Comparison of two mitotane starting dose regimens in patients with advanced adrenocortical carcinoma.

Context: Mitotane is the only approved drug for treatment of adrenocortical carcinoma. Its pharmacokinetic properties are not fully elucidated and different dosing regimens have never been compared head to head. Objective: The objective of the study was to investigate the relationship between mitotane dose and plasma concentration comparing two dosing regimens. Design/Setting: This was a prospective, open-label, multicenter trial of a predefined duration of 12 weeks. Patients/Interventions: Forty mitotane-na\uefve patients with metastatic adrenocortical carcinoma were assigned to a predefined low- or high-dose regimen by the local investigator. Thirty-two patients could be evaluated in detail. Main Outcome Measure: The difference in median mitotane plasma levels between both treatment groups was measured. Results: Despite a difference in mean cumulative dose (440 \ub1 142 g vs 272 \ub1 121 g), median maximum plasma levels were not significantly different between the two groups [high dose 14.3 mg/L (range 6.3-29.7, n = 20) vs 11.3 mg/L (range 5.5-20.0, n = 12), P = .235]. Ten of 20 patients onthe high-dose regimen reached plasma concentrations of 14 mg/L or greater after 46 days (range 18-81 d) compared with 4 of 12 patients on the low-dose regimen after 55 days (range 46-74 d, P = .286). All patients who reached 14 mg/L at 12 weeks displayed a level of 4.1 mg/L or greater 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 \ub1 494 mg/L \ub7 d vs 555 \ub1 168 mg/L \ub7 d (P = .080). Conclusions: The high-dose starting regimen resulted in neither significantly different mitotane levels nor 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

Treatment Patterns and Outcomes for Patients with Adrenocortical Carcinoma Associated with Hospital Case Volume in the United States

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare, aggressive disease with no apparent change in treatment or survival in the United States over the past two decades. Our objective was to determine whether treatment patterns or clinical outcomes vary by hospital case volume. METHODS: Patients with ACC were identified from the National Cancer Database (1998–2011). High-volume centers (HVCs) were defined by a case load of ≥4 cases of primary adrenal malignancy annually, which corresponded to the 90th percentile. All other facilities were considered low-volume centers (LVCs). RESULTS: A total of 2,765 ACC patients were treated across 1,046 facilities. Compared to patients treated at LVCs, patients treated at HVCs were younger (50 vs. 54 years), with larger tumors (11.2 vs. 10.5 cm), and underwent higher rates of surgery (78.8 vs. 73.4 %), radical resection (17.3 vs. 13.9 %), regional lymph node evaluation (23.2 vs. 18.8 %), and chemotherapy including mitotane (43.8 vs. 31.0 %, all p < 0.05). There were no significant differences in median length of stay (5 vs. 5 days), 30-day readmission rates (4.0 % for HVCs vs. 3.9 % for LVCs), or 30-day postoperative mortality rates (1.9 % for HVCs vs. 3.7 % for LVCs). Median overall survival was 2.0 years for HVCs and 1.9 years for LVCs, p = 0.53. After adjusting for patient and tumor characteristics, overall survival did not differ significantly between patients treated at HVCs versus LVCs [HR = 0.89 (95 % confidence interval 0.70, 1.12)]. CONCLUSIONS: Treatment at HVCs was associated with more aggressive surgical resection and chemotherapy use. Prognosis remained poor despite more aggressive treatment