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96 Cards in this Set
- Front
- Back
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Cancer Biology/Cell Kinetics
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Similar to bacterial kinetics
Doubling time = 1 g to 2 g Generation time = 1 cell to 2 cells (controls growth rate) Growth is exponential |
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Cell Cycle
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G1 = protein and RNA synthesis
S = DNA synthesis G2 = protein and RNA synthesis M = mitosis/cell division G0 = non-dividing |
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Total Kill Concept
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One L1210 Leukemia cell is FATAL to a mouse
- a given dose will kill a constant percentage of cells per unit time - # of original cells before therapy will determine # of cells surviving therapy |
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Combination Chemotherapy
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ABVD
BACOP CHOP CMF CVP MOPP POMP |
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Carmustine-Cimetidine
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Additive bone marrow depression
Cimetidine inhibits Carmustine metabolism |
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Cyclophosphamide-Allopurinol
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Bone marrow depression
Allopurinal alters the liver metabolism of cyclophosphamide |
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Mercaptopurine - Allopurinol
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Increased mercaptopurine toxicity
Allopurinol inhibits xanthine oxidase which is involved in mercaptopurine metabolism |
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Methotrexate - Ethyl Alcohol
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Hepatotoxicity
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Methotrexate-Aspirin
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Increased serum concentration of free MTX
Aspirin displaces MTX from plasma proteins and competes for its elimination |
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MTX-Cytarabine
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Syngeristic effects
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MTX-Neomycin
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Decreased MTX absorption
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MTX-Probenecid
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Increased MTX in serum
Probenecid inhibits MTX excretion |
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MTX-Sodium Bicarb
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Increased renal elimination of MTX due to alkalinization of urine
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MTX-Sulfisoxazole
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Decreased plasma binding and renal clearance of MTX
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Antineoplastic Agents
General Toxicities |
-pancytopenia
-thinning and denudation of mucosa -hair loss, skin lesions -teratogenic, sterility -immunosuppression -cancer -gout |
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Alkylating Agents MOA
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alkylate nucleic acids and proteins
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Alkylating Agents Kinetics
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quickly metabolized, distributed, excreted
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Alkylating Agents Toxicities
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Nausea, vomiting
Alopecia Thrombocytopenia Hemorrhagic cystitis Increased skin pigmentation |
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Alkylating Agents Resistance
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Decreased take up of drug
Increased ability to excise cross-linked residues and repair the defect |
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Mechlorethamine Uses
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Hodgkin's
Lymphosarcoma Wilm's Tumor |
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Chlorambucil Uses
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Lymphosarcoma
CLL Ovarian CA Hodgkin's |
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Cyclophosphamide Uses
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ALL
Neuroblastoma Myeloma Wilm's tumor |
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Melphalan uses
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Multiple myeloma
Melanoma |
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ThioTEPA uses
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Ovarian CA
Lymphosarcoma |
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Busulfan Uses
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CML
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Uracial Mustard Uses
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CLL
Lymphoma Hodgkin's |
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Pipobroman Uses
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Polycythemia vera
Chronic granulocytic leukemias |
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BCNU Uses
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Astrocytoma (CNS tumors)
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Procarbazine Uses
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Hodgkin's
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Dacarbazine Uses
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Hodgkin's
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Altretamine Uses
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Ovarian CA
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cis-DDP MOA
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Alkylates DNA, forms coordination complexes
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cis-DDP Toxicity
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Kidney damage
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cis-DDP uses
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Testicular CA
Ovarian CA Bladder CA Head and neck CA |
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Carboplatin
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Similar to cis-DDP
Less toxic |
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6-Mercaptopurine
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Purine analogue/anti-metabolite
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6-Mercaptopurine MOA
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Suppression of de novo purine biosyntheis (due to psuedo-feedback inhibition)
Inhibition of adenylate and guanylate formation Inhibition of interconversion reactions in purine metabolism |
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6-Mercaptopurine Kinetics
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Oral
Complete GI absorption 90% protein bound t1/2 = 90 minutes |
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6-Mercaptopurine Toxicities
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Leukopenia, thrombocytopenia, anemia
Anorexia Jaundice |
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6-Mercaptopurine Uses
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Antileukemic
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Azathioprine
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Less toxic than 6-MP
Prevents transplant rejection Used in RA and SLE |
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Pyrimidine Analogues
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5-FU
ARA-C |
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5-FU MOA
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Blocks thymidylate/DNA synthesis
Depresses RNA synthesis |
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5-FU Kinetics
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IV
Excreted as expired CO2 after 24 hours |
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5-FU Toxicities
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Leukopenia, thrombocytopenia
Anorexia, diarrhea, stomatitis |
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5-FU USes
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GI neoplams
Female genital tract CA Breast CA |
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ARA-C MOA
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Inhibits DNA synthesis
Incorporated into internucleotide linkages |
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ARA-C Kinetics
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IV
Cleared in 15-30 minutes Metabolism inactivates |
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ARA-C Toxicities
