Results
pulmonary embolism, death, liver toxicity, Adrenal Tumors, gastrointestinal toxicity, adrenal insufficiency, deaths, neurological toxicity, Cancer
PULMONARY EMBOLISM, ADVERSE EVENT, RECURRENCE, ADRENAL INSUFFICIENCY, ADVERSE EVENTS, ADVERSE EVENT, DISEASE, ADRENAL TUMOR, EVENT, EVENTS, CANCER
From Oct 23, 2008, to Dec 27, 2018, 45 patients were randomly assigned to receive mitotane treatment and 46 to surveillance alone (Trial profileBaseline characteristics in the intention-to-treat populationData are n (%), median (IQR), or n/N (%). ENS@T=European Network for the Study of Adrenal Tumors.Hormone secretion confirmed by laboratory data.Between Jan 4, 2011, and Dec 16, 2018, 95 patients were included in the ADIUVO Observational study, of whom 42 received mitotane and 53 underwent surveillance alone (Among the 91 patients in the ADIUVO trial, disease recurrence occurred in 18 (20%) patients: seven (16%) of 45 in the mitotane group and 11 (24%) of 46 in the surveillance group. One death for pulmonary embolism in a patient free of disease was counted as an additional event in the mitotane group (Efficacy in the intention-to-treat populationData are n (%) and mean (SD) unless otherwise stated.Data are restricted mean survival time and 95% CI, since the median survival was not reached. Difference between groups is 5·52 months (95% CI −10·41 to 21·45).Assessed in 20 patients in the mitotane group and 18 patients in the surveillance group with the QLQ-C30 questionnaire.Assessed in 18 patients in the mitotane group and 15 patients in the surveillance group with the QLQ-C30 questionnaire.Survival in the intention-to-treat populationKaplan-Meier estimates of recurrence-free-survival (A) and overall survival (B).Subgroup analyses of the risk of recurrence at 5 yearsError bars indicate the 95% CI for ln HR. ENS@T=European Network for the Study of Adrenal Tumors. HR=hazard ratio.In the ADIUVO Observational study, disease recurrence occurred in 17 (18%) of 95 patients, with eight (19%) in the mitotane group and nine (17%) in the surveillance alone group. Median recurrence-free survival was not reached (95% CI not reached–not reached), and the median follow-up time for recurrence-free survival was 34 months (IQR 16–67; Seven (8%) of 91 patients died in the ADIUVO trial, with five deaths caused by progressive disease (one in the mitotane group and four in the surveillance group). Median overall survival was not reached (95% CI not-reached–not reached), and the median follow-up time for overall survival was 55 months (IQR 29–73). The rate of 5-year overall survival was 95% (95% CI 89–100) in the mitotane group and 86% (74–100) in the surveillance group (HR 0·46 [95% CI 0·08–1·92]; In the ADIUVO Observational study, death was documented in three patients in the mitotane group and three patients in the surveillance group. The IPW-adjusted 5-year overall survival rate was 86% (95% CI 72–100) in the mitotane group and 90% (79–100) in the surveillance group (The QLQ-C30 questionnaire was completed by 20 (44%) of 45 patients in the mitotane group and 18 (39%) of 46 patients in the surveillance group at baseline, and by 18 (40%) patients in the mitotane group and 15 (33%) patients in the surveillance group at the 6-month evaluation. The scores of the functional scale, symptoms scale, global health status scale of the QLQ-C30 questionnaire were similar at baseline between patients receiving mitotane or active surveillance. Changes from baseline were apparent only in patients receiving mitotane, who experienced a decrease in the scores of the functional scale and global health scale with an increase in the score of the symptoms scale (There were no treatment-related deaths. All patients receiving mitotane reported adverse events that emerged during treatment or worsened as compared with the pre-treatment state. Adverse events in the 42 patients who received mitotaneAdverse events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0). Multiple side-effects were reported by individual patients. Eight patients discontinued prematurely treatment because of grade 3 liver toxicity (three), grade 3 neurological toxicity (two), grade 3 gastrointestinal toxicity (two) and grade 3 haematological toxicity (one). Neurological symptom and adrenal insufficiency were considered as adverse events of special interest.