Key Members
– Carmustine
– Lomustine
– Streptozocin
• They are bifunctional alkylating agents
• Active against a wide spectrum of human malignancies
• Carmustine (BCNU) and lomustine (CCNU) are highly lipophilic an
...
Key Members
– Carmustine
– Lomustine
– Streptozocin
• They are bifunctional alkylating agents
• Active against a wide spectrum of human malignancies
• Carmustine (BCNU) and lomustine (CCNU) are highly lipophilic and hence cross BBB.
• Useful in the treatment of meningeal leukemias and brain tumors.
• Generally lack cross resistance with other alkylating agents
• All nitrosoureas except streptozocin cause profound cumulative myelosuppression and this restricts their therapeutic use
• Long term treatment with these agents especially semustine (methyl CCNU) results in renal failure with lesions resembling radiation induced nephritis
• Nitrosoureas are both carcinogenic and mutagenic just like the other alkylating agent
Carmustine
• 1st nitrosourea to receive extensive clinical evaluation
• It is a cell – phase non specific antineoplastic agent
• It is effective against a wide range of tumors
Clinical Uses:
• e.g. primary and metastatic brain tumors,
• an adjunct in meningeal leukemia
• combination chemotherapy for multiple myeloma Hodgkin’s disease and other lymphomas, breast, bronchogenic renal-cell carcinomas, gastrointestinal tumors
Administration and Doses:
• Given i.v. as a single dose of 100-200mg/m2 administered over a period of 1-2 hours and should not be repeated until after 6 weeks
• When used in combination with other chemotherapeutic agent the dose is reduced by 25 to 50%
• Subsequent doses are adjusted according to the haematological picture
• has rapid tissue uptake and metabolism with plasma t ½ of 90 minutes
• 80% is excreted as metabolites in 24 hours.
Clinical Toxicity
• Delayed cumulative bone marrow depression is the most frequent and serious side effect probably caused by active metabolites
• Causes local burning pain during injection. However the drug is not a vesicant
• Nausea and vomiting occur 2 hours after injection
• Flushing of the skin and conjunctiva
Clinical Toxicity cont--
• CNS toxicity,
• oesophagitis, diarrhoea, dyspnoea,
• interstitial pulmonary fibrosis,
• renal and hepatic toxicity
• Potential carcinogenicity, mutagenicity and teratogenicity
• Severe retinal toxicity and blindness in pts receiving intra-arterial carotid infusions of carmustine
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