Principles of Chemotherapy Flashcards
What are the possible approaches to the management of cancer?
Surgery
Radiation
Chemotherapy
What does the approach to management depend on?
The type of cancer
What is neoadjuvant chemotherapy?
Chemotherapy that is given before the surgery to shrink tumour
What is adjuvant chemotherapy?
Chemotherapy that is given to treat or prevent micro-metastases after the surgery and radiation treatment
What is maintenance chemotherapy?
Chemotherapy that is given at lower doses to prolong remission/prevent recurrence of tumour
What is palliative chemotherapy?
Chemotherapy that is given when neoplasms are disseminated and not amenable for surgery
What are the characteristics of cancer cells?
Uncontrolled proliferation
Immortalisation
Loss of function
Invasiveness & Metastasis
Neovascularization
what is Gompertzian Kinetics?
Slow linear growth at smallest and largest tumor sizer
Exponential growth in between
What is the “Log Kill” Hypothesis?
Drugs are given at a specific dose kills the same fraction of cancer cells every time, independent of the total number of cancer cells
Why is the “Log Kill” Chemotherapy treatment given in repeated doses?
Only a fraction of the cells die with each dose so there has to be repetition in order to continue on reducing the size of the tumour.
What controls/limits the chemotherapy cycle of the “Log Kill” chemotherapy?
The toxicity to the patient
What is the one thing that you cannot prevent with the “Log Kill” chemotherapy?
There will be a fraction of cells that will “rebirth” in between cycles
What does the fraction of cell killed vary on?
The cell growth rate
What is the solution for the “disadvantages” of the “Log Kill” chemotherapy?
Combination therapy and repeated cycles of treatment
Why is combination therapy more effective than monotehrapy?
Different drugs may be effective against a particular tumour via different mechanisms
What is the method used in order to avoid cumulative adverse effects?
Drugs of different toxicities can be used
What is another “advantage” of combination therapy?
The use of different drugs decreases the risk of resistance to the chemotherapy regimen
What are the problems of anticancer chemotherapy?
Lack of highly selective toxic agents
There are once a few selective drug targets
Adverse effects
Resistance
What are the adverse effects of anti-neoplastic drugs?
They affect and destroy rapidly dividing normal cells
Very narrow therapeutic index, serious side effects observed during therapeutic index as well
What are examples of normal rapidly dividing cells targeted by anti-neoplastic drugs?
Bone marrow
Gut epithelium
Spermatogenic cells
Lymphoid tissue
Hair follicles
Fetus
What are the most common side effects of antineoplatics?
Severe GI disturbances
Severe stomatitis
Alopecia
Toxicities such as myelosuppression & immunosuppression
Some toxicities are specific to:
Certain drugs
What are the specific side effects of Cisplatin?
Ototoxicity
Nephrotoxicity
Nausea/Vomiting
Which drug has the specific side effect of cardiotoxicity?
Doxorubicin/Daunorubicin
What is the specific side effect of Bleomycin/Busulfan?
Pulmonary toxicity
Which drug has specific side effect of hemorrhagic cystitis?
Cyclophosphamide/Ifosfamide
Which drugs have the common side effect of peripheral neuropathy?
Oxaliplatin
Vincristine
Taxanes
What is the specific side effect of Irinotecan?
Diarrhea
What are the different kinds of resistance that may develop?
Innate or Acquired
What is innate resistance?
Most of the cells in the tumour are resistant to initial treatment
What is acquired resistance?
Initial treatment kills the cells in the tumour and the later cells become resistant to the next cycles
What are the two categories of antineoplastic drugs?
Cell-cyle phase independent drugs
Cell-cycle dependent drugs
Which kind of antineoplastic drugs have the concentration dependent effect?
Cell-cycle phase independent drugs: as dose increases so does cell kill
What are examples of non-cell cycle specific drugs?
Alkylating gents
Antitumor antibiotics
Nitrosoureas
What are examples of M phase inhibitors?
Vinblastine
Vincristine
Paclitaxel
What are examples of S-phase specific drugs?
Cytarabine
Mercaptopurine
Thioguanine
Fluorouracil
Methotrexate
Hydroxyurea
Irinotecan
Etoposide
How are the growth promoting hormones stopped?
Anti-hormones
How is the tumor blood supply inhibited?
Angiogenesis inhibitors
How is DNA synthesis inhibited?
Antimetabolites
How is DNA production inhibited?
DNA alkylating agents and topoisomerase inhibitors
How are proteins inhibited?
Tyrosine kinase inhibitors
Monoclonal antibodies
How is microtubule assembly inhibited?
Tubulin-binding drugs
What are examples of alkylating agents & related compounds?
Nitrogen mustards
Platinum compounds
What is an example of nitrogen mustard?
Carmustine
What is an example of platinum compounds?
Cisplatin
What are alkylating gents?
