Cancer

...

Anticancer Drugs: 4 major classes

Cytotoxic: kill cells directly
Hormones and hormonal antagonists
Biologic response modifiers
Targeted drugs

...

-Leading cause of Death
-565,650 Americans died from cancer in 2008
-Children ages 1-14, cancer is leading cause of death
-Women: breast, lung colorectal
-Men: prostate, lung and colorectal
-3 modalities for treatment: surgery, radiation and drug therapy

Challenges to Chemotherapy

-Toxicity to normal cells
-Cure Requires 100% cell kill
-Absence of Early Detection (exception pap smear)
-Solid Tumors Respons Poorly
-Drug Resistance

Cytotoxic

Cytotoxic most common form of treatment.
-Began in 1942 with nitrogen mustards
-Many advances
-High cure rate with Hodgkin's disease and some leukemia

Intermittent Chemotherapy

When cytotoxic anticancer drugs are administered intermittently, normal cells have time to repopulate between rounds of therapy

Combination Chemotherapy

-Suppression of Drug Resistance
-Increased Cancer Cell Kill
-Reduced injury to normal cells

Optimizing Dosing Schedules

Drugs must also be administered according to schedules that maximize beneficial benefits

Cytotoxic Anticancer Drugs

Alkylating agents
-Nitrogen mustards, nitrosourease and other compounds
-Interact with DNA
-Reaction my occur at any time in the cell cycle
-Development of resistance is common
-Highly toxic: Neutropenia, thrombocytopenia, bone marrow suppression

Regional Drug Delivery

Intra-arterial delivery: treat solid tumors. High concentration of drug close to the tumor
Intrathecal delivery: used to bypass the blood brain barrier

Major Toxicities

Bone Marrow Suppression
-Neutropenia
-Thrombocytopenia
-Anemia
Digestive Tract Injury
-Stomatitis - inflammation of the oral mucosa
-Diarrhea
-Nausea and Vomiting
Other
-Alopecia
-Reproductive Toxicity
-hyperuricemia

Mitotic Inhibitors

Act during M phase to prevent cell division

Platinum Compounds: Cisplatin

-kills cells by forming cross links between strands of DNA.
-Approved for metastatic testicular and ovarian cancer. Also for advanced bladder cancer
-Off label for lung cancer and head/neck cancer
-Dose limiting toxicity is renal damage
-Required excessiv

Antimetabolites

-Analogs of natural metabolites
-Able to disrupt metabolic processes
-Effective only against cells that are active participants in the cell life
-Folic Acid Analogs: Methotrexate
-Pyrimidine analogs: Fluorouracil (treatment for solid tumors)
-Purine Analo

Antitumor Antibiotics

-Only used to treat cancer : not infection
-Injure cells through direct interaction with DNA
-Poor GI absorption
-IV administration
-Causes severe bone marrow suppression and may lead to cardiotoxicity. ACE inhibitors may improve the symptoms of Cardiomyo

Mitotic Inhibitor: Vinca Alkaloids (Oncovin)

-Bone marrow sparing
-Ideal for combination chemotherapy including Hodgkin's, non-Hodgkins, leukemia, kaposi sarcoma, breast cancer and bladder cancer.
-Toxicity: peripheral neuropathy

Mitotic Inhibitor: Taxanes (Taxol)

-First line therapy for advanced ovarian cancer and non-small cell lung cancer.
-Toxicity: hypotension, angioedema, urticaria

Glucocorticoids

-Used in combination with other agents to treat cancers arising from lymphoid tissue
-Directly toxic
-Minimal toxicity
-Long term side effects

Drugs for Breast Cancer: Anti-estrogens

Tamoxifen: blocks estrogen receptors
Raloxifen

Drugs for Prostate Cancer

-Standard treatment for advanced prostate cancer is androgen deprivation
-Lowering testosterone production
-Blocking testosterone receptors
-Does not cure disease, but can slow progression
-Side effects hot flushes, impotence, reduced libido, decreased mu

Drugs for Breast Cancer: Trastuzumab (Herceptin)

-IV treatment of metastatic breast cancer to inhibit cell proliferation and promote antibody-dependent cell death.
-cardiotoxicity

Drugs for Breast Cancer: Aromatase Inhibitors

Anastrozole (Arimidex): first line oral treatment for early or advanced ER positive breast cancer. Drug deprives breast cancer cells of estrogen

Drugs for Breast Cancer

Anti-estrogens
Aromatase inhibitors
Trastuzumab (Herceptin)
Cytotoxic Drugs

Targeted Anticancer Drugs

-Designed to bind with specific molecules to alter tumor growth
-Causes little or not injury to normal cells
-Serious side effects