Cytotoxics

Question 1

Cytotoxic drugs have

Answer 1

Cytotoxic drugs have anti-cancer activity, but they also damage normal tissue, most are teratogenic.
- They are often used with radiotherapy and surgery

Question 2

Cytotoxic Drug handling guidelines

Answer 2

• Only trained personnel should reconstitute cytotoxic drugs in a designated pharmacy area.
• Gloves, gowns and masks should be worn, and the eyes protected.
• Pregnant staff should avoid exposure to cytotoxic drugs and all staff exposure should be monitored.

Question 3

Cytotoxic drug doses

Answer 3

 Combination regimens are common since they may be more effective and reduce the risk of drug resistance, but they are normally more toxic than monotherapy.
 Cytotoxic doses are determined based on the body surface area, weight, neutrophil count, renal and hepatic function and previous response to the drug.

Question 4

Side effects of cytotoxic drugs

Answer 4

Cytotoxic drugs share many side-effects, they may occur days or weeks after therapy:

1. Oral mucositis (sore mouth)
2. Nausea and vomiting
3. Bone-marrow suppression
4. Alopecia (hair loss)
5. severe local tissue necrosis
6. Tumour lysis syndrome
7. Hyperuricaemia
8. Chemotherapy increases the risk of venous thromboembolism.
9. Most cytotoxic drugs are teratogenic. Exclude pregnanacy before treatment.
10. Urothelial toxicity,
11. Extravasation risk with IV drugs

Question 5

SE: Oral mucositis

Answer 5

(sore mouth) is a common complication. The best treatment is prevention (i.e. good oral hygiene, rinse mouth frequently, use a soft toothbrush 2-3 times daily). For fluorouracil, sucking ice cubes during short infusions of the drug is also helpful.

Question 6

SE: Nausea and vomiting

Answer 6

are common during treatment and can lead to refusal of treatment. The prevention of acute N+V involves dexamethasone and lorazepam, in severe cases… ondansetron or aprepitant can be used. To prevent delated N+V is much the same: metoclopramide can also be used. Lorazepam can be used to prevent anticipatory N+V.

Question 7

SE: Bone-marrow suppression

Answer 7

is a common side-effect of all cytotoxic drugs (except vincristine + bleomycin). Commonly occurs 7-10 days after administration, but is delayed for certain drugs, such as carmustine, lomustine + melphalan. Peripheral blood counts should be taken before each treatment + reduce dose if not fully recovered from previous dose. Cytotoxic drugs may be CI in patients with acute infection. If fever presents in a neutropenic patient, treat immediately with broad-spectrum abx, in selected patient’s granulocyte stimulants can be used to reduce severity + duration of neutropenia. Symptomatic anaemia is usually treated with red blood cell transfusions.

Question 8

Mildly emetogenic treatment

Answer 8

fluorouracil, etoposide, methotrexate (less than 100 mg/m2, low dose in children), the vinca alkaloids + abdominal radiotherapy.

Question 9

Moderately emetogenic treatment

Answer 9

taxanes, doxorubicin hydrochloride, intermediate + low doses of cyclophosphamide, mitoxantrone, + high doses of MTX (0.1– 1.2 g/m2).

Question 10

Highly emetogenic treatment

Answer 10

cisplatin, dacarbazine, and high doses of cyclophosphamide.

Question 11

SE: Alopecia (hair loss)

Answer 11

is a common side-effect. It is unpreventable, but reversible. No pharmacological methods of preventing this are available.

Question 12

SE: severe local tissue necrosis

Answer 12

A number of cytotoxic drugs will cause severe local tissue necrosis if leakage into the extravascular compartment occurs. To reduce risk of extravasation injury, cytotoxic drugs should be administered by appropriately trained staff.

Question 13

SE: Tumour lysis syndrome

Answer 13

occurs due to rapid destruction of malignant cells (due to the drug or spontaneously). Features include hyperkalaemia, hyperuricaemia and hyperphosphataemia with hypocalcaemia. Renal damage and arrythmias can follow.

Question 14

SE: Hyperuricaemia,

Answer 14

which may be present in high-grade lymphoma and leukaemia, can be worsened by chemotherapy and is associated with acute renal failure. Allopurinol should be started 24 hours before treating such tumours and patients should be adequately hydrated. The dose of mercaptopurine or azathioprine should be reduced if allopurinol is given. Febuxostat may also be used and should be started 2 days before cytotoxic therapy is initiated. Rasburicase can also be used (rapidly reduces plasma uric acid concentration).

