Chemo and Immunotherapy Flashcards
What systemic therapy can be offered for cancer
Chemotherapy
Biologics
Hormonal therapy
Immunotherapy
What are aims of Rx
Adjuvant
Neoadjuvant
Palliative
Curative or radical
What is adjuvant
After definite and curative `rx to eradicate micromets
What is neoadjuvant
Adjuvant Rx given before to improve change of care
What are SE of chemotherapy
Relate to rapidly dividing tissue as that is what is attacked Vomiting - prophylaxis usually given Alopecia Mouth ulcer Diarrhoea Neuropathy Neutropenia most common 7-14d Thrombocytopenia Infertility - impaired spermatogenesis or oocyte depletion leading to premature failure
What are major classes of systemic chemotherapy
Alkyslating agent - disrupt DNA integrity Anti-metabolites - disrupt DNA synthesis Mitotic inhibitor Toposomerase inhibitor Other anti-tumour Ax
What are antimetabolites and what do they do
Disrupt DNA synthesis by interfering with metabolism Methotrexate Fuorouracil (5-FU) 6-mercaptopurine Cytrabine
What are aklyating agent and what do they do
Disrupt DNA integrity
Cyclophosphamide
Cisplastin
What is mitotic inhibitor
Vinca alkaloid
Taxanes
What is topoisomerase inhibitor / Ax
Doxorubicin - inhibit DNA and RNA synthesis
Etoposide
Irontecan
Anti-tumour Ax
Bleomycin - degrade DNA
Actinomycin
Doxorubicin
How are chemo used
Most chemo combined into regimens to achieve better kill
Must have different mechanism and no overlapping toxicity
What are SE of cyclophosphamide
Haemorrhagic cystitis
Myelosuppression
TCC
SE of doxorubicin
Cardiomyopathy
SE of bleomycin
Pulmonary fibrosis
SE of methotrexate
Myelosuppression Mucositis Liver fibrosis Lung fibrosis Teratogenic B12 defiecicny
SE of 5-FU
Myelosuppression
Mucositis
Dermatitis
SE of other anti-metabolites
Myelosuppression
Ataxia
What does vinblastine / docetaxel do and what are SE
Inhibit formation of microtubule Peripheral neuropathy Paralytic ileus Myelosuppression Neutropenia = docetaxel
Other chemotherapy agents
Cisplastin
Hydroxyurea
SE of cisplatin
Ototoxicty
Peripheral neuropathy
HypoMg
What do biologic agents do and what are there categories
Inhibit orogenic stimulus that is driving cancer growth
Monoclonal Ab - imab
Tyrosine kinase inhibitors - inib
What is ritixumab useful for
Anti-CD20 so useful in NHL - B cell lymphoma which express
What has revolutionised CML Philadelphia chromosome +ve
Tyrosine kinase inhibitor - Imatinib
What causes ligand inactivation
Bevacilumab
Stops VEGF which is over expressed in many cancer
What cause receptor inactivation
Tratuzumab against HER-2
What hormone therapy in breast
Anti-oestrogen / SERM - tamoxifen
Aromatose inhibitor
GnRH agonist (goserelin)
What hormone therapy in prostate cancer
Androgen suppression - goserelin or orchidectomy
Anti-androgen
What hormone therapy in endometrial
Progesterone
What is systemic immunotherapy
Stimulates whole immune system
Interferon
Interluekin
What are toxicity interferon
Flu like Nausea Lethargy Anorexia LFT
What are toxicity IL
Hypotension
Renal failure
Cardiac - may need ITU
How do many cancers evade detection
Suppress T cell function through PD-1 on T cell or PDL-1 on tumour
What Ab target this
PD-1 Ab - nivolumab / pemprolizumab = immune checkpoint inhibitors
PDL-1 Ab - atezolizumab
Used in solid organ tumour
How do you administer
Injection
IV infusion
What are SE related to overactive T cells which are key in killing cancer / SE immunotherapy
Dry / itchy skin = most common N+V Decreased appettite Diarrhoea Fatigue SOB Dry cough
Infusion reaction
Anaphylaxis
How do you manage SE
Corticosteroid
Monitor LFT, U+E, TFT
How does RT work
Produce free radicals which cause DNA damage
Leads to chromosomal aberration
No loss of genetic materally
Lose reproductive capability
What is radiation dose
