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.

The phase diagram and hidden order for generalized spin ladders.

We investigate the phase diagram of antiferromagnetic spin ladders with additional exchange interactions on diagonal bonds by variational and numerical methods. These generalized spin ladders interpolate smoothly between the [Formula: see text] chain with competing nn and nnn interactions, the [Formula: see text] chain with alternating exchange and the antiferromagnetic (AF) S = 1 chain. The Majumdar - Ghosh ground states are formulated as matrix product states and are shown to exhibit the same type of hidden order as the AF S = 1 chain. Generalized matrix product states are used for a variational calculation of the ground state energy and the spin and string correlation functions. Numerical (Lanczos) calculations of the energies of the ground state and of the low-lying excited states are performed, and compare reasonably with the variational approach. Our results support the hypothesis that the dimer and Majumdar - Ghosh points are in the same phase as the AF S = 1 chain.