RS Pharm CH 22 Chemotherapy Drugs

Combination monoclonal antibody drugs

§Containing a monoclonal antibody drug and radioactive isotope used to treat non-Hodgkin lymphoma •Bexxar •Tositumomab, iodine-131 •Zevalin •Ibritumomab, indium-111, yttrium-90 §Containing a monoclonal antibody drug and a cytotoxic drug •Kadcyla •Ado-trastuzumab •Emtansine

Taxane chemotherapy drugs

§Disrupt the microtubular network in the cytoplasm of the cell during cell division §As the cell divides: •Centrioles migrate to either end of the cell. •Microtubules form spindle fibers that radiate from the centrioles and connect the chromosomes. §Allow the microtubules to form, but the microtubules do not function properly §Cabazitaxel (Jevtana) §Docetaxel (Taxotere) §Paclitaxel (Onxol)

Alkylating Chemotherapy Drugs: Nitrosourea chemotherapy drugs

§Insert an alkyl group into both DNA and RNA §DNA and RNA cannot be produced. §Cancer cell cannot divide. §These drugs inhibit enzymes within the cell •Carmustine (BiCNU, Gliadel) •Lomustine (CeeNU) •Streptozocin (Zanosar)

Focus on Health Care: Adjuvant therapy

§Refers to chemotherapy (or radiation therapy) that is given to cancer patients after they have had surgery to remove a tumor §Purpose is to aid in eradicating any remaining tumor cells. §Phrase is taken from a Latin word meaning aiding. •Remission occurs when cancer cells stop actively reproducing. •Cancer patients §Some experience a complete remission following chemotherapy. §Others have a partial remission. §Some actually experience tumor growth while being treated with chemotherapy.

Podophyllotoxin chemotherapy drugs

§Semisynthetic drugs created from a toxin found in the fleshy root of the Mayapple (Podophyllum peltatum) §Keep new DNA from being formed §Break strands of DNA §Cause DNA strands to abnormally cross-link to each other Drug list: §Etoposide (Etopophos, VePesid) §Teniposide (Vumon)

Granulocyte colony-stimulating factor drugs

§Substance that is normally produced by the body §Stimulate the production of neutrophils §Used to treat decreased levels of neutrophils that occur after chemotherapy or bone marrow transplantation •White blood cells that kill bacteria and fight infection •Belong to the white blood cells known as granulocytes §These drugs are produced by recombinant DNA technology by inserting the human gene that produced G-CSF into rapidly dividing bacteria or yeast cells •Filgrastim (Neupogen) •Pegfilgrastim (Neulasta) •Sargramostim (Leukine)

Introduction: Chemotherapy Drugs

•A neoplasm is a new growth of cells, may be: §Benign §Malignant •All malignant neoplasms are classified as cancer. •As cancerous cells invade tissues and organs, normal function is compromised. §Sometimes impaired to the point of death, unless treated with: •Surgery •Radiation •Chemotherapy drugs

Did You Know? chemotherapy drugs

•According to Pharmacy Times, more health care dollars were spent in 2013 on chemotherapy drugs than on any other drugs. §The cost for chemotherapy drugs that year was nearly $28 billion. •Chemotherapy drugs also topped the spending list in 2012.

Platinum Chemotherapy Drugs

•Contain the precious metal platinum •Create cross-links in DNA strands •Used to treat many different types of cancer •Carboplatin (Paraplatin) •Cisplatin •Oxaliplatin (Eloxatin)

Chemotherapy Enzyme Drugs

•Enzymes that break down the amino acid asparagine •Humans can synthesize their own supply of asparagine, and so asparagine is not one of the eight essential amino acids that the body needs to produce protein. •Leukemia cells, however, cannot synthesize their own asparagine. •By breaking down asparagine, the cancer cell cannot use it to build protein. §Cannot divide •Asparaginase (Elspar) •Pegaspargase (Oncaspar)

In Depth : erythropoietin

•Epoetin alfa (Epogen) has a therapeutic effect similar to that of the hormone erythropoietin that is secreted by the kidneys in response to anemia. •Erythropoietin increases the rate at which red blood cells are produced in bone marrow. §This effect is decreased in cancer patients. •Chemotherapy drugs and radiation therapy decrease the ability of the bone marrow to produce red blood cells.

