4.3. Cancer- Combination Therapies

4.3.1. Principles of Combination Therapies

1. In order to enhance curative effect, to decrease the toxicity and to reduce the drug resistance, combination therapies are often used in the treatment.
2. Advantages of drug combinations:
   • They provide maximal cell kill within the range of tolerated toxicity.
   • They are effective against a broader range of cell cycle phases.
   • They may slow or prevent the development of resistance.

4.3.2. Aspects of Combination Therapies

1. Select drugs according to their phase specific characteristics:
   • The aim of this rule is to urge more G0 phase cells to enter the proliferating cycle so as to increase the amount of tumor cells killed by drugs.
   • For high GF tumor such as acute leukemia, phase specific drugs are firstly used to kill S or M phase cells, and then phase non-specific drugs are used to kill tumor cells in other phases, and finally the above two steps are repeated once again to kill new cell from G0 phase.
   • For low GF tumor such as solid tumors, phase non-specific drugs are firstly used to kill cells of all phases, and then phase specific drugs are used, and finally the above steps are repeated to kill the new cell from G0 phages.
2.   Combinations of antineoplastic drugs with different action mechanism
   • can destroy tumor cells from various biochemical links at same time.
3.   Combinations of antineoplastic drugs with other therapies
   • Examples: chemotherapy plus operation,
   • chemotherapy plus radiotherapy.
4.   Combination of low-toxic drugs with high toxic ones
   • does not obviously increase the toxicity of antineoplastic drugs while the remarkable synergism of anticancer action is produced.
   • Example: bleomycin (light myelosuppression) + mitomycin (serious myelosuppression), which is often used to treat carcinoma of cervix.
5.   Select drugs according to antineoplastic range (spectrum)
6. Use right dose