7. Chemotherapy Flashcards
why are drugs stimulating the cell cycle sometimes used in chemo?
To increase no. of cancer cells in cell cycle rather than G0 (in which chemo has no effect as targets actively dividing cells)
what is the fractional cell kill hypothesis?
Delivering chemo in pulses to improve tolerance of treatment: chemo kills both cancer cells and bone marrow cells but bone marrow cells recover faster. So give a pulse of chemo as soon as BM cell pop has recovered but not the cancer cells to gradually decrease cancer cell pop.
Overtime, BM cell pop will also decrease but not as much as cancer cells.
name the 4 main types of chemo drugs
- antimetabolites
- alkylating agents
- intercalating agents
- mitotic inhibitors
how do antimetabolites promote cancer cell death
Affect DNA synthesis:
- 5-fluorouracil - inhibits thymylate synthase… pyrimidines not incorporated into DNA strand
- methotrexate - inhibits dihydrofolate reductase… purines not produced
how do alkylating agents promote cancer cell death
Affect DNA replication:
Create inter- and intra-strand adducts (bonds) between 2 DNA strands… inhibit DNA replication… ss and ds breaks
how do intercalating agents promote cancer cell death
Affect DNA replication and transcription:
Bind to DNA strands between bases… affect DNA structure preventing function of DNAP and other DNA-binding proteins… prevent DNA replication/transcription
how to mitotic inhibitors promote cancer cell death
Affect mitosis (spindle poisons):
Are microtubule-binding agents that affect MT dynamics in 2 ways:
- inhibit polymerisation… prevents spindle formation (vinca alkaloids)
- stimulate polymerisation and prevent depolymerisation… inhibit mitosis progression (taxoids)
describe 3 ways in which cancer cells can become resistant to alkylating agents
- enhanced DNA repair mechanisms
- cell membrane pump causes chemo efflux
- inactivation of agent in plasma, e.g. by protein binding (e.g. glutathione)
name 6 factors that affect chemotherapy regimen
- type of cancer: some are very sensitive (e.g. lymphoma, small cell lung) some are very poorly sensitive (e.g. prostate, renal, endometrial, brain)
- performance score: general condition of P (0 = normal - 5 = death) only give in P at 0-3 score
- clinical stage
- prognostic factor/score (often involving biological factors)
- molecular/cytogenic markers
- side effects vs anticipated/best outcome
suggest different routes of administration for chemo
- IV: most common (bolus, infusional bag, continuous pump)
- PO: convenient, dependent on oral bioavailability
- SC: convenient in community setting
- into body cavity, e.g. bladder, pleural effusion
- intralesional: directly into cancerous area, consider pH
- intrathecal: into CSF by lumbar puncture or omaya reservoir (direct into ventricles)
- topical: applied to skin
- IM rarely
suggest examples chemo of side effects
- alopecia
- mucositis (anywhere in GI tract)
- pulmonary fibrosis
- cardiotoxicity
- nausea/vomiting
- diarrhea
- cystitis
- renal failure
- sterility
- myalgia
- neuropathy
- myelosuppression
- phlebitis
describe 3 adverse effect of chemo caused by direct impact of treatment on tumour
- acute renal failure (often multifactorial) - rapid tumour lysis… hyperuricaemia… precipitation of urate crystals in renal tubules
- GI perforation at site of tumour (reported in lymphoma)
- DIC, e.g. onset within a few hours of starting treatment for acute myeloid leukaemia
describe 2 ways in which chemo can be cardiotoxic
- cardiomyopathy
2. arrhythmias
why should Ps who have received bleomycin treatment carry a card stating this?
As they should not receive O2 therapy (e.g. if presenting to AandE with SOB) - bleomycin is toxic to lungs, causing pulmonary fibrosis - worsened by O2
name 3 factors that need to be taken into account when dosing chemo
- surface area and BMI
- drug handling ability (e.g. liver and renal function)
- general wellbeing - performance status and comorbidities