Demethylating Chemotherapy Drugs

•Inhibit the enzyme methyltransferase §Enzyme normally transfers a methyl group and inserts it into DNA (a process known as methylation) during cell division. §Because the DNA lacks a methyl group, the cell cannot divide. •Particularly affects rapidly dividing cancer cells •Have a direct cytotoxic effect on abnormal blood cells in the bone marrow •Treat leukemia or lymphoma •Azacitidine (Vidaza) •Decitabine (Dacogen)

Did You Know? Tamoxifen

•Tamoxifen is also given prohphylactically (preventing the spread or occurrence of disease or infection) to women who are at high risk for developing breast cancer before they develop breast cancer.

In Depth: Targeted chemotherapy

•Targeted chemotherapy §Drugs that block the growth of cancer cells by targeting and interfering with specific molecules on the cancer cell §Examples •Selective estrogen receptor modulator (SERM) chemotherapy drugs •Monoclonal antibody drugs

Did You Know? Schedule III drug dronabinol (Marinol)

•The Latin name for the marijuana plant is Cannabis sativa, and the active components in marijuana that produce physical and psychological effects are known as cannabinoids. •The antiemetic, Schedule III drug dronabinol (Marinol) is a cannabinoid, and it is also known by its chemical name delta-9-tetrahydrocannabinol, abbreviated delta-9-THC, or just THC. •In addition to its use as an antiemetic drug, dronabinol (Marinol) is also used as an appetite stimulant for patients with AIDS. •Nabilone is a Schedule II synthetic cannabinoid drug.

Did You Know? tretinoin

•The generic drug tretinoin is also available as a topical drug. •As the trade name drug Retin-A, it is used topically to treat acne vulgaris. •As the trade name drug Renova, it is used topically to treat skin wrinkles.

Did You Know? pyrimidine analog chemotherapy drug cytarabine

•The pyrimidine analog chemotherapy drug cytarabine was developed from a substance found in Caribbean sea sponges.

epirubicin (Ellence)

. Most chemotherapy drugs are clear, but epirubicin (Ellence) has a unique red color. Epirubicin is only used to treat breast cancer. The chemotherapy drug doxorubicin (Adriamycin) also has that red color.

Chemical structures of folic acid and methotrexate

Folic acid blocker chemotherapy drugs, such as methotrexate, are very similar in their chemical structure to that of folic acid, the B vitamin whose action they block. see pic

Preparing a chemotherapy drug

In preparing chemotherapy drugs, pharmacists must maintain sterile technique to protect the immunocompromised cancer patient from infection. Working under a laminar flow hood maintains a sterile work environment, as the surrounding air is constantly passed through a filter to remove all bacteria, viruses, etc. This pharmacist is wearing gloves and a gown to maintain a sterile environment, and also to protect her skin and clothing from exposure to the chemotherapy drug. The Occupational Safety and Health Administration (OSHA), a federal government agency, issues guidelines for minimizing exposure to all types of hazardous substances, including chemotherapy drugs. see pic

Filgrastim (Neupogen)

The generic name filgrastim reflects the therapeutic effect of this drug, which is granulocyte stimulation. Filgrastim (Neupogen) was the first of the granulocyte colony-stimulating factor drugs to be introduced. It, like all of the granulocyte colony-stimulating factor drugs, is created using recombinant DNA technology. see pic

docetaxel and paclitaxel

The taxane chemotherapy drugs docetaxel and paclitaxel are commonly used to treat breast cancer and are included in many chemotherapy protocols for breast cancer

Melphalan (Alkeran)

This chemotherapy drug is only used to treat two kinds of cancer: ovarian cancer and multiple myeloma, which is a cancer of the plasma cells that produce the antibodies in the blood.

