Drugs Used in the treatment of Cancer

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Drugs Used in the treatment of Cancer

• Pharmacology 49.222
• Bill Diehl-Jones RN, PhD
• Faculty of Nursing and Department of Zoology

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Agenda

• Zen Review
• What is cancer
• General goals in cancer treatment
• Targets of chemotherapy
• Targets of radiotherapy
• Breast cancer therapies
• Prostate cancer therapies

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Characteristics of Cancer Cells

• The problem
• Cancer cells divide rapidly (cell cycle is
  accelerated)
• They are immortal
• Cell-cell communication is altered
• They can disrupt normal, healthy tissues

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The Cell Cycle
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Anticancer Drugs

• Some Solutions
• Most cancer chemotherapies are designed to hit
  cell replication
• A problem
• This approach is non-specific
• Most cancer chemotherapies kill cancer cells only
  slightly faster than normal cells

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Targets of Anticancer Drugs
Inhibitors of DNA Synthesis (Mercaptopurine,
Methotrexate)
STOP
Inhibitors of DNA Function (Doxorubicin,
Cisplatin)
STOP
STOP
Inhibitors of DNA Replication (Cytochalasin,
Vincristine)
Protein
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The Goal of Cancer Treatments

• Curative
• Total irradication of cancer cells possible?
• The concept of log kill
• If 109 cells present, and tmt kills 99.999, then
  0.001 left
• This is a 5-log kill
• Palliative
• Alleviation of symptoms
• Avoidance of life-threatening toxicity

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Cell Cycle-Dependant vs. Cell-Cycle Independent
Drugs

• Some drugs kill cancer cells only at certain
  phases of the cell cycle
• Eg Cytochalsin
• Works only when a high ppn of cells are dividing
• Some drugs work throughout cell cycle
• Eg Cisplatin

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Some General Chemotherapy Concepts

• Most drug therapies are combination
• Eg for ALL
• POMP Prednisone, Oncovin, Methotrexate,
  Purethinol
• Most chemotherapeutics have very low Therapeutic
  Indices
• Some treatments themselves may induce tumors

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Breast Cancer Treatments/Therapies
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Hormonal Theory of Breast Cancer

• Reproductive risk factors include
• Early puberty, late menarche, short duration of
  breast feeding, nulliparity, delayed child birth
• Theory
• prolonged exposure to estrogen may initiate
  breast cancer

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Exposure to Estrogen-like Compounds Confers Risk
of Breast Cancer

• They may bind to same receptors, yield similar
  metabolites

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Mechanisms
Estrogen/Estrogen-like Molecules Induce
Cell-Proliferation Genes
Estrogen/Estrogen-Like Metabolites Form DNA
Mutations
OH, O
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DNA AdductsWhy are they problematic?

• Adducts may disrupt key regulatory pathways in
  ductal cells
• Eg p53, ras
• Adducts can cause gene mutations

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Many Breast Cancer Therapies Depend on Estrogen
Receptor Status
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Blocking Estrogen Receptors

• Principle drug is TAMOXIFEN
• Competes with estradiol for binding sites
• Works in ER cancers
• Often used in breast cancers which have
  metastasized to bone
• May cause pain in affected site a GOOD sign!
• May cause eye damage

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Aromatase Inhibitors

• A New Class of Breast Cancer Drugs
• NOT ER Dependant

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Estrogen from Two Sources May Initiate Breast
Cancer
Exogenous Estrogen
Androstenedione
Testosterone
AI
Aromatase
Estradiol
Estrone
Endogenous Estrogen Due to aromatase
overexpression
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Aromatase Inhibitors

• While Tamoxifen blocks a tumors abitlity to use
  estrogen, AIs reduce the amount of estrogen in
  the body
• Three AIs currently approved
• Anastrazole (Arimidex)
• Exestane (Aromasin)
• Letrozole (Femara)

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The Bottom Line

• A major study of AIs
• Breast cancer survivors taking letrozole after
  completing 5 years tamoxifen theraoy had
  significantly lower recurrence of breast cancers
  than women NOT on letrozole

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Prostate Cancer

• It doesnt matter who you are if you are male
  and live long enough, you WILL get prostate
  cancer
• Bill Jones Sr.

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How is Prostate Cancer Detected?

• DRE
• PSA

A combination is best
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Prostate Cancer Therapies

• Watch and wait
• Generally a slow-growing cancer
• Surgery
• Surgical excision, nerve-sparing (hopefully)
• Brachiitherapy
• Implantation of radioactive pellets

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A Cancer Case Study

• HPI
• A 25 yo male athlete presents with severe cough,
  SOB c/o a painful R. testicle
• O/E
• Non-encapsulated mass in testes masses detected
  in abdomen, lungs and brain
• Dx
• Metastatic testicular cancer (choriocarcinoma,
  40 embryonal, 1 teratoma

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Testicular Cancer Factoids

• Most common cancer in men 15 35
• 90 cure rate if detected early
• Method of detection
• Routine testicular palpation

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Treatment

• Surgical excision of testicle
• Surgery to remove 2 cancerous lesions on brain
• Chemotherapy
• 1 round of BEP (bleomycin, etoposide, platinol)
• 3 rounds of VIP (Ifostamide, etoposide, platinol)
• Period of treatment
• October December, 1996

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Can you name the patient?
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Lance Armstrong

• 6-time Tour de France winner (AFTER getting
  cancer)

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Responsiveness to Chemotherapy

• These Cancers Respond
• Hodgkins lymphoma
• ALL
• Choriocarcinoma
• Wilms tumor
• Testicular, other germ line cas

• These may respond
• Breast, ovarian, endometrial, myeloma, large
  intestine, esophageal CAs

• These do NOT respond
• Thyroid, Brain CA, liver, malignant melanoma,
  pancreatic, cervical