Atenolol vs enalapril in young hypertensive patients after successful repair of aortic coarctation.

Late arterial hypertension has been identified as a major predictor for morbidity and mortality in aortic coarctation (AoC) patients. Few data are available about efficacy and tolerability of angiotensin converting enzyme inhibitors vs beta-blockers in young AoC patients. This study aimed to evaluate the tolerability and efficacy on 24-h blood pressure (BP) and left ventricular mass/height(2.7) (LVMI), of atenolol vs enalapril. We enrolled consecutive AoC hypertensive patients with (a) no history of BP treatment or after >48 h of withdrawn, (b) aged 6-20 years, (c) body mass index (BMI) <90th percentile for age and sex, (d) >12 months from a successful AoC repair and (e) no major associated cardiovascular abnormalities. All patient were evaluated with 24-h ambulatory BP monitoring, standard echocardiography, strain-strain rate imaging, at enrolment, 3, 6 and 12 months of treatment. We studied 51 AoC patients (13±3.9 years, BMI: 21.4±4.3 kg m(-2)). Patients were randomly assigned at atenolol treatment (n=26), or enalapril treatment (n=25). The mean follow-up duration was 11±2 months. Both drugs were able to significantly reduce 24-systolic BP (SBP; atenolol: 133±11 mm Hg vs 124±16 mm Hg, P=0.016; enalapril: 135±6 mm Hg vs 127±7 mm Hg, P=0.001). Only enalapril was able to significantly reduce LVMI (47±12 vs 39.6±10 g m(-)(2.7), P=0.016). Only in atenolol group in two cases (7.7%) drug withdrawal was needed because of adverse events. Enalapril and atenolol are similarly effective in reducing SBP. However, only enalapril demonstrated a significant reduction of LVMI. In no case, enalapril was stopped because of adverse events.

Masked hypertension in young patients after successful aortic coarctation repair: impact on left ventricular geometry and function.

Life expectancy is still reduced in aortic coarctation (AoC) patients despite a successful repair because of late arterial hypertension and atherosclerosis. Masked hypertension (MH) consists of an elevated daytime or awake ambulatory blood pressure (BP) in the presence of a normal BP on conventional measurement at the office. To assess the prevalence of MH among AoC normotensive young patients successfully treated and to evaluate the impact of MH on left ventricular (LV) geometry and function.We studied 76 AoC patients (mean age 14.5±5.7 years, male 64%). According to 24 h ambulatory BP monitoring (ABPM) our sample was divided in real normotensive patients (Group RN, n=40) and MH patients (Group MH, n=36). There was an increased pressure gradient in the aortic arch (15 mm Hg±4 vs 13 mm Hg±4.7, P<0.05), increased LV mass (51 g m(-2.7)±13 vs 46 g m(-2.7)±12, P<0.05), in MH AoC patients. Regional longitudinal deformation properties of the basal septal segment (-15%±2.4 vs -20%±5, P<0.01) and LV twist values (14°±1.6 vs 12°±1.9, P<0.0001) were reduced in the MH group. There is a high prevalence of MH in young patients with repaired AoC, which is associated with abnormal LV structure and function. Clinicians should consider 24 h ABPM measurements in apparently normotensive patients followed up for AoC repair.

Chemotherapy of advanced NSCLC in special patient population.

The elderly and patients with Performance Status (PS) of 2, constitute the so-called special patient population. The tolerability of chemotherapy in this population is globally worse, and treatment approaches should be different. Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its role in special patient population is controversial. The best treatment for elderly patients with advanced NSCLC is still debated. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. However, the role of platin-based chemotherapy needs to be defined in prospective randomised trials. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, taxanes) should be the recommended option for non-selected elderly patients with advanced NSCLC. Also for PS2 patients there is no consensus on standard treatment. On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations and role of new targeted therapies.

Italian clinical research in non-small-cell lung cancer.

Lung cancer is the most common cause of cancer deaths in both men and women worldwide and has a poor prognosis. Non-small-cell lung cancer (NSCLC) represents approximately 80% of all lung cancers. Surgery is the only curative treatment of NSCLC but only 15-20% of tumours can be radically resected with a survival of about 40% at 5 years. Considering these disappointing results NSCLC is one of the most frequent subjects of clinical research worldwide. Italy is playing an important role in the clinical research of NSCLC performing phase I, II and III trials, prevalently by cooperative groups, and achieving important results that contributed to define the standard treatment for NSCLC patients. In particular, Italy is leader in the clinical research of the treatment of advanced NSCLC elderly patients. Today, large controlled clinical trials are ongoing. In this paper we analyse and discuss the main trials performed by Italian groups in the fields of NSCLC.

