Chemotherapy in the clinical setting (DONE) Flashcards
The cell cycle
This is the process by which cells reproduce and develop Consists of 5 phases: Resting phase (G1) Preparation DNA synthesis (S) Resting state (G2) Division (M)
How can chemotherapy be delivered?
Oral, IV, SC, IM, intrathecal, intra-vitreal, intravesical, topical, intraperitoneal, intrapleural
Cell cycle specific chemotherapy agents
As all cells are not in cycle at the same time they are best given by repeated dosing or by continuous infusion
Examples: anti-metabolites, vinca alkaloids, topoisomerase inhibitors, taxanes
Cell cycle non specific chemotherapy agents
Cytotoxic agents that are effective throughout all phases of the cell cycle
They directly affect the DNA molecule
Show no specificity to dividing cells- thought to be more toxic that cell cycle specific
Tend be given as bolus doses
Examples: alkylating agents, antitumour antibiotics, platinum compounds
Advantages of combination therapy
Choose drugs with different side effects for maximum effect with minimum toxicity
Broader range of coverage for resistant cells
Less development of new resistant cell lines
Synergistic effects
CMF (breast cancer)
Cyclophosphamide
Methotrexate
Fluorouracil
R-CHOP (non-Hodgkins lymphomas)
Rituximab Cyclophosphamide Doxoxrubicin Vincristine Prednisolone
R-CVP (B-cell lymphoma)
Rituximab
Cyclophosphamide
Vincristine
Prednisolone
Preventing adverse effects
Appropriate doses
Doses related to weight/surface areas
Appropriate combinations of drugs
Recovery time between cycles
Adverse effects
Infection, bleeding, anaemia Nausea and vomiting Mucositis Alopecia Infertility Secondary malignancy Extravasation Tumour lysis Drug-specific
Infection in bone marrow
White blood cells destroyed
Severity and duration of myelosuppression is drug dependent
Can predict when patient is most susceptible to infection
Nadir
Lowest absolute neutrophil count after chemotherapy
Usually 10-14 days
Risk of infection
Neutrophils <1.0 associated with significant morbidity and mortality from infection
Prolonged neutropenia increases risk
At risk from bacteria, virus and fungi
Minimising the risk of infection
Good hygiene
Prophylactic anti-infectives e.g. ciprofloxacin
Haematopoietic growth factors e.g. G-CSF
Monitor own temperature at home and act on high readings
Aseptic technique when handling IV catheter siites
Lifestyle advice
Mouth hygiene
Brush teeth regularly
Soft toothbrush
Antiseptic mouthwash
Haematopoietic growth factors
Limit severity and duration of neutropenia
Reduce risk of infection and avoid treatment delays
Support neutrophils, allow higher doses
Do not prevent neutropenia after chemotherapy
No evidence of improved overall survival
E.g. filgrastim, lenograstim
Bone marrow/stem cell transplant
Destruction of the bone marrow restricts doses of chemotherapy that can be used
Bone marrow contains stem cells
Stem cells can also be found in the peripheral blood after chemotherapy or G-CSF
Can give high doses of chemotherapy, then transplant stem cells into patient
Used as a treatment for haematological malignancies such as myeloma, leukaemia and lymphoma
Treatment of infection
Treat any fever with broad spectrum antibiotics
Cytotoxic drugs compromise ability of patient to fight infection
Reduce by using prophylactic antibiotics whilst patient is neutropenic and giving lifestyle advice
How to treat infection
Immediate broad spectrum IV antibiotics e.g. tazocin and gentamicin
Review daily, responding to positive isolates and clinical signs
Consider unusual infections
Refer any patient feeling unwell during nadir period
Consider interactions of OTC meds with chemotherapy
Thrombocytopenia
Less common than neutropenia
May occur 7-14 days after chemotherapy
Causes bleeding
Management: avoid IM injections, women receive norethisterone, platelet transfusion, tranexamic acid
Anaemia
Rare effect due to long life span of circulating RBCs (120 days)
Management: blood transfusion
Marrow recovery
FBC must be checked before each cycle
Dose reduction or treatment delay if marrow recovery has not occurred
Nausea and vomiting
Common
