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Year : 2018  |  Volume : 14  |  Issue : 5  |  Page : 1149-1151

Durable complete response with a short course of streptozotocin plus doxorubicin combination in malignant metastatic insulinoma

Department of Medical Oncology, Diskapi Yildirim Beyazid Education and Research Hospital, Ankara, Turkey

Date of Web Publication7-Sep-2018

Correspondence Address:
Fatih Karatas
Irfan Bastug Street, Ulus/Diskapi, Ankara
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.188293

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 > Abstract 

Due to the cytotoxic effects of old chemotherapy regimens used in the islet cell tumors, capecitabine plus temozolomide combination has now become the first choice in the treatment of malignant insulinoma (MIoma). We present this case to emphasize and remind that a durable complete response in advanced stage MIoma may be achieved with a short course of streptozotocin plus doxorubicin combination.

Keywords: Doxorubicin, durable response, insulinoma, pancreatic neuroendocrine tumors, short course, streptozotocin

How to cite this article:
Karatas F, Sahin S, Aytekin A, Hacioglu MB, Imamoglu GI, Altinbas M. Durable complete response with a short course of streptozotocin plus doxorubicin combination in malignant metastatic insulinoma. J Can Res Ther 2018;14:1149-51

How to cite this URL:
Karatas F, Sahin S, Aytekin A, Hacioglu MB, Imamoglu GI, Altinbas M. Durable complete response with a short course of streptozotocin plus doxorubicin combination in malignant metastatic insulinoma. J Can Res Ther [serial online] 2018 [cited 2021 Oct 25];14:1149-51. Available from: https://www.cancerjournal.net/text.asp?2018/14/5/1149/188293

 > Introduction Top

While assessing the response to chemotherapy in malignancies, following parameters such as tumor size, symptomatic response, progression-free survival along with overall survival are the most considered factors.[1] In general, the vast majority of the previous studies regarding the response assessments to treatments used in the malignant insulinoma (MIoma) have evaluated the cases that successfully completed the treatment cycles. By contrast, there are only a few studies assessing the activity of chemotherapy treatments (ChTs) which were discontinued due to drug-related adverse events. It is highly important to note that the likelihood of long-lasting antitumor activity of ChT following treatment discontinuation is as important as the main drug efficacy during the administration of ChT.[2]

Systemic chemotherapy for advanced pancreatic endocrine tumors has been investigated with either single or combination regimens over the last three decades. Streptozotocin was approved by the Food and Drug Administration in 1976 for the treatment of pancreatic neuroendocrine tumors. Today, streptozotocin plus doxorubicin (S + D) ChT regimen was replaced by less toxic agents such as temozolomide plus capecitabine (T + C) combination in the metastatic setting of MIoma. Nonetheless, it is still known that S + D combination seems to be one of the most effective treatment options in the treatment of MIoma.[3]

 > Case Report Top

A 62-year-old man presented with the complaints of tremor, sweating, and loss of consciousness. Physical examination and vital signs had no significant findings. Initial blood tests including complete blood count and biochemical analysis at arrival were as follows: white blood cell 12,000/mm 3; platelet 155 × 103/mm; hemoglobin 14.5 g/dL; fasting blood glucose (FBG) 45 mg/dL (range, 70–100); insulin 44 IU/mL (range, 4.8–6.0); and C-peptide 6.3 pmol/mL (range, 0.15–1.30). Abdominal computed tomography (CT) imaging detected a solid mass 23 mm × 27 mm in size favoring a malignant appearance in the body of the pancreas and multiple metastatic lesions in the liver [Figure 1]. Pathological examinations of the liver lesions revealed a Grade II neuroendocrine tumors stained positive with panCK, chromogranin A, synaptophysin, CD56, and Ki-67 (10–15%). Ga-68 DOTATOC whole body positron emission scan showed pathological involvements for the lesions previously determined in CT screening. On the basis of these clinical and radiological findings, the patient was diagnosed as MIoma and was commenced on S + D (streptozotocin [500 mg/m 2 daily, for the first 5 days, every 6 weeks] + doxorubicin [50 mg/m 2 daily, on the 1st day, every 3 weeks]) combination. After the 1st week of ChT initiation, rapid improvement in clinical symptoms along with a significant reduction in the need of glucose infusion was observed. On the follow-up, patient's FBG was within normal levels, and the need of glucose infusion was abolished. After the 2nd cycle of ChT, insulin and C-peptide levels (24 IU/mL and 2 pmol/mL, respectively) were decreased, with a remarkable improvement in patient's performance. Radiologically, the size of primary pancreatic mass and liver metastasis was reduced with a rate of 30%. However, after the 2nd cycle of ChT, the patient had congestive heart failure associated with doxorubicin treatment; hence, the treatment was discontinued. Three months later, the patient had no symptom and complaint related to Mİoma, and laboratory tests including FBG, insulin, and C-peptide levels were within normal range. Furthermore, the primary mass in the pancreas and metastatic lesions in the liver were completely disappeared in control abdominal CT scans [Figure 2]. After the 24th month, the patient still did not repeat any sign or symptom associated with Mİoma and did not have any abnormal laboratory finding for FBG, C-peptide, and insulin levels. Moreover, a CT scan still showed a complete response without any treatment after the 30th month of the diagnosis.
Figure 1: Multiple metastases at liver before treatment

