Abstract 607P
Background
Monitoring of plasma mitotane levels is recommended, but its early prognostic value is unknown and its positive predictive value is low. The objective of this prospective study of the French ENDOCAN-COMETE network was to investigate the prognostic role of: 1/ early total plasma mitotane level (TM) during the first 3 months after initiation (initiation period) and 2/ plasma mitotane levels free (FM) or bound lipoprotein fractions (BM) (MITOLIPO period) during 6 consecutive months.
Methods
Lipoprotein fractions were isolated by ultracentrifugation and mitotane level was determined by HPLC-UV. During the MITOLIPO period, TM, FM and BM were performed every 2 months for 6 months; with a clinical and morphological assessment. The primary endpoint was overall survival from initiation of mitotane and the secondary endpoints were disease control rate at 6 and 12 months according to RECIST 1.1. The relationship between total plasma mitotane and survival was modelled according to different mathematical model.
Results
21 patients with metastatic adrenocortical carcinoma and at least 2 measurements of Mitotane level during the MITOLIPO period were included and followed up for a median of 23 months; a median of 4 (2-8) TM and 3 (2-4) FM and BM measurements, were measured per patient. 12% (±7%) of Mitotane remains free, with little variation over time or from one patient to another. In univariate analysis, the first TM measured at one month (p: 0.047, HR: 0.95, CI95%: 0.86-1), the mean TM (p: 0.082, HR: 0.94, IC95%: 0.88-1.02), the area under the curve (p: 0.089, HR: 0.9, IC95%: 0.99-1) and the mitotane speed of rise on the first 2 samples (p: 0.082, HR: 0.9, IC95%: 0.8-1.2) were correlated to overall survival (23 months). The quadratic model described the best relationship between the first TM and survival, identifying a minimum "effective" threshold of 10-15mg/L with no individualized maximum value. FM was not significantly correlated to overall survival.
Conclusions
This prospective study demonstrates the early prognostic value of TM level measured within the first 3 months of follow-up. No prognostic value of FM was found.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Eric Baudin.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.