Profound effect on QoL
Many recent advance in control of N and V
Anticipatory emesis is now less common due to better symptom control
Delayed emesis remains a problem
Risk factors for N and V
Emetogenic potential of chemotherapy drugs Previous experience of chemotherapy Female gender Under 50 years old Low alcohol intake Anxiety
Anti-emetic drugs
5HT3 antagonists: granisetron, ondansetron, tropisetron
Standard antiemetics: cyclizine, metoclopramide, Domperidone
Aprepitant
Dexamethasone
Lorazepam
Levomepromazine
5HT3 antagonists
Block 5HT3 receptors in CTZ Highly effective More effective if combined with dexamethasone Oral or IV Less effective for delayed N and V
Aprepitant
Neurokinin 1-receptor antagonist
Licensed to treat N and V caused by chemotherapy
IV form = fosaprepitant
Dexamethasone
Most effective available agent for delayed emesis
Given in combination with other anti-emetics for regimens of high emetogenicity
Lorazepam
Useful for anticipatory N and V
Amnesic, sedative and anxiolytic effects
May be given IV or sub-lingually
Levomepromazine
Phenothiazine derivative
Good for delayed emesis
Can be given as an SC infusion
Mucositis
Symptoms: ulceration, pain, tingling, dry mouth, loss of taste
May affect whole GIT
Easier systemic access for bacteria and fungi present in the mouth
May develop 3-4 days after chemotherapy
Management of mucositis
Good oral hygiene
Regular use of antiseptic mouthwash
painkillers- mouthwashes, oral, injection
Calcium folinate with MTX
Alopecia
Drug dependent e.g. etoposide
Reversible
Scalp cooling techniques- of little benefit
Wigs available on NHS
Male infertility
Azospermia and infertility common (esp. alkylating drugs e.g. cyclophosphamide)
May be permanent
Sperm banking
Pre-treatment counselling
Female infertility
Amenorrhoea and sterility can occur
Ovarian function may be restored
Premature menopause
Pre-treatment counselling
Secondary malignancy
Affects mainly children
Especially with alkylating agents
Most common secondary malignancies are all lymphoma
Extravasation
Vesicant drug leaks out of vein into surrounding tissue
May require plastic surgery
Should always be treated as an emergency
Management of extravasation
Avoid by: regular observation, using central lines
Treat by: stopping infusion, drawing back if possible, flushing site and using antidotes
Tumour lysis
Treatment of bulky, fast growing disease- large amount of waste products
Accumulation causes acute renal failure
Mainly associated with acute leukaemias and high grade lymphoma
Prevent with hydration, allopurinol, rasburicase
Renal toxicity
Cisplatin, ifosfamide, methotrexate, carboplatin, cyclophosphamide
Prevention: maintain diuresis > 100ml/hour, monitor urea and creatinine
Haemorrhagic cystitis
Potential side effect of ifosfamide and cyclophosphamide (high dose) drug metabolite scours the bladder epithelium
Management: mesna- reacts with acrolein in the urinary tract to form harmless compound, high fluid intake
Electrolyte disturbances
Cisplatin: electrolyte leaching occurs- Mg, Zn, Ca and K- manage with IV electrolyte and fluid supplements
High dose 5-FU: hypokalaemia- manage with oral/IV supplements
Cardiac toxicity
Especially with anthracyclines e.g. doxorubicin, daunorubicin
Causes cardiomyopathy and heart failure
Minimise by setting maximum cumulative dose
Neurotoxicity
Vinca alkaloids e.g. vincristine can cause nerve damage
Patients report tingling or numbness of fingers/toes, constipation
Use alternative vinca alkaloid, or withhold
Hypersensitivity/infusion reactions
Occurrence increasing with use of monoclonal antibodies
Regularly seen with taxanes and rituximab
Infusions should be started very slowly
Cover with steroids and antihistamines
Close observation by nurses trained to respond
Hand-foot syndrome
Occurs during treatment with 5-FU
Treat with pyridoxine and emollients
Drugs used specifically to prevent induced side effects
Calcium folinate (folinic acid) Rescue from methotrexate- speeds recovery from methotrexate induced mucositis and myelosuppression Given in repeated doses over at least 2 days, start 24 hours after beginning of methotrexate infusion