Hydroxyurea

This chemotherapy drug is used to treat a variety of different and unrelated types of cancer, including leukemia, melanoma, cancer of the ovary, and squamous cell carcinoma of the skin of the head and neck.

Bicalutamide (Casodex)

This hormonal chemotherapy drug blocks the effect of testosterone, and so it is useful in treating cancer of the prostate gland in men.

Vinca

Vinblastine, vincristine, and vinorelbine are extracted from the Madagascar rosy periwinkle plant. The scientific name for this common evergreen ground cover is Vinca rosea. The vinat the beginning of these generic drug names reflects the plant's name. It takes over 6 tons of periwinkle leaves to produce 1 ounce of the drug. see pic

Alkylation

§A chemical reaction in which an alkyl group from the chemotherapy drug is substituted for a hydrogen molecule in DNA and/or RNA §Causes abnormal cross-linking in the DNA strands •Cancer cell cannot divide.

Progestin hormone chemotherapy drugs

§Act in a similar way to that of the female hormone progesterone, produced by the corpus luteum of the ovary §Used to treat breast cancer in females because they contain a different female hormone than the estradiol that breast cancer needs to grow Drug list: §Medroxyprogesterone (Depo-Provera, Provera) §Megestrol (Megace)

Estrogen hormone chemotherapy drugs

§Act in a way similar to that of the main female hormone estradiol, produced by follicles of the ovary §Used to provide palliative (relieving pain) treatment for: •Advanced breast cancer •Advanced prostate cancer §Provide relief from symptoms but not intended to cure cancer §Conjugated estrogens (Premarin) §Esterified estrogens (Menest) §Estradiol (Delestrogen, Estrace) §Raloxifene (Evista)

Androgen hormone chemotherapy drugs

§Act in a way similar to that of the main mail (androgen) hormone testosterone, produced by the testicles §Used to treat breast cancer in females because they create a male hormone environment, which is opposite from what the breast cancer cell needs to grow §These are Schedule III drugs. •Fluoxymesterone (Androxy) •Methyltestosterone (Testred, Virilon) •Testosterone (Delatestryl)

Topoisomerase inhibitor chemotherapy drugs

§Affect the enzyme topoisomerase •Normally relieves the twisting stress on the spiral strands of DNA •Creates a break in a single strand so that the strand can separate and be copied during cell division •Break is later repaired in the process. §Bind to the enzyme topoisomerase •Prevent the enzyme from creating the initial break in the DNA strand •The cancer cell cannot divide. Drug list: §Irinotecan (Camptosar) §Mitoxantrone (Novantrone) §Topotecam (Hycamtin)

•Other mitosis inhibitor chemotherapy drugs

§Belong to the group of epothilone drugs §Used to treat breast cancer §Eribulin (Halaven) §Ixabepilone (Ixempra)

Selective estrogen receptor modulator chemotherapy drugs

§Bind to and block receptors in breast tissue that are normally stimulated by estradiol §With the effect of estradiol blocked, breast cancer cannot grow. Drug list: §Fulvestrant (Faslodex) §Tamoxifen §Toremifene (Fareston)

Anti-androgen hormone chemotherapy drugs

§Bind to and block receptors in the prostate gland tissue that normally stimulated by testosterone §With the effect of testosterone blocked, the prostate gland cancer cannot grow. Drug list: §Bicalutamide (Casodex) §Enzalutamide (Xtandi) §Flutamide §Nilutamide (Nilandron)

Aromatase inhibitor chemotherapy drugs

§During menopause, the level of estradiol secreted by the ovaries declines. •Main source of estradiol in postmenopausal women is adrogens from the adrenal gland. •Converted by the enzyme aromatase to estrone and then estradiol §Bind to the enzyme aromatase and hinder its action •Without estradiol, the breast cancer cells cannot grow §Some, but not all, of these drugs are used to treat cancer of the prostate gland in men, because they produce the opposite hormonal environment from what the prostate gland cancer needs to grow. §Anastrozole (Arimidex) §Letrozole (Femara) §Exemestane (Aromasin) §Testolactone

