Decreased dose density of standard chemotherapy does not compromise survival for ovarian cancer patients.

For women diagnosed with ovarian cancer, the standard practice of surgery followed by adjuvant platinum-taxane combination chemotherapy, with cycles administered every 3 weeks, is based on randomized control trials. However, a substantial number of patients require delays or reductions on this schedule. The Cancer Centre of Southeastern Ontario (CCSEO) has historically administered chemotherapy every 4 weeks. We analyzed survival outcomes of our cohort. All ovarian cancer patients treated with chemotherapy at the CCSEO from 1995 to end-2002 were included in this study. Overall survival and progression-free survival were calculated from initiation of chemotherapy using the Kaplan-Meier technique and log-rank tests. Cox regression analysis was used to adjust for age and disease stage. A total of 171 patients were treated with chemotherapy (cisplatin-paclitaxel or carboplatin-paclitaxel), of which 144 received chemotherapy every 4 weeks and 27 every 3 weeks. Median progression-free survival was 19.2 months for the group treated every 4 weeks vs 13.2 months for the 3-weekly group. Median overall survival was 36.5 months compared to 27.1 months, respectively. Trends favored treatment every 4 weeks. In early-stage disease, 5-year overall survival was 74% and 5-year progression-free survival was 68%. Administration of platinum-paclitaxel chemotherapy every 4 weeks did not reduce survival of ovarian cancer patients. Importantly, median survival is favorable compared to results from landmark trials where patients were treated every 3 weeks. These results suggest that decreasing the frequency of chemotherapy cycles does not decrease survival. Prospective trials would be required to compare quality of life and cost-effectiveness.

Crystallization and preliminary X-ray diffraction analysis of antigen-binding fragments which are specific for antigenic conformations of sialic acid homopolymers.

Meningococcal meningitis is a severe childhood disease which often results in significant disability or death. Two major etiological agents of meningitis are the group B meningococci and capsular type K1 E. coli. The virulence of these organisms is attributable to structural mimicry between their common alpha(2-8)-polysialic acid capsular polysaccharide and human tissue antigens, which allows the bacteria to evade immune surveillance. There is currently no effective vaccine to protect against this infection. It has been demonstrated that the capsular polysaccharide of the bacteria can adopt a unique 'antigenic conformation'. This antigenic conformation has formed the basis for the development of an N-propionylated polysialic acid vaccine. Immunization trials in mice with this vaccine show the production of two groups of antibodies, of which only N-propionylated polysialic acid-specific were protective. Knowledge of the structure of the antigen-binding site which recognizes the protective epitope is essential to determining the antigenic conformation of the polysaccharides, and is a critical aspect in understanding and improving the action of potential vaccines. The antigen-binding fragments (Fab) of one protective (13D9) and one non-protective (6B9) monoclonal antibody specific for the capsular polysaccharides of group B meningococci have been crystallized and have undergone preliminary X-ray diffraction analysis. Both crystals are observed to scatter X-rays to approximately 1.7 A resolution at the A1 station at the Cornell High-Energy Synchrotron Source. 13D9 has an orthorhombic unit cell with a = 41.8, b = 102.3, c = 134.7 A, with space group P212121. Fab 6B9 has an orthorhombic unit cell with a = 89.6, b = 132.0 and c = 36.9 A, with space group P21212.