Treatment - Chemotherapy

Chemotherapy

• History of Chemotherapy
  • Mustard gas, a poison, was used in World War I (1914).  The soldiers who had cancer and were exposed to the gas showed improvement in their cancers.  These healing effects of mustard gas were discovered by accident and called “chemotherapy”  
  • Many changes have occurred in chemo
    • The types of drugs used
    • How the drugs are given to the patient
      • Intravenous [IV, injected in a vein]
      • Orally [pills, by mouth]
      • Catheter [through a tube sewn into the body when the veins cannot handle the drugs or when the amount of drugs is very large] 
    • The strength of the drugs [dosage]
    • The combinations of drugs
    • How often chemo is given [frequency]
    • How long the series of chemo treatments last (6 weeks, then a break for a few months) [duration]
  • Prior to the 1950s, treatment for the majority of cancers was limited to either surgery or the use of radiation

Chemotherapy today

• There are more than 100 different chemotherapy drugs
• The discovery of the use of methotrexate in curing a rare cancer marked the first time a cancer had been cured
• This led to the development of many of today’s common cancer treatments
  • The drugs are used in different proportions or amounts
  • The drugs are combined with other chemo drugs (chemo cocktail)
• The amount and type of chemo you receive is based on the
  • The type of cancer cells (histology)
  • The size of your tumor
  • Whether or not your cancer has spread (metastasized) 

How chemo works

• Cancer cells grow and duplicate quickly.
• Chemo uses drugs that kill cells or slow down their duplication.
• In general, chemotherapy drugs affect the DNA of the cells by interfering with cell duplication.
• Chemo drugs are poisons that breaks up the DNA so that it cannot make new cells

Why both cancer and healthy body cells are affected by chemo

• Chemo drugs affect the DNA of both the cancerous and healthy cells
• The healthy cells that are particularly susceptible to chemo are by cells that multiply quickly:
  • The skin (including body, facial, and head hair)
  • The digestive system (gastrointestinal tract)
  • The bone marrow (that makes red and white blood cells)

Goals of chemotherapy

• Cure
• Control - extend length and quality of life when hope of cure is not realistic
• Palliation – ease symptoms/ improve comfort

Purpose(s) for Chemotherapy

• Shrink the size of a tumor before surgery or radiation
• Kill or poison cancer cells when surgery is not an option (to destroy or slow the growth of cancer cells)
• Kill or poison any remaining cancer cells that were not removed during surgery (to stop cancer from spreading)
• Relieve cancer pain or other symptoms

Why you may receive a different combination and dosage of chemo drugs than the patient sitting next to you

• The most common reason is because your cancer is different from the patient sitting next to you (you have a different type of breast cancer)
• Another reason is that you may have had severe side effects and they are using a different combination of drugs (cocktail) to see if you react better to the treatment
• Another reason is that one of you may be on a clinical trial that is using a drug combination that may or may not be better than standard treatment for your type of cancer.

Chemotherapy is the treatment of choice for:

• Leukemias, lymphomas (blood forming cells)
• Solid tumors that have metastasized
• Cancers with high potential of spread/ recurrence

How does it work?

• Attack cells when they are dividing (cancer cells divide much more often than do normal, healthy cells)
• Damage genetic material inside the cell that allows the cell to divide and reproduce
• Block chemicals that the cell needs to enable it to divide and reproduce

Types of chemotherapy

• Standard therapies used alone or in combination with newer therapies and other treatments
  • Alkylating agents
  • Interferes with DNA replication (cross link DNA strands) and inhibits cancer cell growth
  • Most agents are cell cycle nonspecific
  • Such as:  Busulfan (Myleran), Cyclophosphamide, Temozolamide (Temodar)
• Antimetabolites
  • Drugs that interfere with one or more enzymes or their reactions that are necessary for DNA synthesis.
  • They affect DNA synthesis by acting as a substitute to the actual metabolites that would be used in the normal metabolism
  • Inhibit protein synthesis, substitute metabolites, or structural analogues during DNA synthesis and inhibit DNA synthesis
  • For example, antifolates interfere with the use of folic acid
• Most are cell cycle/phase specific
  • Such as: 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), Capecitabine (Xeloda), Gemcitabine)
• Anti-tumor antibiotics
  • A type of anticancer drug that blocks cell growth by interfering with DNA, the genetic material in cells
  • Interferes with nucleic acid synthesis and function. Inhibit RNA synthesis
  • Also called anticancer antibiotic and antineoplastic antibiotic
  • Most agents are cell cycle nonspecific
  • Such as:  Dactinomycin (Cosmegen), Bleomycin, Daunorubicin (Cerubidine, Rubidomycin) and Doxorubicin (Adriamycin PFS, Adriamycin RDF)
• Topoisomerase inhibitors
  • Enzymes that participate in the overwinding or underwinding of DNA. ... In order to prevent and correct these types of topological problems caused by the double helix
  • Chemical compounds that block the action of topoisomerases (topoisomerase I and II), which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle
  • Such as:  Etoposide, Irinotecan (Camptosar), Topotecan (Hycamtin)
• Mitotic inhibitors
  • A type of drug that blocks cell growth by stopping mitosis (cell division); also called antimitotic agent
  • Bind with microtubular proteins, crystallize the mitotic spindle, and result in metaphase arrest
  • Phase cycle specific
  • Such as:  Docetaxel (Taxotere), Eribulin (Halaven), Ixabepilone (Ixempra), Paclitaxel (Taxol), Vinblastine

Methods of Administration

• Oral
• Intravenous (IV)
• Catheter, port, pump
• You sit in a room alone or with other patients who are also getting chemo
  • Your family or friends can come sit with you while you receive the treatments
  • You may want to bring a blanket because if your treatment lasts for a few hours, you may get cold (the liquid in the IV is cold)
  • You may want to have a glass with some ice chips to suck on
  • You may want to drink a mild tea, like ginger tea to help reduce the upset stomach
  • If you are diabetic, you need to bring a healthy snack or drink so that your blood sugar doesn’t get too low while you are in treatment
• Injection
• Intrathecal
• Intraperitoneal (IP)
• Intra-arterial (IA)
• Topical

Classifications of Chemotherapy

• Cell cycle specific agents (phase specific)
  • Major effects exerted only when cells in a specific part of the cell cycle
• Cell cycle nonspecific agents
  • Effects are exerted on cells at any phase

The Cell Cycle and Phase-Specific Chemo

• Many chemotherapy drugs are designed to attack the cells during a specific phase of cell reproduction, such as:
  • One drug may target the cell ONLY during the G1 phase
  • Another drug may target the cell ONLY during the S phase

Reference: https://www.ncbi.nlm.nih.gov/books/NBK26869/figure/A3171/?report=objectonly

• Cell Phase:
  • G1 phase (pre DNA) 8-48 hrs
    • RNA and protein synthesis actively preparing for DNA synthesis
  • S phase (DNA synthesis) 10-30 hrs
    • DNA doubles in preparation for mitosis
  • G2 phase (pre-mitotic phase) 1-12 hrs
    • DNA synthesis discontinues and prepares for cell division
  • M phase (mitosis) 1 hr
    • Spindle formation, separation of chromosomes and cell division
  • G0 phase (resting phase)
    • Cell is no longer dividing and highly resistant to chemotherapy during this phase