RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study

BACKGROUND: Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. METHODS: In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. RESULTS: The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. CONCLUSION: Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data

Aligning evidence generation and use across health, development, and environment

© 2019 The Authors Although health, development, and environment challenges are interconnected, evidence remains fractured across sectors due to methodological and conceptual differences in research and practice. Aligned methods are needed to support Sustainable Development Goal advances and similar agendas. The Bridge Collaborative, an emergent research-practice collaboration, presents principles and recommendations that help harmonize methods for evidence generation and use. Recommendations were generated in the context of designing and evaluating evidence of impact for interventions related to five global challenges (stabilizing the global climate, making food production sustainable, decreasing air pollution and respiratory disease, improving sanitation and water security, and solving hunger and malnutrition) and serve as a starting point for further iteration and testing in a broader set of contexts and disciplines. We adopted six principles and emphasize three methodological recommendations: (1) creation of compatible results chains, (2) consideration of all relevant types of evidence, and (3) evaluation of strength of evidence using a unified rubric. We provide detailed suggestions for how these recommendations can be applied in practice, streamlining efforts to apply multi-objective approaches and/or synthesize evidence in multidisciplinary or transdisciplinary teams. These recommendations advance the necessary process of reconciling existing evidence standards in health, development, and environment, and initiate a common basis for integrated evidence generation and use in research, practice, and policy design