Header

UZH-Logo

Maintenance Infos

Mitotane Monotherapy in Patients With Advanced Adrenocortical Carcinoma


Megerle, Felix; Herrmann, Wiebke; Schloetelburg, Wiebke; Ronchi, Cristina L; Pulzer, Alina; Quinkler, Marcus; Beuschlein, Felix; Hahner, Stefanie; Kroiss, Matthias; Fassnacht, Martin; German ACC Study Group (2018). Mitotane Monotherapy in Patients With Advanced Adrenocortical Carcinoma. Journal of Clinical Endocrinology & Metabolism, 103(4):1686-1695.

Abstract

Context Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce. Objective To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors. Design and Setting Multicenter cohort study of three German referral centers. Patients One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy. Outcome Measures Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and predictive factors by Cox regression. Results Twenty-six patients (20.5%) experienced objective response, including three with complete remission. Overall, median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3 to 220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P = 0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS (HR 0.42; P = 0.003). Conclusions At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane and cytotoxic drugs.

Abstract

Context Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce. Objective To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors. Design and Setting Multicenter cohort study of three German referral centers. Patients One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy. Outcome Measures Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and predictive factors by Cox regression. Results Twenty-six patients (20.5%) experienced objective response, including three with complete remission. Overall, median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3 to 220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P = 0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS (HR 0.42; P = 0.003). Conclusions At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane and cytotoxic drugs.

Statistics

Citations

Dimensions.ai Metrics
50 citations in Web of Science®
48 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Endocrinology, Diabetes and Metabolism
Life Sciences > Biochemistry
Life Sciences > Endocrinology
Life Sciences > Clinical Biochemistry
Health Sciences > Biochemistry (medical)
Language:English
Date:1 April 2018
Deposited On:04 Jul 2018 13:05
Last Modified:29 Jul 2020 07:24
Publisher:Endocrine Society
ISSN:0021-972X
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1210/jc.2017-02591
PubMed ID:29452402

Download

Full text not available from this repository.
View at publisher

Get full-text in a library