1. Basic Principles of Cancer Chemotherapy
Chapter 101
Basic Principles of Cancer Chemotherapy 1

2. 2

3. Cancers Most common cancers Rarer cancers
Solid tumors of the breast, lung, prostate, colon, and rectum
Low growth fraction and respond poorly to drugs
Rarer cancers
Lymphocytic leukemia, Hodgkin’s disease, certain testicular cancers
High growth fraction and respond well to drugs 3

4. Basic Principles of Cancer Chemotherapy
Cancer – unregulated cellular proliferation
Treatment modalities
Surgery
Radiation
Drug therapy
Treatment of choice for disseminated cancers (leukemia, disseminated lymphomas, wide-spread metastases) 4

5. Basic Principles of Cancer Chemotherapy
Drug classes
Cytotoxic agents
Hormones and hormone antagonists
Biologic response modifiers
Targeted drugs 5

6. Characteristics of Neoplastic Cells
Persistent proliferation
Invasive growth
Formation of metastases
Immortality 6

7. The Growth Fraction and Its Relationship to Chemotherapy
The cell cycle
Four major phases
The growth fraction
Impact of tissue growth fraction on responsiveness to chemotherapy 7

8. Fig The cell cycle. 8

9. Tissue Growth and Chemotherapy
Chemotherapy drugs are more toxic to tissue with high growth fraction
Bone marrow
Skin
Hair follicles
Sperm
Gastrointestinal tract 9

10. Obstacles to Successful Chemotherapy
Toxicity to normal cells- this is the BIGGEST IMPEDIMENT TO SUCCESSFUL THERAPY
Cure requires 100% cell kill
Kinetics of drug-induced cell kill
Host defenses contribute little to cell kill
When should treatment stop? 10

11. Fig. 100-2. Gompertzian tumor growth curve showing the relationship between tumor size
and clinical status. 11

12. Obstacles to Successful Chemotherapy
Absence of truly early detection
Solid tumors respond poorly
Drug resistance
Heterogeneity of tumor cells
Limited drug access to tumor cells 12

13. Strategies for Achieving Maximum Benefits from Chemotherapy
Intermittent chemotherapy
Combination chemotherapy
Benefits of drug combinations
Suppression of drug resistance
Increased cancer cell kill
Reduced injury to normal cells
Optimizing dosing schedules 13

14. Fig. 100-3. Recovery of critical normal cells during intermittent chemotherapy.
Cancer cells and normal cells (eg, cells of the bone marrow) are killed each time drugs are given. In the interval between doses, both types of cells proliferate. Because, in this example, normal cells repopulate faster than the cancer cells, normal cells are able to recover entirely between doses, whereas regrowth of the cancer cells is only partial. As a result, with each succeeding round of treatment, the total number of cancer cells becomes smaller, whereas the number of normal cells remains within a tolerable range. Note that differential loss of malignant cells is possible only if these cells repopulate more slowly than the normal cells. If cancer cells grow back as fast as normal cells do, intermittent chemotherapy will fail. 14

15. Major Toxicities of Cancer Chemotherapy
Bone marrow suppression
Neutropenia (If ANC drops below 500 cells/mm³ therapy should be stopped)
G-CSF (Filgrastim) can be given to stimulate neutrophil productio
neutropenia typically presents as fever, and can be life-threatening, promptly evaluate temp ≥ 100.4)
Thrombocytopenia (platelet infusion can be given if severe)
Anemia- erythropoietin (Epogen) can be given to boost RBCs if the goal is palliative treatment
Digestive tract injury
stomatitis
Nausea, vomiting, diarrhea 15

16. Major Toxicities of Cancer Chemotherapy
Alopecia- hair loss
Hyperuricemia- can cause kidney damage, allopurinol can be administered)
Reproductive toxicity
Local injury from extravasation of vesicants
Unique toxicities
Carcinogenesis 16