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Figure 2: Complete response 6 months after the treatment

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 > Discussion Top

Insulinoma is the most common pancreatic neuroendocrine cancer accounting for 85% of all pancreatic islet cell tumors. In general, symptoms of the disease begin a few years before the initial diagnosis, particularly neuroglycopenic symptoms. Surgery is the main treatment of solitary insulinoma.[4],[5] Nowadays, percutaneous transhepatic venous sampling in addition to selective adenomectomy during intraoperative sonography has replaced the subtotal/total pancreatectomy.[6] S + D combination with or without 5-fluorouracil (5-FU) therapy was popular in the treatment of metastatic insulinoma in the 1980s; however, today, these regimen has been replaced by less toxic chemotherapeutic agents such as C + T with or without somatostatin analogs. The highest response rates were observed in the S + D combination group in a randomized, prospective trial by Moertel et al. in 1992 that was the first study comparing S + D with S + 5-FU + chlorozotocin combination in 102 patients with metastatic pancreatic neuroendocrine tumors.[7] Recently, in another study by Strosberg et al. on 30 patients, an objective radiographic response was achieved in 21 patients with T + C combination,[8] indicating a progression-free survival of 18 months along with a 2 years survival rate of 92%.[8] It is clear that there need to be much more randomized trials comparing the combination regimens with each other or with hormone therapy or with new tyrosine kinase inhibitors such as sunitinib, to identify the optimal treatment for metastatic MIoma. In the current treatment approach, the evident cardiac toxicity of doxorubicin treatment is the most important limitation for the use of S + D combination.[9] However, the fact that Grade III–IV myelosuppression is less frequently seen with S + D combination as compared to C + T regimen should render the S + D combination a more preferable option, particularly in patients without low cardiac ejection fraction (CEF). In the present case, the CEF of the patient decreased to 40% from 60% although anthracycline did not reach to a maximum cumulative toxic dose and the patient developed thrombotic cerebrovascular attack due to new emerging atrial fibrillation.

 > Conclusion Top

The most important point in this case that makes it special was that an ongoing durable complete response for over 30 months has been attained with only a short course of ChT. The patient with advanced MIoma who has no risk for cardiac functions or congestive heart failure should be treated with S + D combination as the first-line treatment option in the metastatic setting.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.  Back to cited text no. 1
O'Toole D, Hentic O, Corcos O, Ruszniewski P. Chemotherapy for gastro-enteropancreatic endocrine tumours. Neuroendocrinology 2004;80 Suppl 1:79-84.  Back to cited text no. 2
de Herder WW, van Schaik E, Kwekkeboom D, Feelders RA. New therapeutic options for metastatic malignant insulinomas. Clin Endocrinol (Oxf) 2011;75:277-84.  Back to cited text no. 3
Hirshberg B, Cochran C, Skarulis MC, Libutti SK, Alexander HR, Wood BJ, et al. Malignant insulinoma: Spectrum of unusual clinical features. Cancer 2005;104:264-72.  Back to cited text no. 4
Starke A, Saddig C, Mansfeld L, Koester R, Tschahargane C, Czygan P, et al. Malignant metastatic insulinoma-postoperative treatment and follow-up. World J Surg 2005;29:789-93.  Back to cited text no. 5
Solbiati L, Ierace T, Goldberg SN, Sironi S, Livraghi T, Fiocca R, et al. Percutaneous US-guided radio-frequency tissue ablation of liver metastases: Treatment and follow-up in 16 patients. Radiology 1997;202:195-203.  Back to cited text no. 6
Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 1992;326:519-23.  Back to cited text no. 7
Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 2011;117:268-75.  Back to cited text no. 8
Silber JH, Barber G. Doxorubicin-induced cardiotoxicity. N Engl J Med 1995;333:1359-60.  Back to cited text no. 9


  [Figure 1], [Figure 2]


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