Cancer chemotherapy Flashcards
Cancer
• Cancer is the second leading cause of mortality
• Continuous uncontrolled growth of cells
• A tumour is any abnormal proliferation of cells
• Benign tumours stays confined to its original location
• Malignant tumours are capable of invading surrounding tissue or
invading the entire body
• Tumours can arise from any cell type in the body and are classified
as to their cell type
Causes of cancer
- Environmental exposure
- Viruses
- Oncogenes
- Tumour suppressor genes
Treatments of cancer
• Surgery or
• Radiotherapy
-mainly possible when tumour remains localised at diagnosis
• Chemotherapy - once cancer metastasizes chemotherapy is
required for effective cancer management.
• Chemotherapy is often combined with radiotherapy to allow
surgical resection to take place.
Number of chemo drugs
More than 100
-either alone or in combination with other drugs or treatments
Chemo drugs vary widely based on
- chemical composition
- route of administration
- type of cancer targeted
- side effects
Primary induction chemo
when it is administered in
patients with advance cancer for which no alternative treatment
exists. Can be curative in only a small subset of patients who present
with advance disease. (i.e. Hodgkin’s and non-Hodgkin’s lymphoma
in adults or lymphoblastic leukemia in children).
Neoadjuvant chemo
in patients with localised cancer
for which alternative local therapies, e.g. surgery, exist but which are
less than completely effective.
Adjuvant chemo
as an adjuvant to local therapy such as
surgery or radiation. Is effective in prolonging both disease-free and
overall survival in patients with different type of cancer (i.e. patients
with breast, colon gastric or non-small lung cancer)
Main goal of antineoplastic agents is
to eliminate the cancer
cells without affecting normal tissues
-in reality, all cytotoxic drugs affect normal tissues as well as
malignancies - aim for a favorable therapeutic index
Therapeutic index
LD50 / ED50
-lethal dose of a drug for 50% of pop (LD50) divided by min effective dose for 50% of pop (ED50)
Chemotherapy: to acheive a cure
TOTAL CELL KILL must be tried
• Early diagnosis and early institution of treatment
• Combination chemotherapy
• Intermittent regimens
• Adjuvant and neoadjuvant chemotherapy occasionally
Log-kill hypothesis
• Chemotherapeutic agents kill a constant
PROPORTION of tumour cell population
(first order kinetics), rather than a constant
NUMBER of cells, after each dose
• Solid cancer tumours – generally have a low
growth fractions thus respond poorly to
chemotherapy and in most cases need to be removed by surgery
• Disseminated cancers- generally have a high
growth fraction and generally respond well
to chemotherapy
Cell cycle
• Several anticancer effective drugs exert their action on cells
traversing the cell cycle and are called Cell Cycle- Specific (CCS)
• Cell-Cycle-Non Specific (CCNS) drugs that can sterilize tumour cells
whether they are cycling or resting in the G0 compartments
Cell cycle drugs
Cell cycle specific (CCS) -antimetabolites (S phase) -taxanes (M phase) -vinca alkaloids (M phase) -antimicrotubule inhibitor (M phase) -antitumous antibiotics (G2-M phase) Cell cycle non specific (CCNS) -alkylating agents -antitumour antibiotics -campothecins -platinum analogs -anthracyclins
Alkylating agents
Carcinogenic in nature and can
increase the risk of secondary
malignancies
Form reactive carbonium ion –> transfer alkyl gps to nucleophilic sites on DNA bases
-cross linkage
-abnormal base pairing
-DNA strand breakage –> reduces cell proliferation
• Used to treat a wide variety of hematologic and solid tumour
(i.e. ovarian cancer, brain tumours)
• Immunosuppressant action
• Most of the adverse effects are generally dose-related and occur
primarily in rapidly growing tissues
• Bone marrow depression
• Nausea and Vomiting. Antiemetics are often given prior and after
alkylating agents dosing