Oncology: Chemotherapy Flashcards
give some systemic treatment options for cancer
- Cytotoxic chemotherapy
- Hormone therapy
- Biological antibodies (monoclonal - end in MAB, tyrosine kinase inhibitors - end in IB)
- Immunotherapy
- Radioactive isotopes
What does ‘radical’ mean in cancer management?
Curative intent
What cells does chemotherapy act on?
As these agents act on rapidly dividing cells, certain groups of cells are disproportionately affected.
What are the key immediate side effects of chemotherapy?
1) Bone marrow suppression (haematopoietic suppression)
2) Nausea/vomiting
3) GI upset e.g. mucositis, diarrhoea
4) Alopecia
5) Neurological e.g. peripheral neuropathies, ototoxicity
6) Genitourinary e.g. nephrotoxicity, bladder toxicity
7) Cardiac e.g. arrhythmias, coronary artery spasm
8) Skin and soft tissue e.g. extravasation, palmar plantar erythema (hanf-foot syndrome), photosensitivity, pigmentation
9) Hepatic e.g. transient rise of liver enzymes, rarely fulminant hepatic failure
10) Others e.g. lethargy, myalgia, arthralgia, allergic reactions
Features of haematopoietic suppression as a result of chemotherapy?
Anaemia, thrombocytopenia, leukopenia
What is neutropenic sepsis?
How is it defined?
Defined as a neutrophil count of 0.5 × 109 per litre or lower, plus one of the following:
1) Temperature ≥ 38°C
OR
2) Other signs or symptoms consistent with significant sepsis
What is the most common medical emergency amongst oncology and haematology patients?
Neutropenic sepsis
What are the GI effects of chemotherapy?
Increased apoptosis within the rapidly dividing epithelial cells in the oral mucosa and intestine causes mucosal damage throughout the GI tract.
Symptoms; mucositis, malabsorption and diarrhoea.
How can chemotherapy cause N&V?
The direct effect of some chemotherapy agents on the chemoreceptor trigger zone within the medulla can cause severe nausea and vomiting.
How can chemotherapy result in hair loss?
Chemotherapy-induced damage to the rapidly dividing cells in the hair root results in hair loss.
What is mucositis?
Mucositis is inflammation of the mucosa, the mucous membranes that line your mouth and your entire gastrointestinal tract.
What are the benefits of giving chemotherapy drugs in combination?
- Different actions → kill more cells ‘synergism’
- Decrease chance of resistance
- Different sites of toxicity (dose maintained for each drug)
N.B. Single agent chemotherapy may be appropriate
in the palliative setting
What can be given to help N&V in chemotherapy?
5-HT antagonists e.g. ondansetron
Who is at increased risk of oral mucositis in chemo?
Diabetics
What 2 types of chemotherapy drugs can cause cardiomyopathy?
1) Anthracyclines
2) HER-2 monoclonal antibodies
Give 2 examples of anthracyclines
1) doxorubicin
2) daunorubicin
What type of chemotherapy agents can cause peripheral neuropathy and sensorineural hearing loss?
Platinum agents (cisplatin, carboplatin)
What type of chemo agents can lead to haemorrhagic cystitis and transitional cell carcinoma of the bladder?
Cyclophosphamides
Key risk factor of tamoxifen?
increased risk of endometrial cancer
Key risk factor of bleomycin?
lung fibrosis
Key risk factor of cisplatin?
1) ototoxicity
2) nephrotoxicity
Key risk factor of cytarabine?
ataxia
What is bleomycin?
A type of chemo drug –> is an antibiotic that is poisonous to cells.
What type of cells usually respond best to chemotherapy?
rapidly proliferating cells
Define neoadjuvant chemotherapy
PRE-operative treatment of an operable tumour before definitive surgical
Aim of neoadjuvant chemo?
a) to make the tumour smaller
b) to allow less radical surgery
c) treating occult micro metastases at the same time
i.e. aims to increase cure rates
For what cancer is neoadjuvant chemo established?
Osteosarcoma
Define 1ary chemo
Aim?
Initial chemotherapy for a tumour that is inoperable or of uncertain operability, where a reduction in the tumour bulk in a pre-defined manner may make surgery with curative intent feasible.
Aim - increase cure rates
Define adjuvant chemo
Aim?
The use of chemotherapy AFTER a complete surgical macroscopic clearance.
Chemotherapy in this setting treats the occult microscopic metastases which we know usually lead to relapse after surgery for lymph-node positive disease (e.g. breast cancer and colorectal cancer).
Aim - increase cure rates
Aim of palliative chemo?
This is treatment to alleviate symptoms and in some cases prolong life in patients who cannot be cured.
Must be balanced so that the patient’s quality of life is not made worse by the treatment
When would prophylactic chemo be used?