Antimetabolite Chemotherapy Drugs: Folic acid blocker chemotherapy drugs

§Folic acid •B vitamin whose metabolite is important in DNA production in the cell §Act as antagonists §Compete with folic acid for the same enzyme, normally changes folic acid into the metabolite that carries purine to a forming DNA molecule §Without the folic acid metabolite •Purine is not available. •DNA cannot be produced. •The cancer cell cannot divide. §These drugs are used to treat many different types of cancer §Methotrexate (Trexall) §Pemetrexed (Alimta) §Pralatrexate (Folotyn)

Alkylating Chemotherapy Drugs: Other alkylating chemotherapy drugs

§Insert an alkyl group into the DNA §Also have other effects that prevent the cancer cell from dividing Drug list: §Altretamine (Hexalen) §Bendamustine (Treanda) §Busulfan (Myleran) §Dacarbazine (DTIC-Dome) §Thiotepa (Thioplex)

Alkylating Chemotherapy Drugs: Nitrogen mustard chemotherapy drugs

§Insert an alkyl group into the DNA §Causes cross-linking to occur in the strands of DNA §DNA cannot be produced. §Cancer cell cannot divide. Drug list: §Chlorambucil (Leukeran) §Cyclophosphamide §Estramustine (Emcyt) §Ifosfamide (Ifex) §Mechlorethamine (Mustargen) §Melphalan (Alkeran)

Vinca alkaloid chemotherapy drugs

§Interfere with: •Production of DNA and RNA •Cellular metabolism •Production of the energy needed to complete cell division §Bind to tubulin in the microtubules Drug list: §Vinblastine (Velban) §Vincristine (Vincasar) §Vinorelbine (Navelbine)

Antimetabolite Chemotherapy Drugs: Purine analog chemotherapy drugs

§Purine •A molecule that forms the based upon which adenine and guanine are built. •Two substances are important components of the DNA molecule in each cell. §Purine analog •Takes the place of the purine base structure •Normal metabolites (adenine, guanine) cannot be built. •DNA cannot be produced. •Cancer cell cannot divide. §These drugs are used to treat different types of cancers. §Cladribine (Leustatin) §Clofarabine (Clolar) §Fludarabine (Fludara) §Mercaptopurine (Purinethol) §Pentostatin (Nipent) §Thioguanine (Tabloid)

Antimetabolite Chemotherapy Drugs: Pyrimidine analog chemotherapy drugs

§Pyrimidine •A molecule that forms the base upon which cytosine, thymine, and uracil are built •Important components of DNA molecule §Take the place of the pyrimidine base structure §Normal metabolites (cytosine, thymine, uracil) cannot be built. §DNA cannot be produced. §Cancer cell cannot divide. §These drugs are used to treat many different types of cancer. §Capecitabine (Xeloda) §Cytarabine (DepoCyt, Tarabine) §Floxuridine (FUDR) §Fluorouracil (Adrucil) §Gemcitabine (Gemzar)

Cytoprotective drugs

§Some chemotherapy drugs are known to be toxic to particular organs of the body. §When a patient receives a chemotherapy drug that is known to be toxic to a particular organ, the patient is also given a drug to protect that organ from toxicity. §These drugs exert a cytoprotective effect that protects the cells of that organ against the toxic side effects of a specific chemotherapy drug. §Amifostine (Ethyol) •Protects the kidney from toxicity due to cisplatin and cyclophosphamide §Dexrazoxane (Zinecard) •Protects the heart from toxicity due to doxorubicin and epirubicin §Leucovorin (Wellcovorin) •Protects against toxicity due to methotrexate or fluorouracil §Levoleucovorin (Fusilev) •Protects against toxicity due to methotrexate or fluorouracil §Mesna (Mesnex) •Protects the bladder from toxicity due to ifosfamide §Sodium thiosulfate •Protects the kidneys from toxicity due to platinum chemotherapy drugs

