The treatment of adrenocortical carcinoma with o,p′-DDD: Prognostic simplications of serum level monitoring

Slooten, H. van; Moolenaar, A. J.; Seter, A.P. van; D, Smeenk

doi:10.1016/0277-5379(84)90033-6

Cited by 186 publications

(118 citation statements)

References 29 publications

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“…Apart from the effectiveness of mitotane treatment, there are no major differences between our study and that of Luton et al. The discrepancy in findings between the two studies may lie in the different dosages of the drug used (or serum concentrations reached), as was suggested by van Slooten et al in 1984(Haak et al, 1990. In the present study, an objective tumour response, according to the strict WHO criteria, was found in 15 of the 27 evaluable patients with levels above 14 mg 1'.…”

Section: Discussioncontrasting

confidence: 66%

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Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients

Haak

Hermans²,

Cj³

et al. 1994

Br J Cancer

306

229

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Summary Mitotane is considered to be the drug of choice for patients with inoperable, recurrent and metastatic adrenocortical carcinoma, although a favourable effect of this drug on survival has never been documented. We evaluated the efficacy of mitotane treatment of 96 patients with adrenocortical carcinoma followed up in our department between 1959 and 1992. Complete tumour resection was the goal of the initial treatment. Mitotane treatment was classified according to serum trough concentrations on maintenance therapy: low (<14mgl-') or high (>14mg1-'). Total tumour resection was feasible in 47 patients (49%), and subtotal resection was performed in 37 patients (39%). Patients who underwent total tumour resection survived significantly longer than those who did not (P<0.001). Adjuvant mitotane therapy (n = 11) did not influence survival after total resection. Sixty-two patients were given mitotane treatment at some time during their illness, only 30 of whom reached high maintenance serum levels. Mitotane treatment with high serum levels had an independently favourable influence on patient survival, using univariate (P<0.01) and multivariate analysis (P = 0.01). Mitotane treatment resulting in low serum levels was tantamount to not giving mitotane at all. We conclude that mitotane treatment in adrenocortical carcinoma is effective only when high serum levels can be achieved.

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Section: Discussioncontrasting

confidence: 66%

“…However, a recently completed retrospective (multivariate) analysis of 105 patients with carcinoma of the adrenal cortex failed to document improved survival due to mitotane therapy (Luton et al, 1990). In a retrospective study conducted in our hospital (van Slooten et al, 1984) (Mathews & Farewell, 1985).…”

mentioning

confidence: 97%

Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients

Haak

Hermans²,

Cj³

et al. 1994

Br J Cancer

306

229

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“…Our study highlights that monitoring of plasma mitotane concentrations is of particular interest in controlling hypercortisolism. The narrow therapeutic range of mitotane is well known, and a target plasma concentration between 14 and 20 mg/l is recommended in adrenocortical cancer (31,32,33). However, the target concentration for the anti-cortisolic effect is not well established.…”

Section: Discussionmentioning

confidence: 99%

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Baudry

Coste

Khalil

et al. 2012

European Journal of Endocrinology

164

118

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Context: Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first-or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD. Objective: Evaluation of the efficacy and tolerance of mitotane in CD patients. Design and setting: Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. Main outcome measure: Remission was defined as normalization of 24-h urinary free cortisol (24-h-UFC). Results: Remission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2-8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5G8.9 mg/l, with a mean daily dose of 2.6G1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P!0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0-67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32-1.00), PZ0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery. Conclusion: Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients.

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“…Maintenance mitotane serum levels, determined according to the method previously described (Moolenaar et al, 1977) were classified as low (<14mg 1') or high (> 14 mg I`) (van Slooten et al, 1984a). Other chemotherapeutic agents were given in addition to mitotane in the presence of tumour progression, when the patient refused mitotane therapy, or as judged by the attending physician.…”

Section: Methodsmentioning

confidence: 99%

Nuclear DNA content and morphological characteristics in the prognosis of adrenocortical carcinoma

Haak

Cornelisse²,

Hermans³

et al. 1993

Br J Cancer

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Summary Prognostic factors are needed for the management of patients with adrenocortical tumours. For this reason, the nuclear DNA content of patients with adrenocortical tumours was analysed by flow cytometry. The relationships between nuclear DNA content, histological indices, and clinical parameters were studied. DNA ploidy could be evaluated in 54 carcinoma and 31 adenoma patients. Twenty-one (68%) of the adenomas, and 6 (11%) of the carcinomas, were DNA diploid. Hypo/Hyperdiploidy was found in 5 (16%) of the adenomas, and 15 (28%) of the carcinomas. The remaining patients had a DNA index above 1.40. A shorter survival was found in patients with diploid carcinomas (P <0.05). A longer disease-free survival was seen in patients with hypo/hyperdiploid carcinomas (P <0.05). Nuclear DNA content was not related to the histological index, nor to clinical parameters. We conclude that nuclear DNA content is related to (diseasefree) survival of patients with adrenocortical carcinomas. An adenoma-carcinoma sequence may be present in the adrenal cortex. In adrenocortical tumours ploidy evolution appears to be different than that observed in other solid tumours.

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The treatment of adrenocortical carcinoma with o,p′-DDD: Prognostic simplications of serum level monitoring

Cited by 186 publications

References 29 publications

Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients

Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Nuclear DNA content and morphological characteristics in the prognosis of adrenocortical carcinoma

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