36066210
First-line therapy for ovarian cancer with carboplatin followed by paclitaxel-gemcitabine (SCOTROC5): a feasibility study and comparative analysis of the SCOTROC series.
BACKGROUND
We have conducted a series of four feasibility studies in stage Ic-IV ovarian cancer exploring six sequential first-line schedules with the same entry criteria in a total of 339 patients. Here we present the results of the sixth study, and an analysis of the overall series.


METHODS
In this trial patients received 4 cycles of carboplatin AUC 7 every 3 weeks, followed by 4 cycles of concurrent paclitaxel 175 mg/m(2) (day 1) and gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks. The primary end-point of the trial was feasibility of administering all cycles of planned chemotherapy to >60% of patients.


RESULTS
Fifty-four patients were recruited to the trial between June 05 and June 06. A total of 40 (74.1%) patients received all 8 cycles of treatment. Reasons for early discontinuation included toxicity (n=8) and disease progression (n=4). The overall response rate was 73.7%, and the median progression free survival (PFS) was 14.2 months with a median follow-up of 24 months. A comparative analysis of all six regimens from the SCOTROC series suggests that the sequential schedule in which paclitaxel was given weekly (median PFS 19.5m) is most effective.


CONCLUSION
The sequential schedule explored in this trial is feasible, but comparative efficacy analysis suggests that trials involving weekly paclitaxel should be prioritised for further study.
8134220
Prognostic factors in ovarian cancer: how close are we to a complete picture?
Prognostic factors in ovarian cancer: how close are we to a complete picture? Ovarian cancer is the fourth most common cause of cancer-related death in women, but is the most lethal of the gynaeco-logical malignancies with 30–40% overall survival at 5 years [1]. This is in part because the majority of patients with ova-rian cancer present with advanced disease, and treatment options at presentation are confined to a combination of debulking surgery and platinum based chemotherapy, which are only partially effective [2]. Consequently, almost all patients with advanced disease ultimately relapse and die of their disease. Advances in the management of these patients are therefore urgently required. Prognostic factors are defined as phenotypes which correlate with overall survival. In general prognostic factors reflect the intrinsic biology of a tumour (e.g. histological subtype, grade), disease extent (e.g. stage) and/or the capacity of a patient to cope with the morbidity associated with the tumour and treatment (e.g. performance status). As well as these pretreatment factors, others which may impact on outcome include the treatment received by a patient (e.g. optimal surgical cytore-duction, platinum-based chemotherapy), and the effect of treatment on the tumour (e.g. complete response) or the patient (e.g. myelosuppression). As clinical tools, prognostic factors can potentially help in individualising treatment for patients. In properly staged early disease (stage Ia/b), patients have a better prognosis and the benefits of adjuvant chemotherapy may be confined to those with adverse features (e.g. histological subtype or grade) [3]. In this context a prognostic factor with a good positive or negative predictive value for individual patients, would be useful in deciding which patients should receive chemotherapy and those for whom the toxicity was not justified. In contrast, in advanced disease, the majority of patients benefit from paclitaxel –carboplatin chemotherapy and debulking surgery. As there are no established alternatives for patients with either good or poor prognosis, pretreatment prognostic stratification has little influence on clinical management [2]. Instead, pre-treatment markers predictive of response or resistance to individual cytotoxic drugs would be more useful in this context for treatment selection. As research tools, prognostic factors can help identify subgroups of patients with especially poor prognosis and alert us to the need to develop alternative treatment strategies for these patients, while in clinical trials prognostic factors are used to balance patients between treatment arms to minimise the risk of confounding. Prognostic factor studies can also provide useful insights into …
26099246
Expression profiling and individualisation of treatment for ovarian cancer.
Ovarian cancer is the commonest cause of gynaecological cancer-related mortality. Patients with this disease generally undergo surgery followed by platinum-taxane chemotherapy, with additional chemotherapy at relapse. Although the prognosis for patients with advanced cancer is poor--a five-year survival of only 30-40%--there is a wide range of outcomes for individual patients. To date, clinico-pathological variables such as age, stage, grade, histology, debulking status and response to chemotherapy continue to provide the basis on which treatment decisions are made for individual patients. Immunohistochemical markers and information on p53 mutation status have been extensively evaluated in ovarian cancer, but have not yet been shown to be sufficiently informative to influence clinical decisions on a routine basis. The recent advent of expression profiling has provided a new impetus to identifying clinically useful prognostic markers. The ambition of personalised medicine through microarray-based profiling appears to be realistic, but further studies on large uniform cohorts are needed before this potential is fully realised.
40070884
Relative plasma volume monitoring for identifying volume-sensitive and -resistant hypertension.
The measurement and management of volume state among long-term dialysis patients has not received much attention. Recent reports suggest that relative plasma volume monitoring may be useful in identifying patients who have volume excess. Among patients who have evidence of excess volume by relative plasma volume monitoring, excess volume removal leads to improvement in interdialytic ambulatory blood pressure. Implementation of this technique can result in improved classification of patients into volume-sensitive and -resistant categories and therefore improve the management of hypertension.
14241795
Role of inhaled corticosteroids in the management of serological allergic bronchopulmonary aspergillosis (ABPA).
BACKGROUND AND AIM
The treatment of choice for allergic bronchopulmonary aspergillosis (ABPA) is oral corticosteroids (OCS). However, they are associated with numerous adverse effects. Inhaled corticosteroids (ICS) are associated with fewer side-effects; however, their role in the management of ABPA remains controversial. In this retrospective study, we evaluate the role of high doses of ICS in serological ABPA (ABPA-S).