Contain chemical groups that can form covalent bonds with particular substances in the cell, DNA, RNA & proteins
What are some of the side effects of alkylating agents?
They kill rapidly proliferating normal cells and also kill non-proliferating cells because of the bond they create with the DNA, RNA and proteins
What are the examples of cytotoxic antibiotics?
Anthracyclins
Bleomycins
What is an example of anthracyclins and bleomycin?
Anthracyclins: doxorubicin
Bleomycins: bleomycin
What are the cytotoxic agents?
Drugs that owe their antineoplastic actions to their interactions with DNA (intercalation and cross-linking)
Hormones and Hormone Antagonists are an example of:
Endocrine Therapy of Cancer
Which tumors might be hormone-dependent?
Tumors derived from hormone-sensitive tissues like breast and prostate
Growth of hormone dependent tumors can be inhibited by: ?
Hormone antagonists
Agents inhibiting the synthesis of relevant hormones
What are examples of Hormone antagonists?
Tamoxifen in breast cancer
What are examples of agents that inhibit the synthesis of relevant hormones?
Aromatase inhibitors that block oestrogen synthesis in breast cancer
What is an example of aromatase inhibitor?
Anastrozole
What is the main advantage of endocrine therapy?
Far fewer serious adverse effects than cytotoxic agents
What are examples of antimetabolites?
Folate antagonists
Pyrimidine analogues
Purine analogues
What is an example of folate antagonists?
Methotrexate
What is an example of pyrimidine analogues?
5-fluorouracil
What is an example of purine analogues?
6-mercaptopurine
What are anti-metabolites?
They are structurally related to normal cellular components, for instance metabolites for DNA synthesis
What is the MOA of anti-metabolites?
They interfere with the availability of normal metabolites. Inhibit utilisation of the natural metabolite, for instance; DNA synthesis
What is folic acid?
An essential dietary factor that is converted by DHFR to a series of FH4 co-factors that are required fro the synthesis of DNA and RNA
How do anti-metabolites (folate inhibitors specifically like Methotrexate) relate to folic acid and DNA synthesis?
Anti-folates inhibit DHFR and thus DNA synthesis and replication.
What are the side effects of Methotrexate?
Can lead to hematological disturbances like anemia that mimic folic acid deficiencies
What is the solution for the Methotrexate disadvantage?
Administering Folinic acid which by-passes the inhibited DHFR enzyme
What is the name of the Folinic acid?
Leucovorin
Tubulin/Microtubule Binding Agents are examples of:
Mitotic Inhibitors
What are examples of Tubulin/Microtubule binding agents?
Vinca Alkaloids
Taxanes
What are examples of Vinca Alkaloids?
Vincristine and Vinblastine
Where are vincristine and vinblastine found?
Periwinkle plant
What is the MOA of Vinca alkaloids?
They bind tubular & prevent its polymerization into microtubules
Prevention of spindle formation in cells at mitotic stage
Cells are arrested at metaphase
Cells cannot complete mitosis and die
what is an example of taxanes?
Paclitaxel
What is the MOA of taxanes?
Microtubules are stabilised by taxanes:
Taxanes bind to microtubules and inhibit depolymerization into tubules.
Cells remain in metaphase
Cannot divide into daughter cells
Where do taxanes come from?
Yew tree
What is the function of Topoisomerase Enzymes?
Topoisomerase I and II are necessary for DNA replication
What is the function of Topoisomerase Inhibitors?
They cause irreversible DNA breaks, leading to apoptosis and anti-cancer effect
What are examples of Topoisomerase I Inhibitors?
Camptothecins
What are examples of Camptothecins?
Topotecan & Irinotecan
What are examples of Topoisomerase II Inhibitors?
Epipodophyllotoxins
What are examples of Epipodophyllotoxins?
Etoposide & Teniposide
What are Miscellaneous Anti-neoplastic Drugs?
Biological or Targeted Therapies
What are examples of Biological or Targeted Therapies?
Angiogenesis Inhibitors
Tyrosine Kinase Inhibitors
Monoclonal Antibodies
Immunotherapies
What is an example of angiogenesis inhibitors?
Avastin
What is the function of angiogenesis inhibitors?
Designed to stop tumors from developing a blood supply which is a pre-requisite for tutor growth and metastasis
What are examples of tyrosine kinase inhibitors?
Imatinib and Geftinib
What is the function of tyrosine kinase inhibitors?
Inhibition of phosphorylation of growth-promoting proteins
What is an example of monoclonal antibodies?
Trastuzamab
What is the function of monoclonal antibodies?
Neutralise the actions of growth factor receptors signalling that promote cancer growth
Example: HER2 in breast cancer
What is an example of Immunotherapies?
Interferon; Checkpoint Inhibitors
What is the function of immunotherapies?
Designed to boost the body’s natural defense to fight cancer