Hormonal treatments may be given before overt malignancy appears.
E.g. tamoxifen may be used for in-situ breast cancer before invasive carcinoma is recognised.
Different route of administration of chemo drugs:
1) Orally
2) Systemically
3) Regionally e.g. intravesical, intraperitoneal, intra-arterial
When is intravesical chemo routinely given?
Management of superficial bladder cancer
Advantages of intravesical chemo?
Producing high doses at the site of the tumour, with negligible systemic absorption and hence minimal systemic toxicity.
When may chemo be administered directly into the peritoneal cavity (i.e. intraperitoneal)?
in the context of tumours that spread trans-coelomically (e.g. ovarian cancer)
When may chemo be delivered intra-arterially?
Any tumour that has a well-defined blood supply is potentially suitable for intra-arterial chemotherapy (e.g. hepatic artery infusion for liver metastases).
This allows higher doses to be delivered to the involved site and reduces systemic toxicity.
What is the one chemo drug to have its dose calculated directly according to the renal function?
Carboplatin
How are routine cytotoxic chemotherapy doses calculated?
According to the patient’s body surface area.
Most most commonly used formula is that of DuBois and DuBois
Chemotherapy causes bone marrow suppression which can lead to leucopenia and thrombocytopenia.
What is the lowest point in this drop called?
The nadir
GI side effects of chemo?
- Diarrhoea; due to colitis or small bowel mucosal inflammation.
- Oral mucositis
- Constipation
What typically causes constipation in chemo?
1) dehydration with reduced oral intake due to nausea
2) result of adverse effects of other medications being taken such as opiate analgesics or 5-HT antagonists
3) rarely a paralytic ileus can develop due to autonomic neuropathy after platinum agents or vinca alkaloids.
In some cases, what can alopecia caused by chemo be controlled by?
a cold cap which reduces the blood flow to the scalp
What are some neurological side effects of chemo?
1) Peripheral neuropathies
2) Autonomic neuropathy
3) Central neurological toxicity
4) Ototoxicity
What is the aim of radiotherapy?
The aim of radiotherapy is to deliver carefully calculated doses of radiation to cancer cells, whilst minimising the radiation exposure to surrounding tissues
How is radiotherapy used in the treatment of cancer?
Can be the sole treatment (e.g. prostate cancer).
Can be used alongside surgical management:
a) neoadjuvant (i.e. prior to surgery)
b) intraoperative (i.e. during surgery)
c) adjuvant (i.e. after)
Radiotherapy can play an important role in the palliation of symptoms for cancer patients.
Give some examples of this
1) Radiotherapy to a tumour causing spinal cord compression (thus reducing neuropathic symptoms)
2) Radiotherapy to bony metastasis to reduce pain
How does radiotherapy work?
Radiotherapy uses high energy radiation to eliminate cancer cells.
The radiation used is ionising, meaning it forms ions (charged particles) which then deposit energy into the cells of the tissues they pass through.
This causes cell death.
Radiation causes cell death in one of which two ways?
1) Triggering direct cell apoptosis by causing significant DNA damage
2) Preventing cancer cell proliferation, by causing single and double-stranded breaks in DNA (known as mitotic cell death)
How is radiotherapy delivered?
Radiotherapy is delivered in fractions (i.e. sessions) until the total prescribed cumulative dose has been delivered.
What is the amount of energy absorbed in radiotherapy measured in?
Grays (commonly abbreviated as Gy)
Purpose of fractionation in radiotherapy?
Fractionation helps to reduce the risk of acute tissue reactions and minimises damage to normal cells (which are better able to undergo repair between fractions).
What are some long term complications of chemo?
1) Second malignancies
2) Fertility
3) Pulmonary e.g. fibrosis, pneumonitis
4) Cardiac e.g. cardiac fibrosis
5) Psychological and social e.g. employmemt, insurance, relationships
Which chemo drug is ototoxic?
Cisplatin –> can cause cochlear damage and high tone hearing loss (permanent)
What 2 chemo drugs are associated with acute arrhythmias?
1) Doxorubicin
2) paclitaxel
What is palmar plantar erythema (Hand-foot syndrome)?
Hand-foot syndrome causes redness, swelling, and pain on the palms of the hands and/or the soles of the feet. Sometimes blisters appear.
What are the 2 most carcinogenic chemo drugs?
- Alklyating agents
- Procarbazine
How can chemo affect fertility?
Most chemotherapy drugs are associated with a reduction in fertility.
- Male patients receiving chemotherapy likely to cause infertility should be considered for sperm storage
- For female patients it is possible to store fertilised ova and cryopreservation of sections of ovary
Which chemo drug is most likely to cause infertility?
alkylating agents
How does chemo affect the bone marrow?
