A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma

Abraham, Jame; Bakke, Susan; Rutt, Ann; Meadows, Beverly; Merino, María J.; Alexander, Richard B.; Schrump, David S.; Bartlett, David L.; Choyke, Peter L.; Robey, Robert W.; Hung, Elizabeth; Steinberg, Seth M.; Bates, Susan E.; Fojo, Tito

doi:10.1002/cncr.10487.abs

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…The systemic agents for ACC most commonly described in the literature have been mitotane, etoposide, and cisplatin, used together or in various combinations with other agents. Overall response rates have typically varied from 11 to 30% [9][10][11][12]. In a phase II trial, Berruti et al [13] prospectively assigned 75 patients to treatment with cisplatin, etoposide, doxorubicin, and mitotane.…”

Section: Discussionmentioning

confidence: 98%

Systemic chemotherapy for adrenocortical carcinoma: comparative responses to conventional first-line therapies

Fareau

López²,

Stava³

et al. 2008

Anti-Cancer Drugs

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The objective of this study was to evaluate and compare the efficacies of conventional first-line chemotherapies for adrenocortical carcinoma. We reviewed the records of adult patients (> or =17 years) who had received first-line systemic chemotherapy with serial pretreatment and posttreatment radiologic staging studies in our institution between 1980 and 2000. Overall survival (OS) and time to progression (TTP) for different treatment groups were determined using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate models were fitted to different subsets of patients for OS and TTP and used to calculate hazard ratios (HRs) with 95% confidence intervals. We identified 224 patients with a diagnosis of adrenocortical carcinoma, 57 of whom met the inclusion criteria for further study. Chemotherapy groups included: mitotane (n=12), platinum and etoposide (n=16), mitotane with platinum and etoposide (n=11), mitotane and other cytotoxics (n=5), platinum and etoposide with other cytotoxics (n=3), and other miscellaneous cytotoxics (n=10). No statistically significant differences in OS (P=0.31) were noted among the treatment groups, but there was a statistically significant difference in TTP (P=0.02) favoring mitotane alone (TTP=6.24 months; 95% confidence interval, 3.58-32.13). Multivariate analysis was most notable for a significantly greater OS (HR=0.49, P=0.04) and TTP (HR=0.3, P=0.01) associated with peritoneal metastases. Our analysis revealed no clear advantage for any single agent or combination over any of the other conventional frontline chemotherapeutic choices for adrenocortical carcinoma. Novel agents are thus sorely needed in the treatment of this aggressive cancer.

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Section: Discussionmentioning

confidence: 98%

Systemic chemotherapy for adrenocortical carcinoma: comparative responses to conventional first-line therapies

Fareau

López²,

Stava³

et al. 2008

Anti-Cancer Drugs

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“…Cisplatin has also been investigated in combination with etoposide 33,73,74. The combination of doxorubicin, etoposide, and vincristine without cisplatin appears to induce an inferior antitumor effect 75. Because of cisplatin's renal dose‐limiting toxicity, Ayass and coworkers substituted carboplatin for cisplatin given in combination with etoposide to a 17‐month‐old boy with ACT that had metastasized to the brain and chest.…”

Section: Treatment Of Adrenocortical Tumorsmentioning

confidence: 99%

“…Responses have been observed in 53% of patients treated with mitotane and cisplatin, etoposide, and doxorubicin 80. However, other studies have failed to confirm these positive results 75. Abraham et al found that rhodamine efflux from CD56 + cells (a surrogate marker of Pgp inhibition) was not impaired in patients receiving chemotherapy and mitotane, even at therapeutic drug levels; therefore, mitotane may inhibit Pgp poorly in vivo 75.…”

Section: Treatment Of Adrenocortical Tumorsmentioning

confidence: 99%

Biology, clinical characteristics, and management of adrenocortical tumors in children

Rodríguez‐Galindo

Figueiredo

Zambetti

et al. 2005

Pediatric Blood & Cancer

129

104

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Childhood adrenocortical tumors (ACT) are very aggressive endocrine neoplasms whose incidence is quite low. Little is known about their pathogenesis, clinical presentation, and optimal treatment. In recent years, however, new information has been derived from the International Pediatric Adrenocortical Tumor Registry (IPACTR), and new clues to its pathogenesis have emerged. To provide an overview of the available data that may apply to pediatric ACT, we reviewed the epidemiology, pathogenesis, and treatment of ACT in adults and in children. Germline TP53 mutation is almost always the predisposing factor in childhood ACT. A unique germline mutation (TP53-R337H) has been described in Southern Brazil, where the incidence of ACT is 10-15 times the general incidence. Childhood ACT typically present during the first 5 years of life and has female predominance. Hormone hyperproduction is almost universal, and most patients present with virilization. Two-thirds of patients have resectable tumors. Surgery is the definitive treatment for ACT, and a curative complete resection should always be attempted. Cisplatin-based chemotherapy with mitotane is indicated for unresectable or metastatic disease, although its impact on overall outcome is slight. In childhood ACT, age, tumor size, and tumor resectability are the most important prognostic indicators. Outcome is stage-dependent; patients with small, resectable tumors have survival rates in excess of 80%, whereas the outcome for patients with unresectable disease is dismal. Patients with large, resectable tumors have an intermediate outcome. Childhood ACT are rare, but their unique epidemiology appear to implicate novel oncogenic pathways that are unique to the pediatric population. Multi-institutional and prospective studies are necessary to further our understanding of the pathogenesis and to improve outcomes.

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“…In contrast, chemotherapy following a local resection has shown a better patient survival. [2][3][4][5][6][7][8][9] Therefore, a complete surgical excision is essential for prolonged survival. On the other hand, pulmonary metastasis from ACC is very rare with regard to metastatic lung tumors.…”

Section: Introductionmentioning

confidence: 99%

Alpha-fetoprotein (AFP)-producing adrenocortical carcinoma — Long survival with various therapeutic strategies including a lung resection: Report of a case

et al. 2008

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We experienced a very rare case of late pulmonary metastasis from ACC. The patient was a 40-year-old woman who had undergone a left adrenectomy 12 years earlier. Instead of a large metastatic lung tumor with hemothorax and the existence of metastases in other organs, combined therapy of repeated resections for metastases and adjuvant therapy allowed for almost a 36-month survival following the first recurrence and a good quality of life. In addition, a blood and pathological study revealed that the tumor in this case was an alpha-fetoprotein-producing ACC, which is, as far as we could ascertain, the first case of its kind.

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A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma

Cited by 4 publications

References 9 publications

Systemic chemotherapy for adrenocortical carcinoma: comparative responses to conventional first-line therapies

Systemic chemotherapy for adrenocortical carcinoma: comparative responses to conventional first-line therapies

Biology, clinical characteristics, and management of adrenocortical tumors in children

Alpha-fetoprotein (AFP)-producing adrenocortical carcinoma — Long survival with various therapeutic strategies including a lung resection: Report of a case

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