Japanese Journal of Clinical Oncology Advance Access originally published online on January 24, 2009
Japanese Journal of Clinical Oncology 2009 39(3):183-185; doi:10.1093/jjco/hyn146
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© The Author (2009). Published by Oxford University Press. All rights reserved
Metastatic Adrenocortical Carcinoma Treated with Sunitinib: A Case Report
1 Department of Internal Medicine
2 Department of Pathology
3 Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
For reprints and all correspondence: Keun-Wook Lee, Department of Internal Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeongi-do 463-707, Republic of Korea. E-mail: hmodoctor{at}hanmail.net
Received July 30, 2008; accepted November 30, 2008
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Abstract |
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 TOP Abstract INTRODUCTIONCASE REPORTDISCUSSIONConflict of interest statementReferences |
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Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Palliative chemotherapy can be considered in patients with metastatic disease. Although mitotane- or cisplatin-based chemotherapy regimens are widely used, the effects of these agents have been limited. We have experienced a case that showed a partial response with sunitinib after failure of mitotane-based cytotoxic chemotherapy. The clinical benefit from sunitinib persisted 7.5 months in this case. To our knowledge, this is the first reported case showing the effects of sunitinib on metastatic ACC.
Key Words: adrenocortical carcinoma • chemotherapy • sunitinib
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INTRODUCTION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONConflict of interest statementReferences |
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Adrenocortical carcinoma (ACC) is a rare malignancy, accounting annually for 0.02% of all cancers reported, with dismal prognosis (1,2). Complete surgical resection of the tumor can offer the best chance for cure, but has high recurrence rate (3). Although mitotane has been widely used for adjuvant chemotherapy, the effectiveness of adjuvant therapy after resection has remained controversial (4). In recurrent or metastatic cases, mitotane- or cisplatin-based chemotherapeutic regimens are widely used. The combination of etoposide, doxorubicin, cisplatin and mitotane showed a response rate (RR) of 49% in advanced ACC (5). Streptozotocin plus mitotane chemotherapy also yielded positive results (RR = 36%) (6). However, as these clinical trials were small-sized and no results of prospective randomized trials have been available, the chemotherapeutic regimen for recurred or metastatic ACC has not been standardized (7). Especially, patients with advanced ACC resistant to mitotane or cytotoxic chemotherapy have few treatment options. Here, we report a case of recurred ACC that showed a partial response (PR) to sunitinib treatment after mitotane-based cytotoxic chemotherapy failure.
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CASE REPORT |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONConflict of interest statementReferences |
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A 21-year-old male presented with pain and a palpable mass in the right upper quadrant (RUQ) of the abdomen. A computed tomography (CT) scan of the abdomen showed a 21 x 16 x 14 cm mass in the right adrenal gland (Fig. 1). There was no evidence of distant metastasis and right adrenalectomy and nephrectomy were performed. The pathologic evaluation confirmed an ACC with capsular and angiolymphatic invasion which had extensive necrosis and hemorrhage (Fig. 2A). The cancer cells had marked nuclear polymorphism and high mitotic rate (Fig. 2B). The immunohistologic staining for vascular endothelial growth factor (VEGF) was focal positive in tumor cells (Fig. 2C). He received adjuvant radiation therapy (RT) of 45 Gy delivered to the tumor bed. Six months after surgery, a CT scan of the chest showed multiple lung metastases and the patient and his family declined chemotherapy. Eleven months after surgery, periumbilical abdominal pain developed and a CT scan showed bulky hepatic and aortocaval lymph node metastases. After palliative RT to the aortocaval lymph nodes for pain control, etoposide, doxorubicin, cisplatin and mitotane chemotherapies were initiated. However, after three cycles of chemotherapy, he developed RUQ abdominal pain and a follow-up CT scan showed progressive disease (PD). Palliative RT was directed to the increased hepatic mass for symptom control, after which he received sunitinib (50 mg/day) in 6-week cycles (4 weeks of treatment and 2 weeks off of treatment). The sunitinib dose was decreased to 37.5 mg/day due to combined toxicities of neutropenia and fatigue. The sizes of the metastatic pulmonary nodules decreased in 6 weeks after the initiation of sunitinib and a PR was achieved in 4 months (Fig. 3A and B). The clinical benefit of sunitinib continued for 7.5 months. After 7.5 months of sunitinib treatment, however, the sizes of the pulmonary metastatic nodules increased and PD was confirmed. Then, he received mitotane and streptozotocin chemotherapies, but a follow-up CT scan showed PD. He is now receiving supportive care only.
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DISCUSSION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONConflict of interest statementReferences |
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Mitotane and/or cytotoxic chemotherapies are treatment schemes most frequently used in advanced ACC, with limited efficacy. Based on the recent availability of molecularly targeted agents for the treatment of several tumors, there has been an attempt to use new targeted agents to treat ACC.
Imatinib is not effective in patients with ACC expressing c-kit and/or platelet derived growth factor (PDGF) receptor (8). However, a recent study showed that patients with ACC had significantly higher serum levels of circulating VEGF than those with benign adrenal tumors or normal subjects (9). Some studies have correlated the serum levels of VEGF with adrenal tumor aggressiveness and clinical outcome (10). Although there are few data on ACC treated with anti-angiogenic drugs, thalidomide, which is a strong anti-angiogenic agent, showed a PR in a patient with ACC that failed to respond to conventional mitotane-based chemotherapy (11). These findings suggest that angiogenesis is an important mechanism related to tumorigenesis of ACC, and thus targeting angiogenesis may have therapeutic effects on ACC.
Sunitinib is an oral multi-targeted tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activities, which has been successfully used in the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumor (12,13). Until now, no data exists on sunitinib in ACC. Our report shows a clinical benefit from sunitinib in a patient with ACC who failed previous cytotoxic chemotherapy. Currently, a phase II study [Sunitinib in Refractory ACC (SIRAC)] is recruiting patients with advanced ACC that has progressed after previous cytotoxic chemotherapy. This phase II study is expected to demonstrate the effects of sunitinib on ACC and the results of this study are eagerly awaited.
In conclusion, sunitinib showed a significant anti-tumor activity in our case with chemo-refractory advanced ACC.
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Conflict of interest statement |
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None declared.
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References |
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