Chemotherapy

 

 

Classification

Chemotherapy agents (based on their chemotherapeutic effects on the cell cycle), are either:

  • Cell-cycle-specific or
  • Cell-cycle-non-specific

 

Chemotherapeutic Effects on The Cell Cycle:

CELL CYCLE SPECIFIC

CELL CYCLE NON-SPECIFIC

Most effective during a specific phase of the cell cycle

Effective regardless of the cell cycle phase

Greatest effect on actively dividing cells

Work in any phase

Not active in G0 phase

Active in G0 phase

Greatest action in divided doses or as continuous infusion

Greatest action when administered as a bolus

Cytotoxic effects occur when cell repair or division attempted

Cytotoxic effects occur when cell division attempted

 

Chemotherapy agents are classified according to their:

  • Chemical structure
  • Biological source
  • Physiological effect on the cell cycle

 

Overall Summary of Chemotherapy Mechanisms of Action:

Mechanism of Action Drug

Damage DNA or interfere with DNA replication

Alkylating agents

Antitumor antibiotics

Antimetabolites

Nitrosureas

 

Cause a cell cycle phase arrest

Plant alkaloids

Interfere with protein synthesis

Hormonal agents

Interfere with blood vessel development to tumor

Antiangiogenic agents

Biological response modifiers

 interleukins, interferons

 

Classification of Chemotherapy:

Drug Classification

Mechanism of Action

Alkylating agents
  • Cell-cycle-non-specific
  • Break DNA helix strand, interfering with DNA replication
  • Most active in G0 phase

Antitumour Antibiotics
  • Cell-cycle-non-specific
  • Bind to DNA and interfere with further replication of DNA and transcription of RNA

Antimetabolites
  • Cell-cycle-specific to S phase
  • Resemble essential metabolic elements needed for cell growth
  • Inhibits RNA and DNA synthesis

Plant Alkaloids
  • Cell-cycle-specific to M phase
  • Cause a cell cycle phase arrest

Hormones
  • Cell-cycle-non-specific
  • Act in a variety of ways
  • Mechanism of action not fully understood
  • May have “direct lytic action” on cells in certain diseases (eg corticosteroids in leukemia, lymphoma)
  • Interfere with protein synthesis

Antiangiogenic Agents
  • Interfere with blood vessel development to tumor

Miscellaneous Agents
  • Variety of agents that do not fit into any category
  • Mechanism of action not fully understood
  • Eg. l’aparaginase, hydroxyurea

 

Principles of Combination Chemotherapy

  • Two or more agents have greater response than when used alone.
  • Act in different phases of cell cycle.
  • Vary toxicities.
  • Each drug has independent action.
  • Synergistic effects to overcome drug resistance

 

 

 

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