Pharmacology > LECTURE NOTES > Cancer Chemotherapy Detailed Notes. (All)
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 [Show More]
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Detailed notes on tumor markers and some of the most commonly used chemotherapeutic agents.
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