standard guidelines (19.4%) and the site of metastatic disease (14.3%), and those for selecting hormone therapy were age (26.6%), site of relapse (19.3%), standard guidelines (19.2%), biological tumor characteristics (14.3%) and the DFI (11.1%). Taxane-containing treatments accounted for 46.1% of the chemotherapies, whereas letrozole was the preferred hormone (41.2%). CONCLUSION: The first relapse of breast cancer is often single, at bone or viscera, and mainly diagnosed by instrumental screening examinations. The preferred chemo- and hormone therapies are taxane-containing regimens and letrozole, respectively.

Serious or fatal complications after inadvertent administration of ionic water-soluble contrast media in myelography.

The consequences of the inadvertent administration, by the intrathecal route, of ionic contrast media instead of iopamidol in seven subjects are reported. The ionic compounds were diatrizoate, iodamide and ioxitalamate. The outcome was fatal in three out of seven subjects, and it depended on the type and the dose of the administered contrast agent. The serious or fatal reactions observed are a tragic confirmation of the predictive power of neurotoxicity data obtained in animal studies with various iodinated water-soluble compounds. The margin of safety, represented by the ratio of LD50 i.ce. in mice to clinical dose in humans, both normalized to bodyweight, appears to reliably reflect the risk of toxic reactions after intrathecal administration of iodinated contrast agents.

Iopamidol in cardioangiography: a retrospective, multicenter study. Part I. Adult patients.

To evaluate the occurrence of complications during diagnostic or interventional catheterization a retrospective analysis of catheterization procedures in 12 Italian laboratories using the nonionic contrast medium (CM) iopamidol (370 mgI/ml) was performed. Data obtained on 26,219 patients greater than or equal to 14 years are presented. The overall complication rate was 1.89% (485/26,219). The overall mortality rate was 0.1% (27/26,219). Procedure related complications were 389 (1.48%) and CM related complications were 106 (0.4%). No death was attributed to CM. Ventricular fibrillation (VF) rate was 0.11% comparable to the low rate observed with nonionic CM in other studies and less than the rate observed in surveys concerning the use of ionic CM. Fifty-seven thrombotic events were recorded (0.22%), a rate comparable with other surveys with ionic and nonionic CM. The total complication rate (6.1%), the rates of coronary occlusion (1.34%), myocardial infarction (0.37%) and urgent coronary artery by-pass grafting (0.5%) in 1,348 coronary angioplasties were lower than those recorded in previous surveys. These data confirm a good tolerability and no increased risk of VF and thrombotic events with iopamidol in cardiac catheterization.

Iopamidol in cardioangiography: a retrospective, multicentre study. Part II. Paediatric patients.

To evaluate the complication rate in paediatric cardioangiography with the nonionic contrast medium iopamidol data on 8,166 procedures were retrospectively collected in 12 centres. The overall complication rate was 3.78% (309/8,166). 3.44% were related to the procedure, and 0.34% to the contrast medium. The mortality rate varied with age. It was higher in patients less than 2 months (0.38%) than in patients greater than 2 months-2 years (0.06%) and in patients older than 2 years (0.03%). The total complication rate was higher than the one observed in a similar retrospective analysis performed in adult patients (1.89%). This difference is probably due to higher risk conditions of the younger patients. However the contrast medium related complication rate (0.34% vs 0.4%) and the mortality rate (0.11% vs 0.1%) were comparable, confirming the good tolerability of iopamidol in cardiac catheterisation also in paediatric patients.

Comparison of the new alpha 1-blocker alfuzosin with propranolol as first-line therapy in hypertension.

