Chemotherapy

LEARNING OBJECTIVES

  • Define chemotherapy and types.

  • Describe the mode of action and limitations.

  • Identify the side effects of chemotherapy.

Chemotherapy: Treatment of cancer using specific chemical agents or drugs that are antineoplastics to kill tumor cells by interfering with cellular functions and reproduction.

  • Used to treat solid tumors as well as blood cancers.

  • Systemic chemotherapy is the main treatment for disseminated malignant disease.

Why chemo?

  • To maximize the death of malignant tumor cells.

  • To cure the client with cancer.

  • Control tumor growth when cure is not possible.

  • Extend lifespan and improve QOL.

Types of Chemo

Adjuvant chemo

  • Giving patients anti-cancer drugs after the primary tumor has been removed by surgery or radiotherapy and there is no evidence that cancer remains in the body.

  • The intent of adjuvant chemo is to attack microscopic cancer cells that may have remained after tumor removal.

Neoadjuvant (Primary) Chemo

  • Use of anti-cancer drugs as the main form of treatment or as a treatment prior to surgery or radiotherapy.

  • In some cases, the tumor may be so large that the surgery to remove it would destroy major organs or would be quite disfiguring. Primary chemo may reduce the tumor size, making it possible for a surgeon to perform a less traumatic operation.

Palliative chemo

  • Is given without curative intent

    • To control symptoms.

    • Decrease tumor load.

    • Increase life expectancy in a patient in whom cure is unlikely.

Mechanism of Action

  • Kills cells

  • Interfere with cell proliferation

  • Damage cell DNA

  • Prevent DNA repair in cell

Cancer chemotherapy and Cell cycle

  1. Cell-cycle non-specific agents: Cytotoxic in any phase of the cycle even on G0 phase and so are more effective against large slowly growing tumors.

    • ANKYLATING AGENTS - Cis-plating (platinol)

      • Works on:

        • Already formed DNA

        • Cross-linked strands

        • Prevents replication

      • Binds and crosslinks DNA → triggering apoptosis.

      • Treats a range of cancers e.g

        • Testicular, bladder, lung, stomach and ovarian cancers.

    • CYTOTOXIC ANTIBIOTICS

      • Interfere with nucleic acid synthesis.

      • Inhibit DNA and RNA synthesis

      • e.g Actinomycin - D

      • Inhibition of DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, prevents replication → inhibits Topo II.

  2. Cell-cycle specific agents: cytotoxic on all phases but not on cells out of the cycle (G0) and so are more effective against rapidly growing tumors. Work better in combination than alone.

    • ANTIMETABOLITES - Methotrexate (placental cancer)

      • Inhibits protein synthesis.

      • Interferes with DNA synthesis

      • Methotrexate is a mimic of folic acid

      • Inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydro folic acid (THF).

      • THF is a precursor for DNA purines and pyrimidines.

      • Reduction of coenzyme limits DNA synthesis.

    • PLANT ALKLOIDS

      • Inhibits M-phase

      • Arrests metaphase by binding to cell proteins.

      • Inhibit protein.

      • Inhibit RNA synthesis.

      • e.g Vincristin (Oncovin)

        • Drugs that disrupt the formation of mitotic spindles inhibit cell division.

  3. Cell-cycle phase specific: act on specific phases of the cycle.

Drug Resistance

Tumor cells may develop drug resistance.

Those that survive will have selective pressure for their survival and propagation.

Combination therapy regime may be required.

Mechanism of Drug Resistance

Cell Membrane Properties

  • The cell membrane is impermeable → chemo cannot enter the cell.

  • The drug is actively pumped out of the cell by the P-glycoprotein → cell efflux.

Drug inefficiency

  • The drug is not metabolized to an active form.

  • The drug is inactivated.

Affects Target

  • The drug target is increased e.g increased level of enzyme or gene amplification.

  • Mutation in a target protein decreases the affinity for the drug.

  • Alternative biochemical pathways are increased.

Cannot target DNA

  • There is a decrease in topoisomerase II and DNA breaks.

  • DNA damage is repaired.

Side Effects of Chemo

B - Bone marrow Suppression

  • Neutropenia

  • Leukopenia

  • Thrombocytopenia

  • Anemia

  • Fatigue

  • Risk for infection → Reduced WBCs

  • Risk for bleeding → reduced platelets

A - Alopecia

  • Form thin wispy pattern to total hair loss.

    • Hair regrows: Thicker, Wavier, Darker color

R - Retching

  • Emetic center triggered

  • Nausea

  • Anorexia

  • Diarrhea

  • Constipation

F - Fatigue

Mucosal Tissue:

  • Stomatitis

  • Ulcerating lesions on mucosa

  • Burning sensation with fluids

  • Pain to oral or esophageal mucosa

  • Nutrition to poor - no appetite

Neurological

  • Parastheisa

  • Motor weakness

  • Paralytic ileus → Paralysis of small intestine

Urinary

  • Hemorrhagic cytitis

  • Renal toxicity

  • Purines released during cell destruction converted to uric acid crystals → gout.

Chemotherapy treatment

  • Pre-hydration

  • Solution 150-200ml usually

  • Pre-med with anti-emetics