Cytotoxic Drugs Side Effects

What is extravasation and why is it dangerous?

• Leakage of IV cytotoxic drug into surrounding tissues

• Causes severe local tissue damage

What are common general adverse effects of chemotherapy?

• Bone marrow suppression

• Oral mucositis

• Nausea and vomiting

• Alopecia

• Thromboembolism

• Reproductive toxicity

• Tumour lysis syndrome

Which cytotoxic drugs commonly cause oral mucositis?

• Fluorouracil

• Methotrexate

• Anthracyclines

How can oral mucositis be prevented?

• Good oral hygiene

• Treat with Saline mouthwashes

• Sucking on ice chips with fluorouracil

Better to prevent then treat

What is used to treat methotrexate-induced mucositis?

Folinic acid (levofolinic acid)

What causes tumour lysis syndrome?

• Rapid destruction of malignant cells

• Releases intracellular contents into bloodstream

Which cancers have the highest risk of tumour lysis syndrome?

• Non-Hodgkin’s lymphoma

• Burkitt’s lymphoma

• Acute lymphoblastic leukaemia (ALL)

• Acute myeloid leukaemia (AML)

Which patient factors increase risk of Tumour Lysis Syndrome?

• Pre-existing hyperuricaemia

• Dehydration

• Renal impairment

What electrolyte abnormalities occur in tumour lysis syndrome?

Increased:

• Hyperkalaemia

• Hyperphosphataemia

• Hyperuricaemia

Decreased:

• Hypocalcaemia

What complications can occur in Tumour Lysis Syndrome?

• Renal damage/failure

• Cardiac arrhythmias

How is hyperuricaemia prevented before treatment?

• Allopurinol started 24 hours before chemotherapy

• Ensure adequate hydration

More present in high grade → Lymphoma and Leukaemia

What is an alternative to allopurinol for Chemotherapy-Induced Hyperuricaemia (Alternative Drug)?

Febuxostat, started 2 days before treatment

When does chemotherapy-induced bone marrow suppression usually occur?

Typically 7–10 days after administration

Methotrexate can cause as well → Use Folinic acid treat toxicity

Which cytotoxic drugs are less likely to cause bone marrow suppression?

• Vincristine

• Bleomycin

What monitoring is required before treatment in bone marrow suppression?

• Check full blood count (FBC)

• Reduce dose if bone marrow has not recovered

Bone Marrow Suppression (Infection Risk) – What should be done if infection occurs?

• Avoid chemotherapy during acute infection

• Seek urgent medical attention

• Neutropenic fever → broad-spectrum antibiotics

  • (neutrophil count less than 1.06×109/litre)

Is hair loss common with chemotherapy?

Yes, alopecia is common

No pharmacological methods of preventing this are available.

How does chemotherapy affect clot risk?

• Chemotherapy increases risk of thromboembolism

Urothelial Toxicity (Definition) – What is urothelial toxicity?

Haemorrhage or damage in the urinary tract

Which drugs commonly cause urothelial toxicity?

• Cyclophosphamide

• Ifosfamide

• oxazaphosphorines

What is used to prevent or treat urothelial toxicity?

Mesna

What precautions should be taken regarding pregnancy?

• Most cytotoxic drugs are teratogenic

• Exclude pregnancy before treatment

• Use contraception during and after therapy

Which drugs may cause permanent male sterility?

• Alkylating agents

• Procarbazine

Reproductive Toxicity (Fertility Preservation) – What should be considered before treatment?

Sperm storage

Reproductive Toxicity (Women) – How can chemotherapy affect women?

May cause premature menopause

What are the three types of CINV?

• Acute (within 24 hrs)

• Delayed (after 24 hrs)

• Anticipatory (before treatment)

Chemotherapy-Induced Nausea & Vomiting (Risk Factors) – Who is at greater risk?

• Women

• Patients under 50

• Anxiety

• who experience motion sickness

• Repeated chemotherapy exposure

CINV (Low Risk Drugs) – Which drugs have low emetic risk?

• Fluorouracil

• Etoposide

• Methotrexate

• Vinca alkaloids

• Abdominal therapy

CINV (Moderate Risk Drugs) – Which drugs have moderate emetic risk?

• Taxanes

• Doxorubicin

• Low-dose cyclophosphamide

• Mitoxantrone

• High-dose methotrexate

CINV (High Risk Drugs) – Which drugs have high emetic risk?

• Cisplatin

• Dacarbazine

• High-dose cyclophosphamide

CINV (Acute Prevention) – How are acute symptoms prevented?

Pretreatment

Low risk:

• Dexamethasone or lorazepam

High risk:

• Ondansetron + dexamethasone + aprepitant

CINV (Delayed Prevention) – How are delayed symptoms prevented?

Moderately emetogenic drugs:

• Dexamethasone + ondansetron

Highly emetogenic drugs:

• Dexamethasone + aprepitant

CINV (Anticipatory Prevention) – What is used for anticipatory nausea and vomiting?

Lorazepam (fast-acting benzodiazepine)

Alkylating Agents: Cyclophosphamide, Isfosfamide, Melphalan main side effects

• Urothelial toxicity

• Increases risk of permanent male sterility

Platinum Compounds (Toxicities) – What are major toxicities?

• Ototoxicity → more common at high does

• Neuropathies(may be irreversible)

Antimetabolites: Cytarabine, Fluorouracil, Methotrexate, Mercaptopurine main side effects

Mucositis and myelosuppression

Anthracyclines (Cardiotoxicity) – What major toxicity occurs at high doses?

• Cardiomyopathy

• Heart failure

• Cardiotoxicity

MHRA Warnings Anthracyclines: Danorubicin, Doxorubicin, Epirubicin, Idraubicin

Maintain formulations (conventional, liposomal, pegylated liposomal) → different BA

Anthracyclines (Harmless Effect) – What harmless effect can occur?

Red/orange urine ("rubi-red urine")

Cytotoxic Antibiotics – What lung toxicity can occur with bleomycin?

• Interstitial pneumonitis

• Pulmonary fibrosis

• Pulmonary toxicity → most common in age 70+

• Vascular toxicity which can lead to myocardial infarctions

Taxanes: Cabazitaxel, Docetaxel, Paclitaxel main side effects

• Premedicate with corticosteroids to reduce retention and hypersensitivity events

• Skin erythema in palms of hands and soles of feet

• Cardiac and respiratory toxicity

Why must vinca alkaloids never be given intrathecally?

Intrathecal administration is fatal

IV ONLY

Vinca Alkaloids (Neurotoxicity) – What neurological adverse effects can occur?

• Paraesthesia

• Peripheral neuropathy

• Headache

• Dizziness

• Acute shortness of breath and bronchospasm

What are important risks of aromatase inhibitors?

• Osteoporosis

• Tendon damage

What are important risks of tamoxifen?

• Increased risk of VTE

• QT prolongation

• Reduced concentration with fluoxetine/paroxetine