Cancer Chemotherapy 4: Clinical Aspects and Novel Approaches PDF

latrobe.edu.au Cancer chemotherapy 4: Clinical aspects and novel approaches Dr Ross O’Shea [email protected] La Trobe University CRICOS Provider Code Number 00115M  Cell-kill fraction Chemotherapeu...

latrobe.edu.au Cancer chemotherapy 4: Clinical aspects and novel approaches Dr Ross O’Shea [email protected] La Trobe University CRICOS Provider Code Number 00115M  Cell-kill fraction Chemotherapeutic drugs given in adequate doses will kill constant proportion of cancer cells Each course of chemotherapy or radiation therapy may reduce cancer cells to levels that are eventually controlled by patient’s immune system Aim of each cycle of cancer therapy: to achieve total cancer cell-kill  Cell-kill fraction Numbers of Cells Clinical Significance Present 100 1 101 10 102 100 103 1000 Subclinical 104 10 000 105 100 000 disease 106 1 000 000 107 10 000 000 108 100 000 000 109 1 000 000 000 ~ 1g:clinical symptoms 1010 10 000 000 000 Regional Spread 1011 100 000 000 000 1012 1 000 000 000 000 Metastases 1013 10 000 000 000 000 Lethal Waller DG et al. Medical Pharmacology & Therapeutics (2014), Fig. 52.3  Drug resistance Neoplastic cells can also develop resistance Pass the acquired characteristics on to daughter cells Mechanisms: – Defective activation of drug (e.g. prodrug not converted) – Enhanced inactivation of the drug (e.g. scavenging of drug by protective mechanisms) – Decreased accumulation into cell  Combination chemotherapy A single drug might only have a complete response rate of