Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial

BACKGROUND: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. METHODS: Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status ≤ 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m(2), every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m(2), every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0. RESULTS: The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34–75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%). CONCLUSION: This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears manageable

Low-Salt Intake Suggestions in Hypertensive Patients Do not Jeopardize Urinary Iodine Excretion

A low-sodium diet is an essential part of the treatment of hypertension. However, some concerns have been raised with regard to the possible reduction of iodine intake during salt restriction. We obtained 24-h urine collections for the evaluation of iodine (UIE) and sodium excretion (UNaV) from 136 hypertensive patients, before and after 9 &plusmn; 1 weeks of a simple low-sodium diet. Body mass index (BMI), blood pressure (BP), and drug consumption (DDD) were recorded. Data are average &plusmn; SEM. Age was 63.6 &plusmn; 1.09 year. BMI was 25.86 &plusmn; 0.40 kg/m2 before the diet and 25.38 &plusmn; 0.37 kg/m2 after the diet (p &lt; 0.05). UNaV decreased from 150.3 &plusmn; 4.01 mEq/24-h to 122.8 &plusmn; 3.92 mEq/24-h (p &lt; 0.001); UIE decreased from 186.1 &plusmn; 7.95 &micro;g/24-h to 175.0 &plusmn; 7.74 &micro;g/24-h (p = NS); both systolic and diastolic BP values decreased (by 6.15 &plusmn; 1.32 mmHg and by 3.75 &plusmn; 0.84 mmHg, respectively, p &lt; 0.001); DDD decreased (&Delta;DDD 0.29 &plusmn; 0.06, p &lt; 0.05). UNaV and UIE were related both before (r = 0.246, p = 0.0040) and after the diet (r = 0.238, p = 0.0050). UNaV and UIE were significantly associated both before and after the diet (p &lt; 0.0001 for both). After salt restriction UIE showed a non-significant decrease remaining in an adequate range. Our dietary suggestions were aimed at avoiding preserved foods, whereas the cautious use of table salt was permitted, an approach which seems safe in terms of iodine intake

Left Ventricular Mass Reduction by a Low-Sodium Diet in Treated Hypertensive Patients

Objective: To evaluate the left ventricular mass (LVM) reduction induced by dietary sodium restriction. Patients and Methods: A simple sodium-restricted diet was advised in 138 treated hypertensives. They had to avoid common salt loads, such as cheese and salt-preserved meat, and were switched from regular to salt-free bread. Blood pressure (BP), 24-h urinary sodium (UNaV) and LVM were recorded at baseline, after 2 months. and after 2years. Results: In 76 patients UNaV decreased in the recommended range after 2 months and remained low at 2 years. In 62 patients UNaV levels decreased after 2 months and then increased back to baseline at 2 years. Initially the two groups did not differ in terms of BP (134.3 &plusmn; 16.10/80.84 &plusmn; 12.23 vs. 134.2 &plusmn; 16.67/81.55 &plusmn; 11.18 mmHg, mean &plusmn; SD), body weight (72.64 &plusmn; 15.17 vs. 73.79 &plusmn; 12.69 kg), UNaV (161.0 &plusmn; 42.22 vs. 158.2 &plusmn; 48.66 mEq/24 h), and LVM index (LVMI; 97.09 &plusmn; 20.42 vs. 97.31 &plusmn; 18.91 g/m2). After 2years. they did not differ in terms of BP (125.3 &plusmn; 10.69/74.97 &plusmn; 7.67 vs. 124.5 &plusmn; 9.95/75.21 &plusmn; 7.64 mmHg) and body weight (71.14 &plusmn; 14.29 vs. 71.50 &plusmn; 11.87 kg). Significant differences were seen for UNaV (97.3 &plusmn; 23.01 vs. 152.6 &plusmn; 49.96 mEq/24 h) and LVMI (86.38 &plusmn; 18.17 vs. 103.1 &plusmn; 21.06 g/m2). Multiple regression analysis: UNaV directly and independently predicted LVMI variations, either as absolute values (R2 = 0.369; &beta; = 0.611; p &lt; 0.001), or changes from baseline to +2years. (R2 = 0.454; &beta; = 0.677; p &lt; 0.001). Systolic BP was a weaker predictor of LVMI (R2 = 0.369; &beta; = 0.168; p = 0.027; R2 = 0.454; &beta; = 0.012; p = 0.890), whereas diastolic BP was not correlated with LVMI. The prevalence of left ventricular hypertrophy decreased (29/76 to 15/76) in the first group while it increased in the less compliant patients (25/62 to 36/62; Chi2p = 0.002). Conclusion: LVM seems linked to sodium consumption in patients already under proper BP control by medications

Sodium Intake and Target Organ Damage in Hypertension-An Update about the Role of a Real Villain

