Cytotoxic Drugs and Side Effects

Considerations for the drug handling of cytotoxic drugs.

• Harmful through skin contact, inhalation and ingestion

• Risk of nausea, organ damage, skin reactions, reproductive effects

• Women of child bearing age should avoid handling these drugs

• Should be handled in enclosed systems with ventilations

• PPE and eye protection should be worn

• Safe waste disposal and spillage handling

Name the alkylating agents and risks associated with treatment.

• Cyclophosphamide

• Ifosfamide

• Melphalan

Risk of urothelial toxicity and permanent male sterility.

Name the platinum compounds and risks associated with treatment.

• Carboplatin

• Cisplatin

• Oxaliplatin

Risk of ototoxicity and irreversible neuropathies.

Name the antimetabolites and risks associated with treatment.

• Cytarabine

• Fluroracil

• Methotrexate

• Mercaptopurine

Risks of mucositis and myelosuppression.

Name the anthracyclines and risks / MHRA warning associated with treatment.

Urine colour?

• Daunorubicin

• Doxorubicin

• Epirubicin

• Idarubicin

MHRA: maintain formulations i.e. conventional, liposomal, pegylated liposomal.

High doses lead to cardiomyopathy, heart failure and cardiotoxicity.

• Reduced cardiotoxicity with liposomal formulations but can cause macular skin eruptions - prevented by cooling hands/feet, avoid gloves socks.

Risks of oral mucositis.

Rubi = red urine

Name the cytotoxic antibiotics and risks associated with treatment.

• Bleomycin

• Mitomycin

Risk of pulmonary dysfunction, most commonly interstitial pneumonitis which leads to pulmonary fibrosis. - most common in 70+

Risk of vascular toxicity which can lead to MIs.

Name the taxanes and risks associated with treatment.

• Cabazitaxel

• Docetaxel

• Paclitaxel

Risks of fluid retention and hypersensitivity events - premedicate with corticosteroids.

Risk of skin erythema in palms of hands and soles of feet.

Risk of cardiac and respiratory toxicity.

Name the vinca alkaloids and risks associated with treatment.

• Vinblastine

• Vincristine

• Vindesine

Risk of neurotoxicity - paraesthesia, peripheral neuropathy, headaches, dizziness.

Risks of SOB and bronchospasms.

Name the aromatase inhibitors and risks associated with treatment.

• Anastrazole

• Exemestane

• Letrozole

Increased risk of osteoporosis and tendon damage.

Risks associated with tamoxifen treatment.

What drugs interact with tamoxifen.

Increased risk of VTE and QT prolongation.

Tamoxifen concentration reduced by fluoxetine and paroxetine.

What is neoadjuvant chemotherapy?

Chemotherapy given before surgery/radiotherapy to shrink the tumour.

What is adjuvant chemotherapy?

Chemotherapy given after definitive treatment to reduce risk of metastatic disease.

Why is extravasation dangerous with some cytotoxic drugs?

Can cause severe tissue necrosis.

Should only be administered by appropriately trained staff.

Which cytotoxic drugs commonly cause oral mucositis?

Fluorouracil, methotrexate, anthracyclines (-rubicins)

How to prevent oral mucositis?

What is the treatment?

• Good oral hygiene

• Frequent mouth rinsing

• Sucking ice chips with fluorouracil

Treatment (saline mouthwash) is less effective than preventing.

If caused by methotrexate, use folinic acid (levofolinic acid).

• also give folinic acid if myelosuppression occurs

What are the key biochemical features of tumour lysis syndrome?

Caused by rapid destruction of malignant cells, particularly in blood cancers (lymphomas, leukaemias, myelomas) which can cause renal failure and arrhythmias.

• Hyperkalaemia

• Hyperuricaemia

• Hyperphosphataemia

• Hypocalcaemia

How is hyperuricaemia prevented in high-grade lymphoma/leukaemia?

Allopurinol 24h before chemo + hydration.

What drug interaction must be considered with allopurinol?

Reduce dose of mercaptopurine/azathioprine.

What is an alternative to allopurinol for hyperuricaemia prophylaxis?

Febuxostat (start 2 days before therapy).

What drug rapidly lowers uric acid in haematological malignancy (and used for TLS)?

Rasburicase

Which cytotoxic drugs do NOT typically cause bone marrow suppression?

Vincristine and bleomycin.

All other drugs have a risk of bone marrow suppression which occurs 7-10 days after administration.

What may be needed after varicella exposure in non-immune patients?

Antiviral / immunoglobulin prophylaxis.

Does chemotherapy increase thromboembolism risk?

Yes, chemotherapy increases VTE risk.

What is the pregnancy risk with cytotoxic drugs, which trimester is highest risk?

Most are teratogenic, especially in 1st trimester.

Exclude pregnancy before cytotoxic therapy.

Use effective contraception during and after treatment.

Which chemotherapy agents have an increased risk of permanent male sterility?

Alkylating drugs (cyclophosphamide, ifosfamide, melphalan) or procarbazine.

Consider sperm storage.

Affects women less however can cause premature menopause.

What are the three types of chemotherapy-induced nausea/vomiting?

Acute, delayed and anticipatory.

Delayed and anticipatory are more difficult to treat/control.

More common in women, patients < 50 years, anxiety and repeated exposure.

Name the mildly emetogenic cytotoxics.

What is used to prevent emesis?

• Fluorouracil

• Etoposide

• Low-dose methotrexate

• Vinca alkaloids

Pretreatment with dexamethasone or lorazepam

Name the moderately emetogenic cytotoxics.

What is used to prevent emesis and for delayed symptoms?

• Taxanes

• Doxorubicin

• Cyclophosphamide (low/intermediate doses)

• Mitoxantrone

• High-dose methotrexate

Pretreatment with dexamethasone or lorazepam or 5HT₃-receptor antagonist (-setrons) for delayed symptoms.

• Rolapitant and metoclopramide hydrochloride are also licensed for delayed chemotherapy-induced N&V.

Name the highly emetogenic cytotoxics.

• Cisplatin

• Dacarbazine

• High-dose cyclophosphamide

What is standard prophylaxis for high emesis risk chemotherapy?

5HT3 antagonist (-setrons) + dexamethasone + aprepitant (neurokinin receptor antagonist)

What can help with anticipatory nausea?

Lorazepam for the stress and anxiety.

What drug prevents haemorrhagic cystitis with ifosfamide or cyclophosphamide?

Mesna (binds acrolein)

What is the key lethal administration error with vinca alkaloids? MHRA / never event.

Intrathecal administration can be fatal.

Should only be given intravenously.

How is endocrine therapy used in the treatment of breast cancer?

What type of breast cancer is it used in?

Used as neoadjuvant drug therapy (drug treatment before surgery) to reduce the size of the tumour.

Only used in oestrogen receptor (ER) positive breast cancer

In postmenopausal women with a medium to high risk of breast cancer recurrence, what type of adjuvant endocrine therapy used?

1. First line: aromatase inhibitor - letrozole, anastrozole

2. Second line if the above is not tolerated or contraindicated: tamoxifen

In postmenopausal women with a low risk of breast cancer recurrence, what type of adjuvant endocrine therapy used?

Tamoxifen

In premenopausal women or men with a low risk of breast cancer recurrence, what type of adjuvant endocrine therapy used?

First line: tamoxifen

Second line: aromatase inhibitor - letrozole, anastrozole

What is the duration for endocrine therapy in breast cancer?

5 years, can be extended in those taking tamoxifen for up to 10 years.