Gonadotropin-releasing hormone chemotherapy drugs

§Synthetic reproduction (analog) of the body's own gonadotropin-releasing hormone (GnRH) •Normally produced in the hypothalamus •Action causes the testes in men to produce testosterone. •Action causes the ovaries in women to produce estradiol and progesterone. §Compete with GnRH and block GnRH receptors on the anterior pituitary gland Anterior pituitary gland is not stimulated to secrete luteinizing hormone. •The testes do not produce testosterone. -Without testosterone, prostate gland cancer cannot grow. •Ovaries do not produce estradiol or progesterone. -Without estradiol or progesterone, breast and ovarian cancers cannot grow. Drug list: §Goserelin (Zoladex) §Histrelin (Vantas) §Leuprolide (Eligard, Lupron) §Triptorelin (Trelstar)

Focus on Health Care: Failed chemotherapy

§When tumor size increases despite chemotherapy §New metastatic lesions appear despite chemotherapy. §New combination of the chemotherapy drugs may be tried.

Antimetabolite Chemotherapy Drugs

•Act against metabolites, important byproducts produced from other substances in the cell during the process of metabolism •Active in the production of cellular DNA •Take the place of an important metabolite •Block an enzyme that produces an important metabolite •Target rapidly dividing cells, such as cancer cells, that have a high rate of metabolism

Mitosis Inhibitor Chemotherapy Drugs

•Act at very specific times during the early stages of mitosis •Affect dividing cells and keep them from completing the process of cell division (mitosis) •Have their greatest effect on cells that divide often --Effect is felt more on cancer cells than on normal cells.

Did You Know? thalidomide

•After the drug thalidomide was used to treat morning sickness in pregnant women in Europe and caused the severe birth defect of phocomelia ("seal limbs") in their babies, it was withdrawn from the market. •It would have become an obscure footnote in medical history but, in 1997, it was discovered to be useful in treating cancer.

Miscellaneous Chemotherapy Drugs

•Arsenic (Trisenox) •BCG live (TheraCys) •Bortezomib (Velcade) •Denileukin diftitox (Ontak) •Hydroxyurea (Droxia, Hydrea) •Mitotane (Lysodren) •Procarbazine (Matulane) •Romidepsin (Istodax) •Temozolomide (Temodar) •Vorinostat (Zolinza)

In Depth: mitosis

•As a cell divides (mitosis), it goes through certain stages. §The chromosomes in the nucleus divide. §Microtubules (spindle fibers) migrate to either end of the cell, pulling the chromosomes with them. •Align the "parent" and "daughter" chromosomes across the diameter of the cell in a single line §Some of the "parent" chromosomes and some of the "daughter" chromosomes are pulled by the microtubules to opposite ends of the cell. §Cytoplasm of the cell splits to form two separate cells. •Microtubules play a prominent role in directing the location of the chromosomes during cell division.

Did You Know? Asparaginase

•Asparaginase is derived from the common intestinal bacterium Escherichia coli (E. coli) that causes most urinary tract infections. •Cancer patients who are hypersensitive to asparaginase can be treated with pegaspargase, a modified form of asparaginase that contains polyethylene glycol (PEG).

Did You Know? BCG

•BCG live is a weakened, but live strain of the bacterium (bacille Calmette-Guérin) that causes tuberculosis in cows. •A different form of BCG is given as a vaccine to stimulate the body to make antibodies against the bacterium that causes tuberculosis in humans.

Kinase Inhibitor Chemotherapy Drugs

•Block kinase enzymes that act on amino acid molecules by adding a side molecule of phosphate •Inhibit action so the cancer cell cannot divide Drug list: •Axitinib (Inlyta) •Bosutinib (Bosulif) •Cabozantinib (Cometriq) •Crizotinib (Xalkori) •Dabrafenib (Tafinlar) •Dasatinib (Sprycel) •Erlotinib (Tarceva) •Everolimus (Afinitor, Zortress) •Gefitinib (Iressa) •Ibrutinib (Imbruvica) •Imatinib (Gleevec) •Lapatinib (Tykerb) •Nilotinib (Tasigna) •Pazopanib (Votrient) •Regorafenib (Stivarga) •Sorafenib (Nexavar) •Sunitinib (Sutent) •Temsirolimus (Torisel) •Trametinib (Mekinist) •Vemurafenib (Zelboraf)

