Anti Cancer Drugs Lecture PDF Flashcards
Administration of cytotoxic drugs
Prolonged infusion or in multiple doses over an extended period of time, require special handling as can be very toxic to handle with direct contact
Alkylating agents mech of action
Transfer alkyl group to DNA molecule, tie up DNA molecule eliminating ability of DNA to untwist and allow replication of genetic code or vital protein production, can occur during any stage of the cell cycle (cell cycle nonspecific)
Cyclophosphamide (cytoxan, neosar) drug class and function
Nitrogen mustard alkylating agent most commonly used for different types of leukemia
Chlorambucil (leukaran) drug class and function
Nitrogen mustard alkylating agent that is the safest to use for cancer treatment
Major dose limiting toxicity in the nitrosureas chemo agent drug class
Delayed bone marrow suppression
Carmustine (BCNU, glaidel) drug classand function
Nitrosureas alkylating agent, used to easily penetrate BBB and act on metastatic tumors of brain, can be administered by biodegradable wafer implanted into cavity when tumor is removed
Cisplatin (platinol) drug class and function and ADR’s (3)
Platinum compound (forms cross links with DNA similar to alkylating agents),used to treat metastatic testicular and ovarian cancers or advanced bladder cancer but has many adverse effects including nephrotoxicity, neurotoxicity, and GI distress
Antimetabolites mech of action
Structurally similar to endogenous metabolites to compete with compounds during DNA/RNA biosynthesis forming nonfunctional gene product making it particularly toxic to cells with large growth fraction and acts during the S phase
3 classes of antimetabolites and example of each
Folic acid analogues - methotrexate
Pyrimidine analogues - cytarabine, 5-FU
Purine analogues - mercaptopurine
2 ways to get methotrexate to be taken up by the cancer cells
- massive dosing forces drug into cell
- leucovorin
Methotrexate indications (3)
- choriocarcinoma
- ALL
- skin disorders
Cytarabine indications (1)
-AML in 7+3 regimen
5-FU indications (2) and ADR’s (2)
- solid tumors
- topical premalignant keratosis
-Bone marrow suppression, hyperpigmentation
Hypomethylating agents mech of action
Induce apoptosis and restore normal frunction to genes involved with cell differentiation and proliferation
Antineoplastic antibiotics function and 2 subcategories
Classified as antibiotics but reserved for neoplastic disease because of high toxicity
-anthracyclines and nonanthracyclines
Doxorubicin drug class, primary indication (1), ADR (1)
Anthracycline antineoplastic antibiotics
- lymphomas
- cardiotoxicity related to total cumulative dose
Liposomal (doxil)/daunorubicin
Reformulations similar to doxorubicin with different function, daunorubicin used only for AIDS related kaposi’s sarcoma
Bleomycin (blenoxane) drug class, ADR (1)
Nonanthracycline antineoplastic antibiotic
-pulmonary toxicity dose limiting toxicity
Vinca alkaloids mech of action
Work during M phase to bind to microtubules and initiate destruction and dissolution of the microtubules
Mitotic inhibitors sub divisions
vinca alkaloids and taxanes
Vincristine vs vinblastine drug class and differences
Both vinca alkaloid mitotic inhibitors vincristine is toxic to peripheral nerves but does little damage to bone marrow, vise versa for vinblastine
Paclitaxel (abraxane) drug class and ADR (1)
Taxane mitotic inhibitor
-severe hypersensitivity
Topoisomerase inhibitors mech of action
Block enzymes that cut apart DNA strand
Topotecan (hycamtin) drug class function
Topoisomerase inhibitor
Asparaginase (elspar) mech of action
Some tumor cells especially leukemic require extracellular supply of aspargine and these break it down in the blood stream depriving tumors
Presence of TILs
Tumor infiltrating lymphocytes that indicate the immune system is responding to a tumor and is associated with better outcome
Immune checkpoint proteins
Surface proteins on the surface of T cells that recognize specific partner proteins on other cells sending an off signal not to attack those cells, expressed in high levels of some tumor cells to avoid immune destruction
Check point inhibitor drug mech of action
Blocks interaction between T cell and cancer cell at the check point to allow the T cell to target and kill the cancer cell - a potentiator of the T cell response
Pembolizumab (keytruda) and nivolumab (opdivo) drug class
Check point inhibitor drugs
CAR-T cell therapy and one big ADR
Genetically modifying patient’s T cell in lab to express protein known as chimeric antigen receptor to attach to receptor on surface of cancer cells improving ability to attack (requires chemo and whole body radiation to remove current immune cells that can impede activty of the incoming modified T cells)
-cytokine release syndrome
Tumor infiltrating lymphocyte therapy and one big ADR
Growth in lab T cells naturally found against tumor before reinfusion to kill tumor before it becomes immunoresistant
-capillary leak syndrome
Antibody drug conjugates and example
Linking of an antibody to a toxic substance for use in treatment of cancer, adotrastuzumab emantasine
Sipuleucel T (provenge)
cancer treatment vaccine designed to stimulate the immune attack against prostate cancer cells in asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer
Thalidomide drug class and function
Immunomodulatory drug that helps inhibit angiogenesis
Common side effects of biological cancer therapies (3)
- soreness or itching
- flu like symptoms
- long term autoimmune disorders
Hormonal agents taken for years to reduce recurrence of breast cancer or in high risk patients as a prevantitve measure or to treat estrogen receptor tumors (2)
Antiestrogens such as tamoxifen, aromatase inhibitors such as anastrazole
Raloxifene (evista) key differences from tamoxifen
Does NOT increase risk of endometrial cancer
Most widely used therapy for prostate cancer treatment
Androgen deprivation therapy
Why is drug therapy better than castration at reducing androgen levels?
It acts at both the testes and the adrenals (produce up to 10% of the androgens)
Leuprolide (eligard) drug class and function, ADR’s (3)
Synthetic analogue agonist of GnRH indicated in advanced carcinoma of the prostate to offer palliative care and as an alternative to orchiectomy or estrogen therapy by suppressing testosterone production long term thru desensitizing the GnRH receptors which then cause a drop in LH release and testosterone production
-hot flashes, impotence and loss of libido, and elevation of testosterone early in treatment
Degarelix (firmagon) drug class and function
GnRH antagonist, often used for palliative therapy of advanced prostate cancer as alternative agonists
Flutamide (eulexin) drug class, function
Androgen receptor blocker, used alongside a GnRH agonist indicated only for metastatic prostate cancer to prevent tumor flaring caused by the GnRH agonist