Question 15

SE: VTE

Answer 15

Chemotherapy increases the risk of venous thromboembolism. Cancer is a significant risk factor. VTE more common with tamoxifen and thalidomide/linadamide

Question 16

SE: Pregnancy

Answer 16

most cytotoxic drugs are teratogenic. Exclude pregnanacy before treatment. Offer contraceptive advice to men and women. Alkylating drugs + procarbazine cause permanent infertility (counsel male patient on sperm storage and women on early menopause occurring)

Question 17

SE: Urothelial toxicity,

Answer 17

haemorrhagic cystitis is a common manifestation of urothelial toxicity which occurs with the oxazaphosphorines, cyclophosphamide and ifosfamide. Treat with Mesna.

Question 18

SE: Extravasation risk with IV drugs,

Answer 18

causing severe local tissue necrosis.

Question 19

Cytotoxic drug classes

Answer 19

• Anthracyclines ‘rubicin’
• Antineoplastic antibiotics
• Vinca alkaloids
• Antimetabolites
• Alkylating drugs
• Aromatase inhibitors
• Taxanes

Question 20

Anthracyclines ‘rubicin’

Answer 20

o Examples: Doxorubicin, epirubicin, idarubicin, daunorubicin.
o Side effects: Cardiotoxicity (dose related), red urine.
o Liposomal formulations of doxorubicin reduce incidence of cardiotoxicity + extravasation but cause hand + foot syndrome (painful, macular reddening skin eruptions). Can be prevented by cooling hands + feet, avoiding socks, gloves or tight-fitting footwear. Treat with dexrazoxane.

Question 21

Antineoplastic antibiotics

Answer 21

o Examples: Bleomycin
o Side effects: Progressive pulmonary fibrosis (dose-related + may occur at lower doses in elderly. Stop bloemycin if this occurs). Pulmonary toxicity

Question 22

Vinca alkaloids

Answer 22

o Examples: Vinblastine, Vincristine, Vindesine, Vinflunine, Vinorelbine
o Administration: IV ONLY. Intrathecal can cause severe neurotoxicity.
o Side effects: CNS toxicity
o NPSA Alert: Adults + teenage patients treated in an adult or adolescent unit should receive dose in 50ml minibag. Children’s unit receive doses by syringe.

Question 23

Antimetabolites

Answer 23

o Examples: Methotrexate, Fluorouracil, Capecitabine, Mercaptopurine
o Side effects: Oral mucositis, myelosuppression
o Folinic acid speeds up recover in MTX side effects + overdose

Question 24

Alkylating drugs

Answer 24

o Examples: Cyclophosphamide, carmustine, lomustine, melphalan, chlorambucil, ifosfamide
o Side effects: Permeant male sterility (cyclophosphamide), non-lymphocytic leukaemia

Question 25

Aromatase inhibitors

Answer 25

o Examples: Anastrazole, Letrozole - used to treat breast cancer.
o Do NOT give to premenopausal women. Aromatase inhibitors are anti-oestrogens

Question 26

Taxanes

Answer 26

o Examples: Paclitaxel, Docetaxel, Side effects: Cardiac disease, pneumonitis, sepsis

Question 27

Important safety information: risk of incorrect dosing of oral anti-cancer medicines

Answer 27

• Non-specialists who prescribe or administer on-going oral cytotoxic medication should have access to treatment plans, including guidance on the monitoring + treatment of toxicity
• Staff dispensing oral cytotoxic medicines should confirm that the prescribed dose is appropriate. Patients should have written information that includes details of the oral anti-cancer regime, treatment plan and arrangements for monitoring…. Staff dispensing the medicine should also have access to this information.

Question 28

Safe systems for cytotoxic medicines

Answer 28

• Cytotoxic drugs for the treatment of cancer should be given as part of a treatment plan co-ordinated by a multidisciplinary team.
• Cytotoxic drugs should be prescribed, dispensed and administered in accordance of a treatment plan
• Injectable cytotoxic drugs should only be dispensed if they are prepared for administration
• Oral cytotoxic medicines should be dispensed with clear directions for use.