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Medical Pharmacology Chapter 33-34: Anticancer Drugs
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Alkylating Agents (Continued):
Classification8
Alkylating Agent
Nitrosourea
Streptozocin (Zanosar) (a.k.a. Steptozotocin)
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Streptozocin (Zanosar) is classified as a nitrosourea and contains a methylnitrosourea moiety linked to the 2-carbon of glucose.1
Not surprisingly, therefore, streptozotocin exhibits a high binding affinity for Langerhans cells.
The mechanism of
action of streptozotocin is based on alkylation and DNA strand
cross-linking.7
As a result of these interactions, DNA synthesis is inhibited.
Furthermore, cytotoxicity maybe also enhanced by streptozotocin-mediated protein modification. Streptozotocin is classified as a cell-cycle nonspecific drug.7
Compared to
most alkylating agents, streptozotocin exhibits very limited bone marrow
toxicity.
Streptozotocin
exhibits clinical activity for treating pancreatic insulin-secreting islet
cell carcinoma.
Absorption, Distribution, Metabolism, Excretion:7
Streptozocin is administered by the intravenous route of administration.7
Response may be noted at approximately the 17 day mark with a median time of 35 days to maximum response.
Streptozotocin concentrates in liver, kidney and pancreatic beta cells.
Streptozotocin is rapidly metabolized mainly by the liver with an elimination half-life of <1 hour.
Urinary excretion predominates and include both the parent agent and its metabolites.7
Clinical Use(s):3
Pancreatic neuroendocrine tumors (PNETs), also or previously known as islet cell carcinomas, arise from pancreatic ductal progenitors.3
Extrapancreatic neuroendocrine tumors (low-to intermediate-grade) are classified as carcinoids, originating along the aerodigestive tract.
Carcinoids exhibit hormone production and usually show an indolent clinical course.
Clinical symptoms are due to secrete hormones, regional or local tumor growth as well as more general metastatic development.
For localized disease, surgical resection is considered the curative approach.
However in metastatic disease or in unresectable disease, long-acting somatostatin analogs enhances both progression-free survival and quality of life.3
For pancreatic
neuroendocrine tumors (PNETs), targeted treatments include everolimus and
sunitinib.3
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Alkylating chemotherapy including drugs such as temozolomide and streptozotocin may be effective as well.
Streptozotocin specifically is clinically used for treating metastatic islet cell pancreatic carcinoma, a pancreatic neuroendocrine tumor.7
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