Chemotherapy in the clinical setting (DONE) Flashcards by Siobhan Nickels

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 well did you know this?

Not at all

Perfectly

How can chemotherapy be delivered?

Oral, IV, SC, IM, intrathecal, intra-vitreal, intravesical, topical, intraperitoneal, intrapleural

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

CMF (breast cancer)

Cyclophosphamide
Methotrexate
Fluorouracil

How well did you know this?

Not at all

Perfectly

R-CHOP (non-Hodgkins lymphomas)

Rituximab
Cyclophosphamide
Doxoxrubicin
Vincristine
Prednisolone

How well did you know this?

Not at all

Perfectly

R-CVP (B-cell lymphoma)

Rituximab
Cyclophosphamide
Vincristine
Prednisolone

How well did you know this?

Not at all

Perfectly

Preventing adverse effects

Appropriate doses
Doses related to weight/surface areas
Appropriate combinations of drugs
Recovery time between cycles

How well did you know this?

Not at all

Perfectly

Adverse effects

Infection, bleeding, anaemia
Nausea and vomiting
Mucositis
Alopecia
Infertility
Secondary malignancy
Extravasation
Tumour lysis
Drug-specific

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Nadir

Lowest absolute neutrophil count after chemotherapy

Usually 10-14 days

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Mouth hygiene

Brush teeth regularly
Soft toothbrush
Antiseptic mouthwash

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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 well did you know this?

Not at all

Perfectly

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 ```