Salt intake is too high for safety nowadays. The main active ion in salt is sodium. The vast majority of scientific evidence points out the importance of sodium restriction for decreasing cardiovascular risk. International Guidelines recommend a large reduction in sodium consumption to help reduce blood pressure, organ damage, and cardiovascular risk. Regulatory authorities across the globe suggest a general restriction of sodium intake to prevent cardiovascular diseases. In spite of this seemingly unanimous consensus, some researchers claim to have evidence of the unhealthy effects of a reduction of sodium intake, and have data to support their claims. Evidence is against dissenting scientists, because prospective, observational, and basic research studies indicate that sodium is the real villain: actual sodium consumption around the globe is far higher than the safe range. Sodium intake is directly related to increased blood pressure, and independently to the enlargement of cardiac mass, with a possible independent role in inducing left ventricular hypertrophy. This may represent the basis of myocardial ischemia, congestive heart failure, and cardiac mortality. Although debated, a high sodium intake may induce initial renal damage and progression in both hypertensive and normotensive subjects. Conversely, there is general agreement about the adverse role of sodium in cerebrovascular disease. These factors point to the possible main role of sodium intake in target organ damage and cardiovascular events including mortality. This review will endeavor to outline the existing evidence

Simple dietary advice reduces 24-hour urinary sodium excretion, blood pressure, and drug consumption in hypertensive patients

Sodium intake should be restricted to 100 mEq, that is, about 2.3 grams per day. Strict diets, however, are often cumbersome and seldom matched by rigorous compliance. We studied 291 patients on antihypertensive treatment, 240 of whom were instructed to avoid salty foods, such as cheese and cured meats, and to switch from regular bread to salt-free bread. The remaining 51 matched patients constituted a control group and received only generic dietary advice. Na[U]/24h, K[U]/24h, and office BP (automated repeated measurements) were recorded before dieting started and after 9 \ub1 1 weeks of dieting. Our intervention group showed a significant decrease in body weight (71.75 \ub1 14.0 to 70.54 \ub1 13.33 kg, P &lt;.0001), sodium excretion (153.1 \ub1 44.61 to 133.5 \ub1 37.1 mEq/24h, P &lt;.05), systolic and diastolic BP (134.16 \ub1 16.0 to 126.5 \ub1 10.53 mm Hg, P =.014 and 80.59 \ub1 11.47 to 75.9 \ub1 8.72 mm Hg, P =.026, respectively), and drug consumption (1.71 \ub1 0.91 to 1.49 \ub1 0.84 DDD, P &lt;.05). The rate of responders to antihypertensive therapy increased (51.4% to 79.5%). In the control group neither significant nor substantial changes were seen. Our data suggest that even a minimal reduction in the apparent sodium intake ( 3c0.5 grams per day) can improve both BP values and responder rates in treated hypertensive patients, while reducing the consumption of antihypertensive drugs

P-301: Common carotid wall thickening and ambulatory blood pressure monitoring in hypertensive patients

Recently, intima-media thickness (IMT) of carotid artery has received an increasing attention as risk factor for cardiovascular disease. In fact, it has been reported that IMT increase of carotid arteries is directly associated with an increased risk of myocardial infarction and stroke. The increase of IMT is often found in patients with classical vascular risk factors, but its relationships with them are not fully elucidated. From a series of 119 consecutive hypertensive patients who underwent Ambulatory Blood Pressure Monitoring (ABPM), (78 treated, 41 untreated; 57 men, 62 women, mean age 55 \ub1 11, mean Body Mass Index (BMI) 25 \ub1 3), 95 patients without arterial plaque (IMT>1.2mm) were enrolled. All patients were free of cardiovascular, cerebral, renal and metabolic disorders, including diabetes mellitus. 34 patients were mild hypercholesterolemic (<300md/dl), 13 patients regularly smoked more than 10 cig./daily and 4 were former smokers. ABPM was recorded by SpaceLabs 90207 monitor starting at 10 AM, patients being instructed to go to bed at 11 PM and to stand-up at 7 AM. Readings were obtained automatically at 15-min intervals between 7 AM and 11 PM and at 20-min intervals between 11 PM and 7 AM. Within 1 week from ABPM, patients underwent Duplex scanning of neck vessels. IMT was measured at the last centimetre of the Common Carotid Artery (CCA) before the bifurcation. On each side, IMT was measured at three levels (10mm, 5mm before bifurcation and just before bifurcation) at the anterior and lateral projections, thus obtaining 6 measures on each side. Multiple Regression Analysis was performed with SPSS software; nine variables for blood pressure (mean systolic, diastolic, and pulse pressure (PP) during the day, the night, and over 24 hours, respectively) and one variable for IMT, the mean of 12 measures of both CCA, were considered. IMT was significantly related to age (<.00005) and to PP of 24-hours (<.0005). Our data showed that, in a group of hypertensive patients without arterial plaque and associated clinical conditions, the best predictors for carotid thickening were age and PP of 24 hours in this order