Chemotherapy nitrosoureas

Stewart DJ, Grahovac Z, Benoit B, et al. Intracarotid chemotherapy with a combination of l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU), cis-diaminedichloroplatinum (cisplatin), and 4 -0-demethyl-l-0-(4,6-0-2-thenylidene-beta-D-glucopyranosyl)epipodophyllotoxin (VM-26) in the treatmentof primary and metastatic brain tumors. Neurosurgery 1984 15(6) 828-833. 

West CR, Avellanosa AM, Barua NR, Patel A, Hong CL Intraarterial l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas a follow-up study. Neurosurgery 1983 13(4)420426. 

Johnson DW, Parkinson D, Wolpert SM, Kasdon DL, Kwan ES, Laucella M, Anderson ML. Intracarotid chemotherapy with l,3-bis-(2-chloroethyl)-l-nitrosourea (BCNU) in 5% dextrose in water in the treatment of malignant glioma. Neurosurgery 1987 20(4) 577-83. 

Wakui A. [Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas.] Gan To Kagaku Ryoho 1982 9(8) 1327-38. 

Wheeler GP, A review of studies on the mechanism of action of tne nitrosoureas, in [Sartorelli AC ed.] Cancer Chemotherapy, volume 30, Washingtoon, DC American Chemical Society.pp87-119,1976... 

Shapiro WR. Studies on the chemotherapy of experimental brain tumors evaluation of l-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, vincristine, and 5-fluorouracil. J Natl Cancer Inst 1971 46 359-368. 

Secondly, environmental exposure to NNO is likely to be low (3) and therefore it is more difficult to identify populations known to be exposed to elevated levels and which could be used to validate the adduct analyses. One situation in which this problem can be solved is with patients undergoing chemotherapy with methylating agents such as N-methyl-N-nitrosourea (37) or, more commonly, procarbazine (Souliotis, V. and Kyrtopoulos, S., 1990, unpublished data). These studies would be valuable to allow correlations between DNA adduct levels and clinical response as well as validating the assays in human samples as has been successfully done with cis-platin (44). 

Cohen RJ, Wiernik PH, Walker MD. Acute nonlymphocytic leukemia associated with nitrosourea chemotherapy report of two cases. Cancer Treat Rep 1976 60 1257-1261. 

The time frame in which pulmonary drug-induced toxicity occurs is also highly variable, ranging from acute hypersensitivity reactions (e.g., methotrexate, nitrofurantoin toxicides) to delayed presentations (e.g., nitrosoureas, or radiation recall seen with bleomycin, as discussed below). This along with the fact that combination treatments have become commonplace, in particular in the context of chemotherapy protocols, may further hamper the clinician s ability to identify the culprit medication. In addition, several drugs may be implicated in an additive or synergistic fashion and further confuse the clinical picture. 

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