10 Anti-neoplastic Drugs Flashcards
Chemotherapy given to induce a remission
Induction chemotherapy
Disappearance of s/s of cancer
Remission
Reappearance of s/s
Relapse
Course of tx wherein drugs are given for a specific number of days followed by a rest period
Cycle
Chemotherapy given after the primary therapy
Usually in advanced cancers, to decrease recurrence and improve survival
Adjuvant chemotherapy
Chemotherapy given before the primary therapy
Usually to reduce tumor mass
Neoadjuvant chemotherapy
Two kinds of drugs depending on the cell cycle
Cell cycle-specific
Cell cycle-nonspecific
Kills cells in the cell cycle, sometimes they are phase-specific
Antimetabolites, bleomycin, plant alkaloids, hormones
Toxicity proportional to length of exposure, schedule dependent
Effective vs tumors with high growth fraction
Cell cycle-specific
Can kill those in cell cycle and in those in G0, dose-dependent,
Alkylating agents and antitumor antibiotics except bleomycin
Toxicity is dose dependent
Effective in low and high growth fraction tumors
Cell cycle-nonspecific
Growth at every instant is exponential but with a growth constant that is simultaneously exponentially slowing due to depletion of nutrients
Advanced cancers are less responsive to chemotherapy
Curability is inversely proportional to cell number
Gompertzian Growth
A constant fraction of cells is killed by a given drug dose
Log-kill hypothesis
Factors that affect cell-kill
Dose intensity Schedule Drug resistance Tumor site Px performance status
Drug selection
Single drug (choriocarcinoma, Burkitt's lymphoma) Combination chemotherapy
Anti-cancer regimen for lung Ca
Etoposide
Cisplastin
Vincristine
Anti-cancer regimen for breast Ca
Cyclophosphamide
Methotrexate
Fluorouracil
General toxicities of anti-cancer regimen
Myelosuppression
Nausea and vomiting
Cytotoxicity to other cells
Usual dose-limiting toxicity, prevents you from giving a drug at a dose and schedule you want
Myelosuppression
Exceptions for myelosuppression
Hormones Vincristine Bleomycin Asparaginase Cisplastin Streptozocin
Most common toxicity and CNS in origin
Especially cisplastin
Nausea and vomiting
Tx for nausea and vomiting
Ondansetron and granisetron (serotonin antagonists)
To manage the myelosuppression among cancer patients due to chemotherapy, give them:
Granulocyte colony stimulating factor (G-CSF) + filgastrim
Granulocyte-macrophage colony stimulating factor (GM-CSF) + molgramostim
Mechanisms of acquired drug resistance
Improved proficiency in DNA repair Decrease in drug activation Increase in drug inactivation Decrease in cellular uptake of drug Increase in efflux of drug due to increase in p-glycoprotein
Traditional chemotherapy
Antimetabolites
Alkylating agents
Antibiotics
Natural products
Specific chemotherapy
Hormones
Biological treatment
Targeted therapy
Examples of antimetabolites
Folic acid analogs
Purine analogs
Pyrimidine analogs
Examples of alkylating agents
Nitrogen mustard/bischloroethyl amines
Alkyl sulfonates
Nitrosureas
Platinum analogs
Examples of antibiotics
Dactinomycin
Anthracyclines
Examples of natural products
Vinca alkaloids
Podophyllotoxins
Taxanes
Camptothecins
Folic acid analogs are activated intracellularly by ______ forming polyglutamate metabolites
folylpolyglutamate synthase
Folic acid analog drugs
Methotrexate
Pemetrexed
Prelatrexate
Actions of folic acid analogs
Inhibits thymidylate synthesis, de novo purine synthesis, amino acid (serine, methionine) synthesis
Competes with folic acid for sites in dihydrofolate reductase, thus inhibiting DNA, RNA, protein synthesis
Methotrexate
Source of reduced folates
Prevents/treats toxic effects of folic acid analogs
Leucovorin (folinic acid)
Pharmacokinetics of MTX
Well absorbed orally, metabolized in liver, excreted in urine (kidney-route of elimination)
Adverse effects of MTX
Myelosuppression
Stomatitis
Diarrhea - hepatotoxicity
Uses of MTX
ALL ChorioCa NHL Psoriasis Immunosuppression RA
Purine analog
Mercaptopurine (6-MP)
Mercaptopurine is converted to nucleotide form by _____, then incorporated into DNA replacing ____, thus inhibiting de novo purine synthesis
HGPRT
Guanine
Mercaptopurine is oxidized in liver by _____
Xanthine oxidase
Decrease the dose of mercaptopurine if given with _____ among gout patients
Xanthine oxidase inhibitor
Allopurinol
Adverse effects of mercaptopurine
Bone marrow depression
Hepatotoxicity
Uses of mercaptopurine
Leukemia: ALL, AML, CML
Pyrimidine analogs
Fluorouracil (5-FU)
Cytarabine/cytosine arabinoside
The metabolite of 5-FU, ______, binds with ______
FdUMP
Thymidylate synthetase
Use of 5-FU
IV for adenoCa (colorectal)
Adverse effects of 5-FU
Myelosuppression, mucositis, diarrhea, hand-foot syndrome (capecitabine)
Metabolite of cytarabine that blocks DNA synthesis and incorporated into the DNA and RNA
ara-CTP
Use of cytarabine
Hematologic malignancies (AML) Not solid tumors