- Transient fall in leukocyte and platelet count
- Lowest point (the nadir) generally occurs at about 10 to 12 days
How can anaemia in chemo/cancer be managed?
- Blood transfusions
- Use of recombinant erythropoetin
What are the clinical signs of significant thrombocytopenia?
1) Petechial haemorrhage
2) Spontaneous nose bleeds
3) Corneal haemorrhage
4) Haematuria
What examinations should be done in neutropenic sepsis?
Which should NOT be done?
Careful physical examination to look for potential sites of infection is indicated
Rectal and vaginal examinations should not be done because of the risk of causing bacteraemia if the mucosa is breached.
Investigations in neutropenic sepsis?
Extensive cultures of blood, urine, sputum, throat etc. and a chest X-ray are taken, and may influence subsequent changes to antibiotic therapy.
Abx management in neutropenic sepsis?
- 5 days broad spectrum
- Failure to respond in 48 hours indicates need to change to 2nd line
What are some side effects of immunotherapy drugs?
- Rash
- Pneumonitis (lung inflammation)
- Diarrhoea/colitis
- Hepatitis
- Nephritis
- Myalgia/arthralgia
- Endocrinopathies
Presentation of pneumonitis?
- Dry cough
- SOB
- Reduced exercise tolerance
- Fatigue
Management of pneumonitis?
Oral steroids (if signs of infection, treat this first)
What endocrinopathies are seen in immunotherapy treatment?
- Thyroid disorders
- Pituitary inflammation (hypophysitis) –> can cause wide range of hormone abnormalities e.g. adrenal insufficiency, 2ary hypothyroidism
At what time is serum cortisol best taken?
9am
How can you formally assess adrenal function?
A short Synacthen test
Management of proven adrenal insufficiency or high clinical index of suspicion?
hydrocortisone replacement
N.B. Adrenal crisis is a life-threatening medical emergency so, if in doubt, consider hydrocortisone and ask for help.
Patients with serious cancer immunotherapy side effects may require weeks or months of high dose steroids or other immunosuppressants to manage these side effects.
What are some potential side effects of long-term steroid immunosuppresion?
- Sleep disturbance
- Weight gain
- HTN
- Increased risk of infection
- Indigestion +/- GI bleeding
What does radiotherapy planning involve?
The process of radiotherapy planning involves using imaging to determine where the radiation is to be aimed, using the principle of maximising the radiation dose to abnormal cancer cells while minimising exposure to normal cells.
What are the 2 primary methods of delivery radiation?
1) External beam radiation
2) Internal radiation (brachytherapy)
How is radiotherapy delivered via external beam radiation?
Delivered from outside the body by aiming high-energy rays (e.g. protons, photons, particle radiation) towards the cancer’s location
What isthe most common radiation delivery method?
External beam radiation
How does internal radiation (brachytherapy) deliver radiotherapy?
Uses radioactive sources in catheters or seeds to deliver radiation from inside the body directly into the tumour site.
As the radioactive sources tend to be placed directly next to the tumour, a high dose of radiation is delivered to the tumour whilst surrounding healthy tissue is exposed to a relatively small dose.
What cancers is brachytherapy often used in the management of?
Cervical and prostate cancer
Do side effects of radiotherapy tend to be systemic or local? What about chemo?
Radiotherapy –> local
Chemo/immunotherapy –> systemic
What are the early side of radiotherapy (i.e. within a few weeks)?
- Skin reactions (erythema, desquamation)
- Fatigue
- Mucositis
- Diarrhoea
- Nausea
These tend to resolve within a few weeks of onset.
What are the late side of radiotherapy (i.e. months to years later)?
- Radiation-induced fibrosis
- Atrophy
- Neural or vascular damage
- A range of endocrine effects (e.g. diabetes, hypothyroidism)
- Small risk of 2ary malignancy due to radiation-associated DNA damage
Later side effects tend to be irreversible and may be progressive.
What are some site specific side effects of head and neck radiotherapy?
Dysphagia
Jaw stiffness
Dry mouth
Mouth and gum sores
Hair loss
Lymphoedema
Tooth decay
What are some site specific side effects of chest radiotherapy?
- Dysphagia
- Dyspnoea
- Radiation pneumonitis: can manifest as cough, chest pain and fevers
- Radiation fibrosis: the result of permanent lung scarring as a result of untreated radiation pneumonitis
What are some site specific side effects of abdominal radiotherapy?
Nausea and vomiting
Diarrhoea
Loss of appetite
Abdominal cramping
What are the key side effects of cisplatin?
- Nephrotoxicity
- Peripheral neuropathy
- Ototoxicity
- Increased risk of infection e.g. fever, muscle aches
- Anaemia e.g. SOB, fatigue
- Diarrhoea
Which class of chemotherapy drugs are known to cause cardiomyopathy?
Anthracyclines (e.g. doxorubicin)
