Principles of cancer chemotherapy Flashcards
Drug classes under anti-cancer chemotherapeutic agents
1. Cytotoxic agents
a) alkylating agents
b) anti-metabolites
c) cytotoxic antibiotics
d) plant derivatives
2. Hormonal therapy
a) hormone analogues
b) hormones antagonist
3. Kinase inhibitors
a) tyrosine kinase inhibitors
b) other kinase inhibitors
c) pan-kinase inhibitors
4. Monoclonal therapy
5. miscellaneous agent
Under drug class ‘cytotoxic agents’, there are
a) alkylating agents
-nitrogen mustard: cyclophosphamide
-nitrosourea: carmustine
-platinum compounds: cisplatin
b) anti-metabolites
-folate antagonist: methotrexate
-pyrimidine pathway antagonist: fluorouracil
-purine pathway antagonist: mercaptopurine
c) cytotoxic antibiotics
-anthracyclines: doxorubicin
-others: bleomycin
d) plant derivatives
-taxanes: paclitaxel, docetaxel
-vinca alkaloids: vinblastine, vincristine
-others: etoposide
Under cytotoxic agents, alkylating agents are cell cycle specific or non specific?
Cell cycle non-specific
MOA of alkylating agents
intra-strand linking and cross-linking of DNA
interferes transcription and DNA replication
resulting in inhibition of DNA synthesis and function
MOA of alkylating agent: cyclophosphamide
reacts with guanosine moieties in DNA
cross-linking, mismatch, damage
cytotoxic effect
therapeutic uses of cyclophosphamide
- chronic lymphocytic leukaemia
- Hodgkin’s and non-Hodgkin’s lymphoma
- solid tumours
- rheumatoid arthritis with severe systematic manifestations (unlicensed indications)
AE of cyclophosphamide
- Specific toxicity
-acrolein (metabolites of cyclophosphamide) causes HAEMORRHAGIC CYSTITIS aka inflammation & bleeding of bladder
-mesna + acrolein, reduce toxicity - General toxicity
-bone marrow suppression
-GI side effects
-prolonged treatment>acute leukaemia
Under cytotoxic agents, what is the MOA, uses and AE of nitrosourea: carmustine aka mustard gas?
MOA: same as cyclophosphamide
Use: BRAIN CANCER due to lipid soluble, can cross BBB
AE: bone marrow suppression m/c, reduced spermatogenesis, severe rashes leading to Steven Johnson syndrome
MOA of platinum compounds (alkylating agents) under cytotoxic agents (drug class)
cross-link complementary strands of DNA
cross-linking mismatch damage
not cell-cycle specific
cytotoxic effects
Therapeutic uses for cytotoxic agents>platinum compounds: cisplatin
solid tumours
eg. germ cell tumour, bladder, lung, upper GI, ovarian cancer
AE of platinum compounds: cisplatin
-seriously nephrotoxic (MUST HYDRATE, DIURESIS NECESSARY)
-highly emetogenic (VERY SEVERE NAUSEA & VOMITING): ondansetron effective in preventing this
-ototoxic
-hypomagnesaemia
*think of this, ciSPLATin= makes your kidneys go SPLAT=nephrotoxic
MOA, therapeutic use and AE of folate antagonist: methotrexate
MOST WIDELY USED ANTIMETABOLITES
MOA: inhibits DHFR dihydrofolate reductase enzyme & depleting intracellular FH4 tetrahydrofolate
therapeutic use: breast, head & neck cancer; immunosuppressant drug for rheumatoid arthritis
AE: depression of bone marrow, damage to epithelium of GI
**high dose regimen: treat with folinic acid (a form of FH4)
MOA, therapeutic use and AE of pyrimidine pathway antagonist: fluorouracil
MOA: interfere with DTMP thymine monophosphate synthesis by interacting with thymidylate synthetase, resulting in inhibition of DNA
Use: colorectal cancer, solid tumours
AE: GI epithelial damage, MYELOTOXICITY/bone marrow toxicity
MOA, therapeutic use and AE of purine pathway antagonist: 6-Mercaptopurine
MOA: HGPT enzyme converts 6MP to compounds that inhibits new formation of ribosyl 5-phosphate and conversion to adenine & guanine nucleotides. Induces strand breaks & base mispairing
Use: leukaemias
AE: myelosuppression
MOA, use , AE of anticancer antibiotics/cytotoxic antibodies: doxorubicin
MOA: inhibit DNA synthesis by inhibiting topoisomerase II (rapid proliferate cells)
use: breast, lymphoma, solid tumours
AE: CARDIOTOXICITY, alopecia, myelosuppression, stomatitis
MOA, use , AE of anticancer antibiotics: bleomycin
MOA: degrades performed DNA, fragment DNA chains, acts on non-dividing cells
use: germ line cancers
AE: PULMONARY FIBROSIS
MOA of plant derivatives> taxanes: paclitaxel, docetaxel
act on microtubules as mitotic spindle poison
stabilise them in polymerised state
inhibit mitosis & cell division
MOA of plant derivatives> vinca alkaloids: vincristine, vinblastine
inhibit of tubulin polymerization
disrupt assembly of microtubules
results mitotic arrest in metaphase
halting cell division>cell death
IMPORTANT therapeutic uses & common AE of plant derivatives
vincristine!!!!
use: leukemia, hematologic malignancies
AE: neurotoxicity with peripheral neuropathy, myelosuppression, alopecia
paclitaxel
use: solid tumours (eg. ovarian, breast, NSCLC and SCLC)
AE: myelosuppresion, peripheral sensory neuropathy
Plant derivatives>others: etoposide
MOA: inhibit topoisomerase II, result in DNA damage
AE (SEEN IN ALL ANTI-CANCER DRUGS): alopecia/hair loss, myelosuppression
Under drug class ‘ hormonal therapy’, there are
1. hormone analogues长得跟hormone相似
a) glucocortisteroid aka glucocorticoids: prednisolone
b) GnRH analogues: leuprolide
c) oestrogen: diethystilbestrol
d) progestrogens aka synthetic progesterone: medroxyprogesterone
2. hormones antagonist
a) antioestrogens: tamoxifen
b) antiandrogens: flutamide
MOA of hormone analogues: glucocortisteroids & GnRH analogues
glucocortisteroids: prednisolone
-inhibit lymphocyte proliferation, treat leukemias and lymphomas
GnRH analogues: leuprolide
-inhibit gonadotropin release
-treat advanced breast cancer in premenopausal women and prostate cancer
uses of hormone analogues: estrogens & progestrogens
estrogens: diethylstilbestrol
-palliative treatment of androgen-dependent prostatic tumour
progestrogens: medroxyprogesterone
-treat endometrial cancer
uses of hormones antagonists: antioestrogens, antiandrogens, aromatase inhibitors
antioestrogen: tamoxifen
-treat hormone-dependent breast cancer
-competes with endogenous estrogen for estrogen receptors, inhibiting transcription of estrogen-responsive genes
-cause endometrial carcinoma in long term use
antiandrogens: flutamide
-treat prostate tumour (androgen dependent tumuor)
aromatase inhibitors: anastrozole, letrozole
-suppress synthesis of oestrogen from androgens in adrenal cortex
-treat breast cancer in postmenopausal
