Treatment with Combined Streptozotocin and Liposomal Doxorubicin in Metastatic Endocrine Pancreatic Tumors

Abstract

Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported. Background: The combination of streptozotocin and doxorubicin has been shown to be superior to streptozotocin and fluorouracil in the treatment of metastatic EPTs. However, the risk of cardiac toxicity from anthracyclins hampers the usefulness of the drug combination. Liposomal doxorubicin has a lower frequency of cardiac adverse events compared to doxorubicin. We wanted to assess the efficacy and safety of combined streptozotocin and liposomal doxorubicin in patients with metastatic EPTs. Methods: Thirty patients with metastatic EPTs were recruited from three medical centers in Norway and Sweden during a time period of 3 years. All patients had histopathologically confirmed diagnoses and bidimensionally measurable lesions. 30 mg/m² of liposomal doxorubicin was administered on day 1 of each cycle. During the first course, 1 g of streptozotocin was given on 5 consecutive days. Thereafter, 2 g of streptozotocin was given on day 1 only. Treatment was repeated every 3 weeks. Results: Twelve of 30 patients (40%) achieved an objective radiological response with a median duration of 9 months. Stabilization of disease was achieved in 17 of 30 patients (57%) for a median duration of 11 months. Only one patient had progressive disease as best response. The 2-year progression-free survival was 18% and the 2-year overall survival was 72%. The treatment was well tolerated. None of the patients experienced cardiac toxicity. Conclusion: We conclude that combined streptozotocin and liposomal doxorubicin is a safe and efficient treatment for EPTs. The efficacy seems to be comparable to that of combined streptozotocin and doxorubicin, whereas the cardiac toxicity clearly favors using the liposomal drug combination.

ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

“…Cytotoxic therapy combinations include: STZ/5-FU (an established therapy) and doxorubicin with STZ as an alternative option; however, the use of doxorubicin is limited by a cumulative dose of 500 mg/m 2 (due to the risk of cardiotoxicity). Therapeutic regimens can be recommended according to Moertel et al (cycles every 6 weeks) or Fjallskog et al (cycles every 3 weeks) [55,56,57]. Data do not support three-drug regimen associations including cisplatin, nor the replacement of 5-FU by capecitabine [58,59,60].…”

Cytotoxic chemotherapy for pancreatic neuroendocrine tumors

“…Streptozocin (Table 1) [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Streptozocin is a nitrosourea alkylating agent that is known to be taken up into cells by the glucose transport protein GLUT2 and to cause cell damage. Because GLUT2 is strongly expressed in pancreatic beta cells, streptozocin has been widely used to create animal models of diabetes mellitus.…”

Systemic Therapy in Incurable Gastroenteropancreatic Neuroendocrine Tumours: A Clinical Practice Guideline

“…The search uncovered eleven relevant randomized prospective studies [9][10][11][12][13][14][15][16][17][18][19] , sixteen nonrandomized prospective studies [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] , and thirteen retrospective studies [36][37][38][39][40][41][42][43][44][45][46][47][48] . Where multiple reports and abstracts were published for a single trial or study, only the most recent full publication was included, unless other reports contained data that were not available in the most recent publication.…”