Principles of Cancer Chemotherapy

Derived from epithelial cells, those cells that line the type of our skin and organs.

Derived from muscle, bone, cartilage, fat or connective tissues

Derived from white blood cells or their precursors

A cancer of bone marrow derived cells that affects the lymphatic system

A cancer involving the white blood cells responsible for the production of antibiodies (B lymphocytes or B-cells)

bladder cancer

hepatoma

lung, mesothelioma

leukemia

liver angiosarcoma

Non-Hodgkin's lymphoma and nasopharyngeal cancer

Kaposi's sarcoma and lymphoma

Cutaneous T-lymphoma

Cervical cancer

Exposure --> damage --> growth alterations and mutations

Reversible changes favors growth of mutated cells

Cells become cancerous

Additional genetic changes increase cancer proliferation

• Defective genes involved in triggering cancer cell growth
• HER-2

• Normal genes responsible for control of cell division.
• p53

• Encodes for the human epidermal growth factor receptor type 2
• It is involved in cellular responses to growth factors.

Encodes for transcirption factor that regulates cell division, by triggering cell death (apoptosis) upon cellular injury.

small localized cancer that are curable

Locally advanced and/or involvement of local lymph nodes

Inoperable or metastatic cancer.

grade cannot be assessed

well differentiated

moderately differentiated

poorly differentiated

undifferentiated (most aggressive and fast growing)

aims to shrink tumor and increase efficacy of primary therapy (reduce tumor cell burden)

• surgery
• radiation
• chemotherapy
• biologic therapy

resection of solid localized tumors

for curing localized tumors

systemic TTT against primary tumor and metastasis

Systemic TTT acts by stimulating host immune system

to eliminate all residual disease

aims to at least reduce tumor burden below 10^3 cells

• when complete eradication is unlikely
• aims to control symptoms, prolong survival time and increase QOL

• Postmitotic phase
• manufacture of enzymes for DNA synthesis

• Resting cells (not preparing division)
• serve as reserve for repopulation of tissue
• Generally not susceptible to chemo, esp. in slow growing tumors.

DNA synthesis and replication

• premitotic phase
• making specialized proteins and RNA

• mitosis
• actual cell division

toxicity to normal tissue that limits further dose escalation

Dose just below the DLT

period of lowest blood cell counts, after chemotherapy TTT