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Tuesday, April 10, 2018

Safety, efficacy and survival of patients with primary malignant brain tumours (PMBT) in phase I (Ph1) trials: the 12-year Royal Marsden experience

Abstract

Background

Primary malignant brain tumours (PMBT) constitute less than 2% of all malignancies and carry a dismal prognosis. Treatment options at relapse are limited. First-in-human solid tumour studies have historically excluded patients with PMBT due to the poor prognosis, concomitant drug interactions and concerns regarding toxicities.

Methods

Retrospective data were collected on clinical and tumour characteristics of patients referred for consideration of Ph1 trials in the Royal Marsden Hospital between June 2004 and August 2016. Survival analyses were performed using the Kaplan–Meier method, Cox proportional hazards model. Chi squared test was used to measure bivariate associations between categorical variables.

Results

100pts with advanced PMBT were referred. At initial consultation, patients had a median ECOG PS 1, median age 48 years (range 18–70); 69% were men, 76% had glioblastoma; 68% were on AEDs, 63% required steroid therapy; median number of prior treatments was two. Median OS for patients treated on a Ph1 trials was 9.3 months (95% CI 5.9–12.9) versus 5.3 months (95% CI 4.1–6.1) for patients that did not proceed with a Ph1 trial, p = 0.0094. Steroid use, poor PS, neutrophil-to-lymphocyte ratio and treatment on a Ph1 trial were shown to independently influence OS.

Conclusions

We report a survival benefit for patients with PMBT treated on Ph1 trials. Toxicity and efficacy outcomes were comparable to the general Ph1 population. In the absence of an internationally recognized standard second line treatment for patients with recurrent PMBT, more Ph1 trials should allow enrolment of patients with refractory PMBT and Ph1 trial participation should be considered at an earlier stage.



from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader https://ift.tt/2qlKLVj

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