Anticancer Drugs

Anticancer Drugs
• In the US, cancer is the 2nd cause of death (heart dx - 1st)
• Results from the alterations in DNA w/in the cell
• Use of anticancer drugs include - cure, control, palliative
• Chemo may be used as sole Rx of Ca or in conjunction w/
radiation & surgery
• Cell-Cycle Nonspecific & Specific - Anticancer drugs cause
Ca cell death by interfering w/ Ca cell replication
- Interferes w/ either all phases or a specific phase of the
cell cycle (pg. 575, fig. VII-I)
 Anticancer Drugs
- Cell-cycle nonspecific (CCNS) = act on any phase during
the cell cycle
- kill the cell during the dividing & resting phase of cell
cycle: alkylating drugs, antitumor antibiotics, hormones
- Cell-cycle specific (CCS) = act on a specific phase of the
cell cycle
- effective against rapidly growing Ca cells:
antimetabolites, vica alkaloids, antitumor antibiotics
• Growth fraction & doubling time are two factors that play
a major role in the Ca cell response to the anticancer drug
 Anticancer Drugs
- Anticancer drugs are more effective against the Ca cells
having a high growth fraction - leukemias & some
lymphomas
- Ca of the breast & colon & melanomas = low growth
fraction = poor response to antineoplastics
- small & early forming Ca cells & fast-growing tumors
respond well to anticancer drugs
• Drug Rx for early dx = higher cure rate than late stages
• Solid tumors = low growth fraction = less sensitive to
drugs
 Anticancer Drugs
• Higher doses of drugs result in better tumoricidal (killing)
effects
• Ca growth usually faster in earlier stages. As tumor grows
bld supply dec & growth rate dec. = drugs more effective
against sm. tumors w/ sufficient bld supply
• Cancer Chemotherapy - tumor cells are similar to normal
cells in that it is difficult for antiCa drugs to be selective in
killing tumor cells & not normal cells
- Drug protocol = therapy too long & doses too high = toxic
- Eliminating every Ca cell = difficult (1 mill. cells could
remain w/o symptoms - ??? on continuing Ca therapy
 Anticancer Drugs
• Drug Resistance - tumor resistance can develop against an
antiCa drug d/t drug used infrequently or the tumor’s
location limits the effectiveness
- Brain tumors respond poorly (BBB)
• Combination Chemotherapy - Single-agent drug therapy
seldom used
- Combo of drugs to enhance tumoricidal effects
- CCS & CCNS are often combined to max. cell deaths
- dec. drug resistance, shorten & intensify drug effect
- inc. destruction of Ca cells, dec. drug toxicity - several
drugs = lower doses = less injury to normal cells
 Anticancer Drugs
• Alkylating Drugs - one of the largest groups of Ca
drugs
- Kill cells by forming cross-links on DNA strands
- Belong to the CCNS category & affect all phases of
the cell cycle - effective against many types of
cancers: acute & chronic leukemias, lymphomas,
mult. myeloma, solid tumors (breast, ovaries, uterus,
lungs)
- Classified into 4 groups: Nitrogen mustards
(Cyclophosphamide), nitrosoureas (Carmustine), alkyl
sulfonates (Busulfan), alkylating-like drugs (Cisplatin)
 Anticancer Drugs
• Cyclophosphamide (Cytoxan) - Nitrogen mustard
- Action - Inhibition of protein synthesis through
interference w/ DNA replication by alkylation of DNA
- Use - Hodgkin’s dx, solid tumors
- SE - bone marrow suppression , alopecia, N & V,
diarrhea, wt. loss, hematuria (maintain adequate
hydration), impotence, sterility
- An early antiCa drugs, can be administered PO
 Anticancer Drugs
• Antimetabolites - Oldest group
- Resemble natural metabolites - disrupt the metabolic
processes & some of the agents inhibit enzyme
synthesis
- CCS (5-FU, floxuridine - also CCNS)
- Subdivided into folic acid (folate) antagonists
(Methotrexate) - also used as an immunosuppressant
following organ transplant - substitutes for folic acid,
needed for the synthesis of proteins & DNA;
pyrimidine analogues (5-fluorouracil); purine
analogues (6-mercaptopurine)
 Anticancer Drugs
• Flurouracil (Adrucil, 5-FU, Efudex) - IV
- Action - CCS, blocks the enzyme action necessary for
DNA & RNA synthesis
- low therapeutic index
- alone or w/ other drugs, can cross BBB
- Use - Ca of breast, cervix, colon, ovary, stomach,
pancreas
- SE - N, V, diarrhea, alopecia, rash, bone marrow
suppression, stomatitis (inflammation of oral
mucosa)
 Anticancer Drugs
• Antitumor Antibiotics - (Bleomycin, dactinomycin,
daunorubicin, doxorubicin) - inhibit protein & RNA
synthesis & bind DNA causing fragmentation
- Classified as CCNS (except for bleomycin)
- Drugs differ from each other & are used for diff. Ca’s
• Doxorubicin (Adriamycin) - IV
- Action - Inhibits DNA & RNA synthesis
- Use - W/ other agents for Ca of breast, ovaries, lung,
bladder, leukemias, lymphomas
- SE - Similar to general adverse rxns to antineoplastics
 Anticancer Drugs
- Capable of causing vesication - blistering of tissue if
drug leaks out into surrounding interstitial tissue -
rxn ranges from painful, reddened swelling to deep
necrotic lesion needing debridement & skin grafts
- Drug is a deep red color - urine will be red 1 - 2 days
after administration
- Can cause cardiotoxicity
• Mitotic Inhibitors (Vinca Alkaloids) - block cell
division at M phase of cell cycle (Vincristine,
Vinblastine, Vinorelbine tartrate) - CCS
 Anticancer Drugs
- Single drugs or in combo therapy
- SE - leukopenia, alopecia, stomatitis, N,V, neurotoxicity
• Hormones & Hormone Antagonisits - Used in combo
therapy for Rx of various Ca.
- 2 major actions: 1) Agonists that inhibit tumor cell growth
- estrogen, progestins, androgens, adrenocorticosteroids
& 2) Antagonists that compete w/ endogenous hormone -
aminoglutethimide, tamoxifen
• Corticosteroids (glucocorticoids) classified as
antiinflammatory agents - suppressing the inflammatory
process that occurs w/ tissue involvement
 Anticancer Drugs
- Hormones also suppress leukicytes & is effective in
controlling leukemia & lymphoma
- Used w/ other drugs as part of an antineoplastic
regimen - MOPP (oncovin, procarbazine &
prednisone) - Hodgkin’s disease
- Prednisone frequently prescribed - inexpensive
cortisone derivative
- Dexamethasone & hydrocortisone - IM or IV - can
decrease cerebral edema caused by a brain tumor
 Anticancer Drugs
• Tamoxifen (Nolvadex) -
- Action - exact neoplastic action unknown, acts as an
estrogen antagonist
- Use - Breast cancer in women and men
- SE - Adverse rxn’s usually minor & well tolerated
• Miscellaneous Agents - antineoplastic drugs whose
MOA does not place them in a category. Used in
combo w/ other Ca drugs to Rx a variety of solid
tumors & hematologic malignancies - pactitaxel
(Taxol), docetaxel (Taxotere), pentostatin (Nipent),
etoposide (VP-16)