Chapter 100
Basic Principles of Cancer
Chemotherapy
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Cancers
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Most common cancers
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Solid tumors of the breast, lung, prostate, colon,
and rectum
Low growth fraction and respond poorly to drugs
Rarer cancers
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Lymphocytic leukemia, Hodgkin’s disease, certain
testicular cancers
High growth fraction and respond well to drugs
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Basic Principles of Cancer
Chemotherapy
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Cancer – unregulated cellular proliferation
Treatment modalities
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Surgery
Radiation
Drug therapy
• Treatment of choice for disseminated cancers (leukemia,
disseminated lymphomas, wide-spread metastases)
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Basic Principles of Cancer
Chemotherapy
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Drug classes
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Cytotoxic agents
Hormones and hormone antagonists
Biologic response modifiers
Targeted drugs
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Characteristics of Neoplastic Cells
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Persistent proliferation
Invasive growth
Formation of metastases
Immortality
Etiology of cancer
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The Growth Fraction and Its
Relationship to Chemotherapy
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The cell cycle
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Four major phases
The growth fraction
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Impact of tissue growth fraction on
responsiveness to chemotherapy
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Fig. 100-1. The cell cycle.
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Tissue Growth and Chemotherapy
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Chemotherapy drugs are more toxic to tissue
with high growth fraction
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Bone marrow
Skin
Hair follicles
Sperm
Gastrointestinal tract
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Obstacles to Successful
Chemotherapy
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Toxicity to normal cells
Cure requires 100% cell kill
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Kinetics of drug-induced cell kill
Host defenses contribute little to cell kill
When should treatment stop?
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Fig. 100-2. Gompertzian tumor growth curve showing the relationship between tumor size
and clinical status.
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Obstacles to Successful
Chemotherapy
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Absence of truly early detection
Solid tumors respond poorly
Drug resistance
Heterogeneity of tumor cells
Limited drug access to tumor cells
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Strategies for Achieving Maximum
Benefits from Chemotherapy
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Intermittent chemotherapy
Combination chemotherapy
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Benefits of drug combinations
Suppression of drug resistance
Increased cancer cell kill
Reduced injury to normal cells
Optimizing dosing schedules
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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.
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Strategies for Achieving Maximum
Benefits from Chemotherapy
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Regional drug delivery
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Intra-arterial
Intrathecal
Other specialized routes
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Major Toxicities of Cancer
Chemotherapy
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Bone marrow suppression
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Neutropenia
Thrombocytopenia
Anemia
Digestive tract injury stomatitis
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Nausea, vomiting, diarrhea
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Major Toxicities of Cancer
Chemotherapy
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Alopecia
Hyperuricemia
Reproductive toxicity
Local injury from extravasation of vesicants
Unique toxicities
Carcinogenesis
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Making the Decision to Treat
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Benefits of treatment must outweigh the risks
Patient must be given some idea of the
benefits of proposed therapy
One of these three should be possible:
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Cure, prolongation of life, palliation
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