Hormone Chemotherapy Drugs

•Certain cancers need hormones to grow. §Cancers that arise from tissues that are influenced by: •Male sex hormone testosterone •Female sex hormones •Cancers have receptors on the surface of their cells for those hormones. §Growth of these cancers is stimulated by those hormones. •Actions of chemotherapy drugs §Block the effect of those hormone §Surround the cancer cells with a hormone that has the opposite hormonal effect

Antiemetic Drugs Used with Chemotherapy

•Chemotherapy drugs §Kill rapidly dividing cancer cells §Also affect the rapidly dividing cells in the mucous membrane of the GI tract, causing irritation §Directly stimulate the vomiting center in the brain §Some chemotherapy drugs cause the release of serotonin in the small intestine, which stimulates the vomiting reflex •Nausea and vomiting §Occur as a result of chemotherapy §Can be so severe and prolonged that, without antiemetic drugs, the patient might elect to discontinue life-saving chemotherapy •Antiemetic drugs are often given prophylactically prior to beginning chemotherapy. •These drugs, many of which block serotonin, are used specifically to treat the nausea and vomiting associated with chemotherapy. Drug list: •Aprepitant (Emend) •Dolasetron (Anzemet) •Dronabinol (Marinol) •Fosaprepitant •Granisetron (Kytril) •Nabilone (Cesamet) •Ondansetron (Zofran) •Palonosetron (Aloxi)

Drugs Used to Protect Against Chemotherapy Toxicity

•Chemotherapy drugs target rapidly dividing cancer cells. •Side effects are also felt in other areas where cells normally divide rapidly. --Mucous membranes lining the mouth --Mucous membranes lining the intestine --Bone marrow •These drugs are used to treat oral mucositis and dry mouth caused by chemotherapy drugs or radiation therapy. §Amifostine (Ethyol) §Palifermin (Kepivance) §Pilocarpine (Salagen) •These drugs are used to stimulate red blood cells production to treat anemia resulting from the cancer itself, chemotherapy drugs, or radiation therapy. §Darbepoetin alfa (Aranesp) §Epoetin alfa (Epogen, Procrit) •These bone resorption inhibitor drugs are used to treat elevated levels of calcium caused by cancer and bone metastases. §Gallium nitrate (Ganite) §Ibandronate (Boniva) §Pamidronate (Aredia) §Zoledronic acid (Zometa)

Monoclonal Antibody Drugs

•Created using recombinant DNA technology §Process takes human antibodies and modifies them §Selectively bind to specific antigens on the surface of cancer cells •As monoclonal antibody combines with the antigen, it destroys the cancer cell. Drug list: •Alemtuzumab (Campath) •Bevacizumab (Avastin) •Cetuximab (Erbitux) •Ipilimumab (Yervoy) •Obinutuzumab (Gazyva) •Ofatumumab (Arzerra) •Panitumumab (Vectibix) •Rituximab (Rituxan) •Trastuzumab (Herceptin)

Corticosteroid Drugs

•Derived from the anti-inflammatory hormone cortisol •Given to decrease the tissue inflammation caused by chemotherapy drugs •Act directly to suppress the production of excessive WBCs in patients with leukemia or lymphoma •Used to treat the anemia caused by chemotherapy drugs

Drug Alert: Hormone Therapies

•Do not confuse hormone chemotherapy drugs with hormone replacement therapy. •Hormone replacement therapy uses a female hormone drug and is only used to treat women in menopause. •In contrast, hormone chemotherapy drugs use a male hormone to treat a cancer that only occurs in females or a female hormone to treat a cancer that only occurs in males.

