Lecture-24 - Principles of cancer chemotherapy A clonogenic...

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Principles of cancer chemotherapy 1. A clonogenic cell has the potential to produce progeny to such an extent that results in the death of the host. The goal of chemotherapy is to kill all clonogenic cells . 2. A constant fraction of cancer cells is killed by an antineoplastic drug per unit time. Eg. if a malignant tumour contains 10 12 cells, killing 99.99% of these cells with an antineoplastic drug (good enough for clinical remission) would still leave 10 8 cells that could regrow. A second treatment would again kill 99.99% of cells, leaving 10,000 cells. 3. Some cancer chemotherapeutic drugs have very steep dose- response curves . Most treatments are given at the highest tolerable dosages and bone marrow transplantation can be used if the antineoplastic drug dose used needs to be even higher. 4. Tumours may grow in body compartments (eg. CNS) to which chemotherapeutic agents have limited access. Local administration of drug may be necessary.
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1. Most antineoplastic drugs have a low therapeutic index and are not at all specific in their actions on cancer cells. Damage also occurs to other dividing tissues such as bone marrow, gonads, oral and g.i. mucosa, and hair follicles. 2. Doses & schedules of antineoplastic drug delivery are limited by tissue tolerance. High-dose intermittent schedules are more effective than low-dose daily administration. Intermittent delivery allows for tissue recovery between treatment cycles. 3. Combination chemotherapy (several different drugs used together) works better than drugs used individually. Best if each drug has a different mechanism of action as well as qualitatively different toxicity (so each drug may be given at near its maximum tolerated dose). 4. Theoretically best to start when there are few cells and when many may be still in cycle and few are resistant to therapy. Adjuvant chemotherapy : administration of drugs to patients who show no evident signs of cancer but are at high risk of developing recurrent cancer (eg. tamoxifen after breast or colorectal cancer therapy), additional treatment, usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to occult disease .
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1. Combined-modality treatments (from surgery, radiation and chemotherapy) are commonly used, and appear to be especially useful in the treatment of childhood cancers.
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Classification of antineoplastic drugs 1. Alkylating and DNA binding agents 2. Antimetabolites 3. Antibiotics 4. Natural plant derivatives 1. Miscellaneous 1. Hormones
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1. Alkylating agents
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This note was uploaded on 04/01/2009 for the course BIO 51310 taught by Professor Sisson during the Spring '08 term at University of Texas at Austin.

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Lecture-24 - Principles of cancer chemotherapy A clonogenic...

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