Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design (ECTO II).

Sequential doxorubicin/paclitaxel (AT) followed by CMF treatment was shown to be an active neoadjuvant chemotherapy regimen in the first European Cooperative Trial in Operable Breast Cancer (ECTO I trial). The aim of the current study (ECTO II) is to assess the complete pathological response (pCR) rate following three different anthracycline and taxane-containing neoadjuvant chemotherapy regimens, with or without capecitabine (X). Patients with operable, invasive breast cancer > 2.0 cm in diameter, were randomized to AT→CMF, AT→CMX or AC→TX regimens in two parallel, randomized, open-label, phase II trials (within a single study) in patients with estrogen receptor negative (ER-) and estrogen receptor positive (ER+) diseases, respectively. Exemestane was delivered concomitantly with neoadjuvant chemotherapy in ER+ tumors. Achievement of pCR was more common in ER- than ER+ women (45.3 vs. 10.4%). Capecitabine was only associated with a higher frequency of pCR in ER+ patients receiving AT→CMX. Overall response rates (ORR) ranged from 88 to 97%, and this translated into high rates of breast-conserving surgery (67% of ER- patients and 72% of ER+ patients). All three regimens were well tolerated. Febrile neutropenia and gastrointestinal effects were the most common grade ≥ 3 adverse events. As expected, the ECTO II study showed higher pCR rates in patients with ER- disease. Substituting capecitabine for fluorouracil (± methotrexate) in anthracycline/taxane-containing regimens appeared to be beneficial only in ER+ tumors. Translational studies investigating interactions between therapeutic agents and tumor biology are warranted to refine patient selection and improve the results of neoadjuvant chemotherapy.

Cardiac deatH prevention by aUtomated defibrillatoRs in ChurcHes: rationale and design of the CHURCH trial.

Early defibrillation programs by the use of automated external defibrillators (AEDs) located in high-attendance public places may improve survival and neurologic outcome of patients undergoing sudden cardiac arrest (SCA). We planned a prospective cohort study to assess the effectiveness of a public-access defibrillation program based on positioning of AEDs in churches and training of lay volunteers in Basic Life Support Defibrillation during a single-day 5-hour training session. The CHURCH project aims to promote a widespread diffusion of AEDs, to train a large number of lay volunteers in Basic Life Support Defibrillation, and to increase population awareness on the opportunities for sudden death prevention. The rationale of the study rests on a survey commissioned by the Diocese of Milan that found a high prevalence of elderly subjects (44.5% were >60 years old) attending holy services in the morning hours, when sudden death incidence peaks. The catchment areas of the 12 parishes included in the trial as of June 2008 include a population of 140,000. The projected incidence of AED-treatable SCA, based on the presence of trained volunteers in the churches during day hours, at the CHURCH participating sites was estimated at 8 episodes per year. To estimate an overall 30% mortality reduction from SCA after AED placement at the study sites with respect to conventional SCA management by the Emergency Medical Service, 25 SCA episodes will have to be treated during the 4-year study period. The CHURCH project might be of interest and applicable in every country where high-attendance worship places are present.

Peripheral neuropathy due to paclitaxel: study of the temporal relationships between the therapeutic schedule and the clinical quantitative score (QST) and comparison with neurophysiological findings.

Peripheral neuropathy (PN) is one of the most common and dose-limiting side effects of paclitaxel, a chemiotherapeutic drug of proven efficacy in various tumours. We investigated the pathophysiological features of the PN and the temporal relationships between the development of the symptoms and signs associated with paclitaxel administration in two groups of patients with breast cancer: group A received paclitaxel alone (total cumulative dose range: 950-2,475 mg/m2), and group B paclitaxel and adriamycin (total cumulative dose range: 700-2,800 mg/m2). A codified assessment scoring clinical sensory and motor functions according to the Common Toxicity Scale and neurophysiological measurements were made before treatment, after the third and sixth cycles, and at the end of therapy. A total neuropathy score (TNS) included selected clinical and neurophysiological parameters. Both positive and negative sensory and motor symptoms and signs of PN developed during therapy, the most common being painful paresthesias, global areflexia and distal weakness. The neurophysiological study showed an early onset, length-independent and progressive sensory defect, and delayed, distal and length-dependent motor deficits. The neuropathy progressed faster in group A than in group B but, after therapy, most of the patients were TNS grade 2 regardless of their group. The temporal relationships between the PN and paclitaxel were robustly characterised, and thus provide reference data and a model for testing the efficacy of drugs designed to provide neuroprotection.