Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109

Embryonic development of four species of palaemonid prawns (Crustacea, Decapoda): pre-naupliar, naupliar and post-naupliar periods

The embryonic development of four species of the family Palaemonidae was studied under laboratory conditions. Adults of Macrobrachium olfersi (Wiegman, 1836), Macrobrachium potiuna (Müller, 1880), Palaemon pandaliformis (Stimpson, 1871) and Palaemonetes argentinus (Nobili, 1901) were collected in Santa Catarina Island, Santa Catarina, Brazil and maintained at 26ºC. The following embryonic characters were analyzed: egg shape, yolk organization and cleavage plane, naupliar and post-naupliar appendages, stomodeum, optical lobes, eyes, telson, embryo curvature and the space occupied by the embryo in the egg. Different rates of development were observed for the four species, with M. potiuna showing the longest time of embryogenesis. The species studied followed the pattern of embryogenesis of centrolecithal eggs, enabling the identification of similar features of the development, and the establishment of eight common embryonic stages.<br>Foi estudado o desenvolvimento embrionário de quatro espécies de Palaemonidae em condições controladas de laboratório. Adultos de Macrobrachium olfersi (Wiegman, 1836), Macrobrachium potiuna (Müller, 1880), Palaemon pandaliformis (Stimpson, 1871) e Palaemonetes argentinus (Nobili, 1901) foram coletados na Ilha de Santa Catarina, SC, Brasil e mantidos à temperatura de 26ºC. Foram analisadas as seguintes características embrionárias: forma do ovo, organização do vitelo e planos de clivagem, apêndices naupliares e pós-naupliares, estomodeo, lobos ópticos, olhos, telson, curvatura do embrião e o espaço ocupado pelo embrião no ovo. Diferentes ritmos de desenvolvimento foram observados espécies, sendo que M. potiuna mostrou o maior tempo de embriogênese. As espécies seguem o padrão de embriogênese de ovos centrolécitos, sendo identificadas características similares do desenvolvimento, possibilitando o estabelecimento de oito estágios embrionários, comuns as quatro espécies