Addition of either irinotecan or methotrexate to bolus 5-fluorouracil and high-dose folinic acid every 2 weeks in advanced colorectal carcinoma: a randomised study by the Southern Italy Cooperative Oncology Group.

PURPOSE: The purpose of this study was to compare the activity and toxicity of the combination of irinotecan (IRI) plus folinic acid (FA)-modulated 5-fluorouracil (5-FU) i.v. bolus with a regimen of double modulation of 5-FU with methotrexate (MTX) and FA in patients with advanced colorectal carcinoma. PATIENTS AND METHODS: Two-hundred and thirty-four patients were enrolled: 118 patients received IRI 200 mg/m2 (90-min i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and 5-FU 850 mg/m2 (i.v. bolus) on day 2 (IRIFAFU), and 116 patients received MTX 750 mg/m2 (2-h i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and FU 800 mg/m2 (i.v. bolus) on day 2 (MTXFAFU). Both cycles were repeated every 2 weeks until progression or to a maximum of 16 cycles. Response rate (RR) was the main end point of the study; responses were assessed every four cycles and confirmed after 2 additional months of treatment. RESULTS: RR was significantly greater with IRIFAFU (36%) than with MTXFAFU (20%) (P <0.001). Multivariate analysis showed that IRIFAFU was significantly associated with a greater activity (P = 0.028). Median progression-free survival was longer with IRIFAFU than with MTXFAFU (7.2 months compared with 4.8 months; P = 0.048). Median survival time (MST) did not differ between the two arms (14.7 months compared with 14.8 months, respectively). Patients not receiving second-line chemotherapy, however, lived longer when treated in the first-line with IRIFAFU (MST 11.9 months compared with 6.4 months; P = 0.038). IRIFAFU caused a significantly greater occurrence of grade 3 or 4 neutropenia (40% compared with 9%; P = 0.001) and diarrhoea (13% compared with 4%; P = 0.024), but a significantly lower incidence of stomatitis (3% compared with 12%; P = 0.007), than the comparative regimen. CONCLUSIONS: IRIFAFU appeared comparable in terms of activity and toxicity with other weekly or biweekly bolus or infusional combination regimens. IRIFAFU, however, seems easier to administer, because it does not require infusional catheter or pump devices, and it is less expensive. It may represent a new option for treating advanced colorectal carcinoma.

Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia.

The toxicity and therapeutic activity, including the effect on quality of life, of the carboplatin-oral etoposide combination, given with an intrapatient dose escalation, was tested in 38 non-small cell lung cancer (NSCLC) patients aged over 70 years, and in 8 younger patients with a performance status of 2. In the absence of grade 3-4 toxicity, doses were escalated as follows: first course (carboplatin AUC 4; etoposide 50 mg twice daily orally days 1-14); second course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-14); third course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-21). A total of 141 chemotherapy cycles were delivered. The treatment was, in general, well tolerated and no toxic deaths occurred. More than 60% of patients received 100% of the planned dose intensity. Transient grade 4 neutropenia or thrombocytopenia occurred in 6 and 2 patients, respectively, but only 2 patients had to be hospitalised because of fever. All patients were evaluated for activity on an 'intention to treat basis'. Ten partial responses and 20 stable disease were recorded, for an overall response rate of 22% (95% confidence interval (CI) = 11-36). 9/38 (24%; 95% CI = 12-41) elderly patients obtained a partial response. The median response duration was 4 months. A quality of life improvement was observed in 19 of the 46 enrolled patients (41%; 95% CI = 27-57), and 15/46 (33%; 95% CI = 19-48) showed a performance status improvement. The quality of life score improved in 17/38 (45%) elderly patients. 8/10 responders and 11/20 patients with stable disease showed a concomitant improvement in quality of life. At a median potential follow-up of 16 months (range 2-21), 31 patients had had progression of disease and 23 had died, for a median time to progression (TTP) and overall survival (OS) of 5 and 10 months, respectively. The median survival time was 11 months in the elderly patients. The median time to subjective impairment (TSI) was 6 months (7 months in the elderly group). One-year estimated TTP, TSI and OS rates were 22, 29 and 41%, respectively. At multivariate Cox analysis, a > 25% improvement in the quality of life score was more predictive of a better survival outcome than the response achievement.