Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group.

PURPOSE: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study. PATIENTS AND METHODS: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior. RESULTS: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B. CONCLUSION: The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.     

MET receptor is a potential therapeutic target in high grade cervical cancer

Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype.Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma.     

Estudio de intervención formativa con miniensayos para mejorar la atención de las urgencias médicas en un centro de salud

ObjectiveTest effectiveness and acceptability of interventions short essay-type training in health emergency management (EM).DesignCombined case series and controlled study before and after training sessions.LocationHealth Center (HC).ParticipantsTeam on duty, two monitors-facilitators, and a mannequin.Main measuresVariables: response times, staff performance, resource usage and opinion. Structure: scenarios and key messages. Instrument development: 1. Initial/final questionnaire and events. 2. Essential/non-essential times; 3. Post-test opinion questionnaire. Performance of six consecutive 15 min tests fortnightly (including corrections) and poll after each test. A month later, repeat in random order and under similar conditions. Analysis: repeated measures.ResultsA total of 93 (2/3) workers completed the initial survey, and 74 the final, with 46 participants (25 doctors, 7 nurses, 21 non-health completed 95 direct interventions. Matching participants > 80% between series. A reduction was seen in the “detection of collapse to first defibrillation” interval (10 to 4 min). EM events improved 2-3 fold and “sense of security during a real EM” increased from 23% to 71% among participants. The vast majority of participants said “useful corrections made by the facilitator.” The proportions of those who “would like to see tests introduced” and those who said “re-training was needed in EM” were moderately increased (67.4% vs 85% in health care workers). The “would like to attempt basic life support” was unchanged.ConclusionDespite being reduced in number and duration, this model of intervention has shown positive trends in terms of use and acceptability for implementation in the HC.