Energy deposited per unit mass = absorbed dose (Gray)
1 gray = 1 joule of energy in 1kg
What is radiation tolerance
Amount of radiation tissue can receive and still remain functional
What is tolerance dose
Dose that there is a high probability of serious Rx compliction
What is AIM of Rx
High enough dose to achieve outcome whilst keeping critical nearby structure within radiation tolerance
What does radical Rx tend to be
Curative intent
High dose
Low dose fraction as longer timeframe to minimise damage
What is palliative Rx
Lower dose
High dose fraction as late effects less relevant
Short time
What gives more damage
High dose per fraction
How can RT be delivered
External beam Stereotactic - highly accurate form of EBRT for small lesions e.g. intracranial Brachytherapy sealed source Brachytherapy unsealed Radioisotope
What is external beam
Most common
Linear accelerator delivers X-ray
What can you do for deep tumour
Multiple field technique
As single radiation would over treat superficial tissue
What is bradytherapy sealed source
Radioactive needle or wire implanted into or next to cancer for extremely high dose
What is unsealed source
Radioactive isotope delivered by injection or ingestion which concentrates in region
What do all patients with metastatic disease of unknown primary get
FBC, U+E, LFT, Calcium Urinanalysis LDH AFP + hCG CT CAP
What do specific patient get
Myeloma screen if lytic bone Endoscopy PSA CA125 if peritoneal / ascites Testicular USS Mammography
What does a PET scan do
Uses FDG radio tracer allowing 3D image of metabolic activity / uptake of glucose
Combines images with CT
What is it useful for
Evaluating primary and metastatic disease
What do you do if risk of infertility
Semen cyropersevation
Embro / oocyte preservation
What are early reactions to RT
Tiredness Skin reaction - erythema, desquamation, ulceration Mucositis N+V if stomach / liver or brain Rx Diarrhoea after abdominal or pelbic Dysphagia following thoracic Cystitis after pelvic
What can you do for N+V
Anti-emetic
What do you do for mucositis
Avoid smoking
Anti-septic mouthwash
What are late reaction to RT
Secondary cancer
Fibrosis of organs
Reduced fertility
Hypopituitarism / hypothyroid Erectile dysfunction / stenosis following pelvic RT Benign strictures of GI tract Radiation proctitis Pneumonitis Myelopathy
What are chronic risks of chemo
Organ imapirment - may need ECHO / bone density scan
Reduced fertiltiy
Second cancer
What are the RCHOP drugs
Rutixumab Cyclophosphamide Doxorubicin hydrochlroide Vincristin Prednisolone
What is it used to treat
NHL
SE of rutiximab
Allergy - fever / rash / anaphylaxis Severe infections / reactivation Thrombocytopenia Liver and lung toxicity Peripheral neuropathy Night sweats
What is metabolically demanding tissue
Brain
Heart
Liver
What is mitotically
Bone marrow
Skin
Gut
Aim of chemo to target mitotically active cells so SE
Cytopenia and neutropenic sepsis
Sore skin + mouth
N+V+D
Why is it important to get rid of all cancerous cells with first round
If relapse will have a selected cell line that is resistant to chemo
What are outcomes after Rx
Partial remission
Complete remission where cells undetectable (but still there)
Incurable but can control for long term
What is important to remember
Will be cells that never undertake mitosis when getting chemo so never get killed and can come back when start division
How do you treat pre-malignant conditions e.g. myelodysplasia
Low dose continuous therapy e.g. hydroxycarbamdie everyday
Rx of ALL. /AML
Potentially curable
If relapse = very bad sign
If in remission for a few years chances its gone for good as cells would have come back
Rx of CLL / CML
Less chemo sensitive as undergo mitosis less often
Usually monitor till cause problem / system
Rx = usually chemo based
