Search: onr:"swepub:oai:DiVA.org:uu-208545" >
Comparison of Two M...
Comparison of Two Mitotane Starting dose Regimens in Patients with Advanced Adrenocortical Carcinoma
-
Kerkhofs, Tm (author)
-
Baudin, E (author)
-
Terzolo, M (author)
-
show more...
-
Allolio, B (author)
-
Chadarevian, R (author)
-
Mueller, Hh (author)
-
- Skogseid, Britt (author)
- Uppsala universitet,Endokrin tumörbiologi
-
Leboulleux, S (author)
-
Mantero, F (author)
-
Haak, Hr (author)
-
Fassnacht, M (author)
-
show less...
-
(creator_code:org_t)
- The Endocrine Society, 2013
- 2013
- English.
-
In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:12, s. 2281-
- Related links:
-
https://academic.oup...
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Context:Mitotane is the only approved drug for treatment of adrenocortical carcinoma(ACC). Its pharmacokinetic properties are not fully elucidated and different dosing regimens have never been compared head-to-head.Objective:To investigate the relationship between mitotane dose and plasma concentration comparing two dosing regimens.Design/Setting:Prospective open-label multicenter trial of a predefined duration of twelve weeks.Patients/Interventions:Forty mitotane-naïve patients with metastatic ACC were assigned to a predefined low- or high-dose regimen by the local investigator. Thirty-two could be evaluated in detail.Main Outcome Measure:Difference in median mitotane plasma levels between both treatment groups.Results:Despite a difference in mean cumulative dose (440±142g versus 272±121g), median maximum plasma levels were not significantly different between the two groups (high-dose 14.3mg/L (6.3-29.7,n=20) versus 11.3mg/L (5.5-20.0,n=12), p=0.235). Ten out of twenty patients on the high-dose regimen reached plasma concentrations ≥14mg/L after 46 days (18-81 days) compared to four of twelve patients on the low-dose regimen after 55 days (46-74 days,p=0.286). All patients who reached 14mg/L at 12 weeks displayed a level ≥4.1 mg/L on day 33 (100% sensitivity). There were no significant differences in frequency and severity of adverse events. Among patients not receiving concomitant chemotherapy mitotane exposure was higher in the high-dose group: 1013±494mg.d/L versus 555±168mg.d/L, p=0.080.Conclusions:The high-dose starting regimen did neither result in significantly different mitotane levels nor in a different rate of adverse events, but concomitant chemotherapy influenced these results. Thus, for mitotane monotherapy the high-dose approach is favorable, whereas for combination therapy a lower dose seems reasonable.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Kerkhofs, Tm
-
Baudin, E
-
Terzolo, M
-
Allolio, B
-
Chadarevian, R
-
Mueller, Hh
-
show more...
-
Skogseid, Britt
-
Leboulleux, S
-
Mantero, F
-
Haak, Hr
-
Fassnacht, M
-
show less...
- Articles in the publication
-
Journal of Clini ...
- By the university
-
Uppsala University