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

2

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

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

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

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

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

Fig. 100-1. The cell cycle. 8

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

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

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

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

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

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

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

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