The new alpha 1-blocker alfuzosin was compared with propranolol as monotherapy for hypertension in a double-blind, parallel group study of 8-week duration in 40 patients with essential hypertension. The patients (11 males, 29 females; mean age 47.8 +/- 2.2 years in the alfuzosin group and 46.6 +/- 2.4 years in the propranolol group) randomly received either alfuzosin from 2.5 mg b.i.d. up to 10 mg b.i.d. or propranolol from 40 mg b.i.d. up to 160 mg b.i.d. according to an individualized dose-titration schedule. The two groups were comparable with respect to disease history, cardiovascular risk factors, concomitant diseases, previous treatments and end-placebo blood pressure and heart rate values. Four patients did not complete the study, two patients in the alfuzosin group: one patient because of postural hypotension and the second one because of breast cancer; and two patients in the propranolol group: one patient for inefficacy and the second one lost to follow-up. At the end of the 8-week trial the mean daily doses were 12.2 +/- 0.61 mg and 196 +/- 9.82 mg for alfuzosin and propranolol, respectively. The antihypertensive effects of the two drugs were comparable. Upright and supine blood pressures decreased significantly with both treatments from the second week on (P less than 0.001 for all BP values). At the end of the 8-week double-blind trial, 83% of alfuzosin patients and 67% of propranolol patients were normalized. The two treatments differed significantly with respect to their effect on heart rate. Alfuzosin did not induce marked changes in heart rate: only a slight increase was observed. In contrast, propranolol caused bradycardia, more marked in the upright position. Palpitations, headache, asthenia and orthostatic hypotension were reported in the alfuzosin group. Asthenia and decreased libido were reported in the propranolol group. These data prove that alfuzosin has antihypertensive effects equivalent to propranolol and it is an interesting agent for the therapy of essential hypertension. It can be used as a first agent at doses between 5 and 20 mg/day with satisfactory therapeutic response and without relevant side-effects.

Intravenous diltiazem in patients with paroxysmal re-entrant supraventricular tachycardia.

The electrophysiologic effects and efficacy of diltiazem were evaluated with programmed electrical stimulation of the heart in 12 patients with supraventricular re-entrant tachycardia (five with atrioventricular nodal tachycardia and seven with circus movement tachycardia the accessory pathway being concealed in 4). Diltiazem was infused over 1 minute at the dose of 0.25 mg/kg and the electrophysiologic parameters were evaluated at 5 and 30 minutes. Diltiazem prolonged the AH interval from 83.5 +/- 58 to 99 +/- 55 msec (P less than 0.05), effective and functional refractory periods of atrioventricular node from 244 +/- 40 to 268 +/- 56 msec (P less than 0.05) and from 432 +/- 124 to 468 +/- 130 msec (P less than 0.005) respectively, lowered the atrial pacing rate inducing second-degree atrioventricular block from 159 +/- 32 to 134 +/- 33 beats/min (P less than 0.005) and decreased systolic and diastolic blood pressure from 143.5 +/- 33 to 132.5 +/- 22 mm Hg (P less than 0.05) and from 90 +/- 15 to 82.5 +/- 9 (P less than 0.05), respectively. Diltiazem prevented the reinduction of the tachycardia in 4 of 5 patients with atrioventricular nodal tachycardia and in 4 of 7 with circus movement tachycardia. The mechanism of action of diltiazem consisted of depression of conduction in atrioventricular node in anterograde fashion while there were no effects on refractoriness of the accessory pathway. The drug was well tolerated with no adverse effects. Diltiazem, therefore, appears an effective and safe drug in the acute treatment of re-entrant supraventricular tachycardia.

Dose-titration study of alfuzosin, a new alpha 1-adrenoceptor blocker, in essential hypertension.

An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was greater than 90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypotensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response relationship of prizidilol hydrochloride (SK&F 92657): a comparison between acute and chronic effects in patients with essential hypertension.

Three different doses (50, 100 and 200 mg) of prizidilol hydrochloride (SK&F 92657), a novel antihypertensive agent with vasodilating and beta-adrenoreceptor blocking properties, were given to three (n = 5) groups of essential hypertensive patients in order to evaluate hypotensive dose-response relationship of the drug and its beta-adrenoreceptor blocking properties. Irrespective of the dose given, acute administration of prizidilol did not effectively decrease blood pressure; however after one-week of treatment prizidilol was effective in reducing blood pressure at both the 100 and the 200 mg b.i.d. schedules. At these doses the drug decreased resting heart rate and plasma renin activity for the first 4-6 h after both acute and steady-state dosing. Similarly postdynamic exercise tachycardia was reduced to a significant extent by the drug; after acute administration this effect lasted 2 h with the lowest dose and 4 h with the highest one. After chronic administration this effect lasted up to 10 h for both the 100 and 200 mg doses. These data indicate that: chronic prizidilol treatment can achieve a satisfactory control of blood pressure in patients with mild-moderate essential hypertension; when prizidilol is administered chronically in hypertensive patients, an equally effective control of blood pressure can be obtained with either a 200 mg b.i.d. or a 100 mg b.i.d. schedule; prizidilol possesses beta-adrenoceptor blocking properties in man which can contribute to its pharmacodynamic activity.