METHODS
Patients with ABPA-S were treated with a combination of formoterol/budesonide (24-1600 micrograms per day), and followed up with history, physical examination, chest radiograph and total IgE levels at 6, 12, 18 and 24 weeks. Asthma control was evaluated using the Global Initiative for Asthma (GINA) criteria. OCS were initiated if the IgE levels continued to rise after six months of therapy with ICS.


RESULTS
There were 8 men and 13 women with a mean (SD) age of 39.3 (12.9) years. There was subjective improvement in all patients treated with ICS but none had complete control of asthma. After six months of therapy with ICS, the median IgE levels increased by 99.3%. After the initiation of OCS, there was complete resolution of asthma symptoms in 19 patients, and IgE levels fell by a median of 52.6% at six weeks. The median duration of follow-up was 15 months after OCS therapy. Eighteen patients achieved complete remission and three patients had a relapse in the first three months after stopping OCS. One patient required long-term OCS and was classified as glucocorticoid-dependent ABPA.


CONCLUSION
High doses of ICS alone have no role in the management of ABPA-S and should not be used as first-line therapy. In patients receiving OCS or alternate therapy, ICS can be used as an add-on therapy for the control of symptoms of asthma.
24550143
Serologic allergic bronchopulmonary aspergillosis (ABPA-S): long-term outcomes.
BACKGROUND AND AIM
ABPA is radiologically classified on the presence or absence of central bronchiectasis (CB) as ABPA-CB and serologic ABPA (ABPA-S) respectively. Few studies have described the follow-up of patients with ABPA-S. The aim of this retrospective study was to describe the outcomes of ABPA-S.


METHODS
Patients were diagnosed as ABPA-S if they met all the following criteria: asthma, immediate cutaneous hyperreactivity to Aspergillus fumigatus antigen, total IgE levels >1000 IU/mL, A. fumigatus specific IgE levels >0.35 kUA/L and normal HRCT of the chest. They were treated with glucocorticoids and followed up with history, physical examination, chest radiograph and total IgE levels every 6 weeks to 3 months. In addition, an annual spirometry and a biennial HRCT chest were performed in all patients.


RESULTS
Of the 55 patients with ABPA-S, 41 (17 men, 24 women; mean age, 38.3 years) consented for performance of repeat HRCT scans. The median duration of asthma prior to diagnosis of ABPA was six years. The duration of follow-up ranged from 24 to 77 months with the mean (SD) follow-up duration being 43.7 (10.1) months. There was improvement in FEV(1) but not the FVC values during the follow-up period (p values = 0.001 and 0.5 for FEV(1) and FVC respectively). There was no development of CB in any patient. Sixteen patients had a relapse during the follow-up period, and six patients were classified as glucocorticoid-dependent ABPA.


CONCLUSIONS
Although relapses are frequently seen, the long-term outcome of ABPA-S is good with no patient developing CB.
2817123
Physical activity and hemodynamic reactivity in chronic kidney disease.
BACKGROUND AND OBJECTIVES
Patients with chronic kidney disease (CKD) have an elevated cardiovascular risk. This study was designed to understand better the presence and strength of the relationship between physical activity and BP and to explore determinants of hemodynamic reactivity.


DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Twenty-four patients with CKD (mean age 69.5 yr; 3.1 antihypertensive drugs; estimated GFR 47 ml/min per 1.73 m(2), albumin/creatinine ratio 403 mg/g) were studied on three occasions during a 6-wk period with 24-h ambulatory BP monitoring and simultaneous activity monitoring with wrist actigraphy.


RESULTS
Nondippers were found have a greater level of sleep activity compared with dippers, although the awake activity level was similar (7.06 versus 6.73) between groups (P = 0.042 for interaction). In 3587 BP activity pairs, hemodynamic reactivity was variable between individuals (systolic BP reactivity 1.06 [SD 10.50]; diastolic BP reactivity 0.89 [SD 7.80] heart rate reactivity 1.18 [SD 11.00]); those who were more sedentary had a greater increment in systolic BP compared with those who were less sedentary. Antihypertensive drugs blunted hemodynamic reactivity. Hemodynamic reactivity was greatest between 12 a.m. and 8 a.m., making this a vulnerable period for cardiovascular events.


CONCLUSIONS
Greater hemodynamic reactivity in sedentary people with CKD offers a possible and thus far unrecognized mechanism of cardiovascular damage. Besides reducing BP, antihypertensive drugs reduce hemodynamic reactivity, which offers another plausible mechanism of cardiovascular protection with their use.
6267711
Allergic bronchopulmonary aspergillosis in asthma: epidemiological, clinical and therapeutic issues.
Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder caused by immunologic reactions to antigens released by Aspergillus fumigatus, a ubiquitous fungi colonizing the tracheobronchial tree of asthmatic patients. The clinical presentation is usually poorly controlled asthma, recurrent pulmonary opacities and bronchiectasis. The prevalence of ABPA in asthma clinics may be as high as 13% with a global burden of almost 5 million patients. A. fumigatus-specific IgE level is the most sensitive test in diagnosis of ABPA, and all asthmatic patients should be routinely screened with A. fumigatus-specific IgE levels for early diagnosis. The goals of managing ABPA include control of asthma, prevention and treatment of acute exacerbations, and preventing the development or progression of bronchiectasis. Glucocorticoids are the treatment of choice with itraconazole reserved for those with recurrent exacerbations and glucocorticoid-dependent disease. There is a dire need for newer treatment approaches including oral antifungal agents and immunomodulatory therapy.