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Leukopenia, thrombocytopenia, anemia
Anorexia, nausea, vomiting |
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ARA-C Uses
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Acute granulocytic leukemias
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Folic Acid Analogues (MTX)Kinetics
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Absorbed well
Peak levels in 1 hour 50% protein bound 24 hour, complete excretion |
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MTX Toxicities
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Anorexia, weight loss, bloody diarrhea
Leukopenia Depression, coma Severe hemorrhagic enteritis Dermatitis, GI ulceration, infection, bleeding |
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MTX Uses
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Choriocarcinoma
ALL Psoriasis |
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Vinca Alkaloids (Vinblastine/Vincristine)MOA
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Bind microtubular proteins
Prevent spindle formation Inhibit cell cycle |
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Vinca Alkaloids (Vinblastine/Vincristine) Toxicities
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Bone marrow depression
Pancytopenia Neurological Problems |
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Vinca Alkaloids (Vinblastine/Vincristine) Uses
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Solid tumors
Lymphosarcoma Hodgkin's Lymphoma Choriocarcinoma Acute leukemias |
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Epipodophyllotoxins
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Etoposide
Teniposide |
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Epipodophyllotoxins MOA
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Block S-G2 phase of cell cyle
Affect topoisomerase II |
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Epipodophyllotoxins Toxicities
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Leukopenia, thrombocytopenia
Nausea, vomiting, stomatitis, diarrhea Alopecia Hepatic toxicity |
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Epipodophyllotoxins USes
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Testicular tumors
NHL AML Breast CA Kaposi's sarcoma ALL |
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Taxol MOA
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Binds tubulin dimers
Disrupts mitosis |
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Taxol Toxicities
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Myelosuppression
Alopecia Peripheral neuropathies Muscle and joint pain CV problems Hypersensitivity |
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Taxol Uses
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Breast CA
Ovarian CA Lung CA Head and neck CA |
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Daunorubicin/Adriamycin MOA
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Intercalate DNA
Prevent replication Inhibit topoisomerase II |
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Daunorubicin/Adriamycin Kinetics
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t1/2 = 45 minutes
Bile excretion |
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Daunorubicin Toxicities
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Bone marrow depression
Tachycardia, arrhythmias Cardiorespiratory symptoms |
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Adriamycin Toxicities
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Bone marrow depression
CHF Nausea |
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Daunorubicin Uses
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Acute leukemias
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Adriamycin Uses
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Lung CA
Breast CA Bladder CA Lymphoma Sarcomas |
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Plicamycin MOA
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Binds DNA
inhibits RNA synthesis Requires guanine |
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Plicamycin Uses
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Embryonal cell testicular tumors
Paget's, hypercalcemia |
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Dactinomycin MOA
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Prevents DNA synthesis by binding DNA
Guanine and helical configuration required |
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Dactinomycin Kinetics
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IV
Bile and urine excretion |
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Dactinomycin Toxicities
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Hematopoietic depression, leukopenia, anemia, pancytopenia
Nausea, vomiting, stomatitis Erythema, acne, alopecia Fatigue, fever, myalgia |
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Dactinomycin Uses
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Wilm's Tumor
Rhabdomyosarcoma Ewing's sarcoma Osteogenic sarcoma Choriocarcinoma Uterine and testicular CA |
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Bleomycin MOA
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Inhibit DNA synthesis
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Bleomycin Toxicities
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Pulmonary fibrosis
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Bleomycin Uses
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Squamous cell carcinoma of skin
Testicular tumor Lymphoma |
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Mitomycin MOA
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Alkylating agent
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Mitomycin Toxicities
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Myelosuppression
Renal toxicity |
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Mitomycin Uses
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Gastric adenocarcinoma
Tumors of cervix, colon, rectum, pancreas, breast, bladder, lung |
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Prednisone MOA
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Inhibit RNA and protein synthesis
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Prednisone Toxicities
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Fluid disturbances
Hyperglycemia, glycosuria Peptic ulceration Infection Psychiatric disturbances Skeletal atrophy |
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Predinose Uses
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ALL
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Other Hormone Therapies
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Progesterone (endometrial CA)
Diethylbestrol Flutamide (antiandrogen) Estramustine (estrogen + alkylating agent) Leuprolide (GnRH analog) Testosterone proprionate Antiestrogens Aminoglutethimide |
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Estrogen/Androgen MOA
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Change hormonal environment of tumor
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Estrogen/Androgen Uses
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Prostatic CA
Mammary CA |
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Monoclonal Antibody (Herceptin) MOA
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Inhibits tumor cell growth by binding to HER2
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Monoclonal Antibody (Herceptin) Toxicities
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Weakening of heart muscles leading to CHF
Leukopenia, anemia Diarrhea, abdominal pain Chills, fever, pain, weakness, anusea, vomiting, headache |
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Monoclonal Antibody (Herceptin) Uses
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Advanced breast CA
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Hydroxyurea MOA
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inhibits ribonucleoside diphosphate reductase
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Hydroxyurea Uses
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Chronic granulocytic leukemia
Polycythemia vera Solid tumors |
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Mitotane Uses
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Adrenocortical CA (Palliative tx)
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L-asparaginase Uses
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ALL
(SE: nausea, liver dysfunction, hypersensitivity) |
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Gold-198 Uses
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Pleural effusions and ascites secondary to cancer
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Sodium Phosphate P 32 Uses
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Polycythemia Vera
CML |
