Mitotane associated with etoposide, doxorubicin, and cisplatin in the treatment of advanced adrenocortical carcinoma

Berruti, Alfredo; Terzolo, Massimo; Pia, Anna; Angeli, Alberto; Dogliotti, Luigi

doi:10.1002/(sici)1097-0142(19981115)83:10<2194::aid-cncr19>3.0.co;2-3

Cited by 105 publications

(44 citation statements)

References 23 publications

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“…Mitotane or op'DDD is the only adrenal-specific agent available for the treatment of adrenocortical carcinoma [25,26]. Because Mitotane could reverse in vitro multidrug resistance, mitotane has usually been used in combination with various chemotherapeutic agents in advanced cases or in an adjuvant setting following curative surgery of adrenocortical carcinoma [25,26].…”

Section: Determination Of Prognostic Factors and Surrogate Markers Ofmentioning

confidence: 99%

“…Because Mitotane could reverse in vitro multidrug resistance, mitotane has usually been used in combination with various chemotherapeutic agents in advanced cases or in an adjuvant setting following curative surgery of adrenocortical carcinoma [25,26]. Objective response to mitotane is achieved in approx 25% of patients with adrenocortical carcinoma but side effects such as those in GI tract, CNS and respiratory system can pose serious problems to the patients [25].…”

Section: Determination Of Prognostic Factors and Surrogate Markers Ofmentioning

confidence: 99%

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Recent advances in histopathology and immunohistochemistry of adrenocortical carcinoma

2006

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Discerning malignancy in resected adrenocortical neoplasms can pose diagnostic difficulty. Macroscopic examination is the first important step toward diagnosis and should include accurate measurement of weight and dimension of the specimens and description of the cut surface of the tumors. It is also important to sample the specimens for histological diagnosis near foci of hemorrhage and/or necrosis. Histological scoring systems evaluating multiple parameters, especially the criteria of Weiss, have been shown to be reliable in differential diagnosis between adrenocortical adenoma and carcinoma. A tumor is defined as adrenocortical carcinoma when three or more of the following criteria are met; (1) high nuclear grade, (2) mitotic rate six or more per 50 high power fields, (3) atypical mitosis, (4) clear cells less than 25%, (5) a diffuse architecture pattern in more than one-third of the tumor, (6) confluent necrosis, (7) venous invasion, (8) sinusoidal invasion, and (9) capsular invasion. The criteria are relatively straightforward and considered the most effective standard for diagnosis of adrenocortical malignancy. However, great care should be taken in applying the criteria to histological evaluation of two relatively rare and peculiar adrenocortical tumors, adrenocortical oncocytoma and pediatric adrenocortical neoplasms. At this juncture, ancillary biological or molecular markers are of little practical value in terms of differential diagnosis between adrenocortical adenoma and carcinoma but tumors with MIB1 or Ki-67 labeling index more than 2.5 may be considered malignant. Prognostic markers of adrenocortical carcinoma have not been established other than complete respectability of the tumor. There are also no surrogate markers for predicting response to therapy with Mitotane, an adrenolytic agent. It sometimes is important for surgical pathologists to differentiate adrenocortical carcinoma from metastatic malignancies of other sites. An immunohistochemical evaluation of adrenal 4 binding protein (Ad4BP) or SF-1, a transcription factor of all steroidogenesis, can aid in this differential diagnosis because nuclear immunoreactivity for this transcription factor is relatively specific to steroid producing cells.

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Section: Determination Of Prognostic Factors and Surrogate Markers Ofmentioning

confidence: 99%

Section: Determination Of Prognostic Factors and Surrogate Markers Ofmentioning

confidence: 99%

Recent advances in histopathology and immunohistochemistry of adrenocortical carcinoma

2006

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“…Although only a limited number of small therapeutic trials have been initiated for ACC, the International Consensus Conference on Adrenal Cancer, held at the University of Michigan in 2003 formally endorsed two "best practice" regimens for advanced disease [11]. The EDP schedule, etoposide, doxorubicin, cisplatin plus mitotane boasts a response rate of approximately 50% with a median survival time of 2 years [12]. Alternatively, a regimen of streptozotocin plus mitotane has induced response rates of approximately 35% with a median survival of 16 months [13].…”

Section: Epidemiology and Clinical Managementmentioning

confidence: 99%

The molecular genetics of adrenocortical carcinoma

Barlaskar

Hammer

2007

Rev Endocr Metab Disord

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“…Vielfach liegen nur kasuistische Mitteilungen vor. Eine aktuelle größere Untersuchung hat die Wirksamkeit einer Kombination von Doxorubincin, Cisplatin und Etoposid in Verbindung mit einer Gabe von Mitotane untersucht [33]. Das Ansprechen war höher als in den zuvor publizierten Serien mit anderen Zytostatikakombinationen bei allerdings auch deutlicher Toxizität.…”

Section: Zytostatische Polychemotherapieunclassified