Focus on Health Care: chemotherapy drugs or antineoplastic drugs

•Drugs used to treat cancers or malignant neoplasms are know as chemotherapy drugs or antineoplastic drugs. •Chemotherapy drugs are most effective when initiated during the early stages of cancer when there are fewer cancer cells present in the body. •Most chemotherapy drugs exert their effect against rapidly dividing cancer cells. §However some normal cells in the body also divide rapidly. •Cells lining the GI tract •Hair cells •Blood cells §Greatly affected by chemotherapy •Inflammation of the mouth and GI tract •Loss of hair •Decreased number of RBCs and WBCs

Focus on Health Care: vitamin D

•In 2005, ABC World News Tonight reported that researchers had found that 1,000 mg of vitamin D per day could prevent cancer of the breast, ovaries, and uterus in women and cancer of the prostate gland in men. •In 2007, the same television show reported that a vitamin D deficiency allowed cancer cells to grow. •Vitamin D deficiency is widespread because people spend less time in the sun and, when they do, they wear sunscreen, which prevents the rays of the sun from generating vitamin D in the skin.

Drug Controversy: Medicare & Chemotherapy Drugs

•In 2013, cancer clinics across the United States began refusing to give chemotherapy drugs to Medicare patients when federal budget cuts led to a reduction in Medicare payments. •One clinic stopped seeing one-third of their Medicare patients and stopped administering the most expensive chemotherapy drugs to the rest of their Medicare patients in order to continue to keep the clinic open and financially sound.

Historical Notes: doxorubicin

•In the 1950s, Italian researchers extracted the drug doxorubicin from a fungus-like bacterium found in the soil near an ancient castle in Italy. •This bacterium produces a bright red pigment. •French researchers discovered it at the same time. •Together, both groups decided on a name for the drug: daunorubicin, which was taken from Dauni (an ancient people that lived in that region of Italy) and rubis (the French word for ruby) •Italian researchers then modified the drug, named the new generic drug doxorubicin, and assigned the trade name Adriamycin (named for the Adriatic Sea off the coast of Italy).

Historical Notes: nitrogen mustard

•In the early 1900s, the only treatments available for cancer were surgical excision and radiation therapy. •The discovery of the first chemotherapy drug, nitrogen mustard, came about serendipitously (discovered by chance) •During the 1940s, researchers who were reviewing medical records from World War I noticed that Allied soldiers who were exposed to the chemical weapon nitrogen mustard gas had a decreased level of WBCs. •It was thought that this adverse effect could be used as a therapeutic effect in patients with leukemia whose WBC counts were abnormally elevated. •Nitrogen mustard (the drug mechlorethamine) and its derivative drugs are still used to treat leukemia today.

Did You Know? BCG & human tuberculosis

•In third-world countries where human tuberculosis is common, BCG is given as a vaccine to stimulate the body to make antibodies against the similar human tuberculosis bacterium (Mycobacterium tuberculosis).

Chemotherapy Protocols

•Introduced in the late 1960s §Combine the effectiveness of several chemotherapy drugs and direct them against one specific type of cancer §Prior to this, only single-agent chemotherapy drugs were used. •Selecting drugs §The success of each drug in treating that type of cancer is compared with that of other drugs. §Most successful drugs are combined into one protocol. •Different therapeutic effects of the various chemotherapy drugs §Maximize the effectiveness of therapy §Minimize the side effects that would be caused by a large dose of just one drug •Today, chemotherapy protocols are used to treat nearly every type of cancer. •Designated by acronyms that combine the first letters of the generic name drug or trade name drug or an abbreviation of that drug name in the protocol •MACC §Methotrexate §Adriamycin (doxorubicin) §Cyclophosphamide (Cytoxan) §CeeNU (lomustine)

Did You Know? Leucovorin

•Leucovorin is a derivative of the B vitamin folic acid. •Administration of leucovorin after methotrexate chemotherapy is known as leucovorin rescue because the drug rescues the patient from the toxic effects of methotrexate. •Leucovorin is also known as citrovorum factor and folinic acid.

Immunomodulator Chemotherapy Drugs

•Modulate and regulate the immune system •Active against cancer cells •Inhibit inflammation •Inhibit the formation of new blood vessels •Interferon chemotherapy drugs treat viral diseases, such as hepatitis. --Interferon alfa-2b (Intron A) --Peginterferon alfa-2b (Sylatron) •Interleukin is a chemical that stimulates lymphocytes to attack viruses and also activates natural killer (NK) cells that attack cancer cells. --Aldesleukin (Proleukin) •These drugs are only used to treat multiple myeloma. §Lenalidomide (Revlimid) §Pomalidomide (Pomalyst) §Thalidomide (Thalomid)

Chemotherapy Antibiotic Drugs

•Not interchangeable with regular antibiotic drugs •Human cells §Have a cell membrane (not a cell wall) §Not affected by antibiotic drugs that treat bacterial infections §Affected by chemotherapy antibiotic drugs •Inhibit the production of: §DNA §RNA §Some cellular proteins •Some of these drugs block the enzyme that normally splits each DNA strand into two strands prior to cell division. •Used to treat different types of cancer Drug list: •Bleomycin •Dactinomycin (Cosmegen) •Daunorubicin (Cerubidine) •Doxorubicin (Adriamycin) •Epirubicin (Ellence) •Idarubicin (Idamycin) •Mitomycin •Valrubicin (Valstar)

Did You Know? Platinum

•Platinum is a precious metal that is mostly mined in South Africa. •It takes 10 tons of ore to produce 1 ounce of platinum. •Cisplatin was the first of the platinum chemotherapy drugs. •It was discovered when a researcher at Michigan State University was studying whether bacteria could multiply in an electrical field. •He placed platinum electrodes that would conduct electricity into a solution of bacteria. •When the electrical field was turned on, the bacteria did not multiply, but they also did not multiply when the electrical field was turned off. •He found that it was the platinum in the electrodes that was toxic to the bacteria. •This ability to stop a cell from dividing was later applied to the treatment of cancer. •The generic drug name cisplatin was approved by the FDA in 1978. •The drug was originally known as cis-platinum because it was in the cis isomer form of the platinum molecule.

Drug Alert: generic and trade name drugs

•Some chemotherapy drugs have older drug names that were used during clinical trials before the generic and trade name drugs were marketed. •Such is the case for doxorubicin (which was formerly known as daunorubicin) dactinomycin (which was formerly known as actinomycin D), cisplatin (which was formerly known as cis-platinum), and for many other chemotherapy drugs.

Retinoid and Rexinoid Chemotherapy Drugs

•Structurally related to vitamin A (retinoic acid) •Normally, vitamin A (particularly in the skin) regulates cell differentiation and growth. •Bind to vitamin A receptors on cancer cells, and help them become more normal in their cell differentiation and growth •Alitretinoin (Panretin) --Used topically to treat the cancerous skin lesions of T-cell lymphoma and Kaposi sarcoma •Bexarotene (Targretin) --Used to treat the cancerous skin lesions of T-cell lymphoma •Tretinoin (Vesanoid) --Used to treat leukemia

Did You Know? taxane chemotherapy drugs

•The taxane chemotherapy drugs are so named because they were originally derived from an extract of the bark of the Pacific yew tree whose scientific name is Taxus brevifolia. •Paclitaxel was the first of the taxane chemotherapy drugs. •This yew tree, which only grows in the Pacific Northwest, is small and grows slowly, and collection of the bark kills the tree. •Now, the needles of European and Himalayan yews are used because they contain 10 times more paclitaxel and harvesting of the needles does not kill the trees.

In Depth: Cancer

•To properly treat any type of cancer, the physician must determine two things: §Type of cancer •Biopsy is taken from the tumor site. •Blood specimen is drawn to examine the blood cells. §Stage of cancer •The extent of cancer progression •Indicates whether or not the cancer has spread •Secondary sites, such as: -Regional lymph nodes -Other parts of the body •The selection of appropriate chemotherapy drugs is based on the type and stage of the cancer. •A treatment that is appropriate for one type of cancer is usually not appropriate for a different type of cancer. §It may not even be appropriate for the same cancer that has progressed to a more advanced stage.