Cytotoxic Drugs

Question 1

Anthracyclines and other cytotoxic antibiotics

Answer 1

• Doxorubicin
• Epirubicin
• Idarubicin
• Mitoxantrone
• Bleomycin
• Mitomycin

Question 2

Vinca alkaloids

Answer 2

Vinblastine
Vincrisine
Vindesine
Vinorelbine

Question 3

Antimetabolites

Answer 3

Azathioprine

Question 4

Alkylating drugs

Answer 4

Cyclophosphamide Itosfamide
Mephalan
Lomustine
Camustine
Estramustine
Mitobronitol

Question 5

Cytotoxic drugs

Answer 5

• have both anti cancer activity and potential to damage normal tissue
• given to prolong life, to cure or alleviate symptoms
• Cause side effects so need a balance between benefit and risk
• Side effects of cytotoxic drugs occur days or weeks after administration. Be aware of symptoms
• Most cytotoxic drugs are teratogenic and should not be administered during pregnancy, especially during the first trimester
• exclude pregnancy before treatment

Question 6

Neoadjuvant therapy

Answer 6

• chemotherapy and radio therapy OR chemotherapy and surgery OR chemotherapy and surgery and radiotherapy
• initial chemotherapy is aimed at shrinking the primary tumour, thereby rendering local therapy less destructive or more effective

Question 7

Adjuvant therapy

Answer 7

Chemotherapy and Radiotherapy OR Chemotherapy and surgery OR chemotherapy and surgery and radiotherapy
- to prevent cancer after neoadjuvant treatment

Question 8

Guidelines for handling cytotoxic drugs:

Answer 8

1) Trained personnel should reconstitute cytotoxics
2) Reconstitution should be carried out in designated pharmacy areas
3)Protective clothing(including gloves, gowns and mask) should be worn
4) the eyes should be protected and means of first aid specified
5) pregnant staff should avoid exposure to cytotoxic drugs(all females of child bearing age should be informed of reproductive hazards)
6) Use local procedures for dealing with spillages and safe disposal of waste material, including syringes,container and absorbent material
7) staff exposure to cytotoxic should be monitored

Question 9

Safe systems for cytotoxic medicines

Answer 9

Safe systems -
- Cytotoxic drugs for the treatment of cancer should be given as part of a wider pathway of care coordinated by a multidisciplinary team

• Cytotoxic drugs should be prescribed, dispensed and administered only in the context of a written protocol or treatment plan
• injectable cytotoxic drugs should only be dispensed if they are prepared for administration
• oral cytotoxic medicines should only be dispensed with clear direction of use

Question 10

Cytotoxic drugs important safety information

Answer 10

Risk of incorrect dosing of oral anti cancer medication:
- non specialist who prescribes or administers on-going oral cytotoxics should have access to written protocols and treatment plans including guidance on monitoring and treatment of toxicity

• staff dispensing oral cytotoxic meds should confirm that the prescribed dose is appropriate for the patient
• patients should have written information that includes details of the intended oral anti cancer regimens, the treatment plans, arrangements for monitoring taken from original protocol from the hospital
• Staff dispensing oral cytotoxic meds also have access to this information and to advice from an experienced cancer pharmacist in the initiating hospital

Question 11

Extravasation of intravenous drugs

Answer 11

Severe local tissue necrosis if leakage into extravascular compartment occurs, reduce risk by using trained staff

Question 12

Oral Musositis

Answer 12

Sore throat common chemotherapy complication - associated with flurouracil, anthacyclines and methotrexate - FLAME. Prevent with good oral hygiene ( rinse and brush frequently) and use saline,mouth wash. For flurouracil sucking on ice chips during short infusions may be useful

Question 13

Tumour lysis

Answer 13

Rapid destruction of malignant cells. Pre existing hyperuricaemia,dehydration and renal impairment are predisposing factors.Features such as hyperkalaemia,hyperuricaemia,hypocalcaemia, hyperphosphataemia,renal damage and arrhythmias can follow

Question 14

Hyperuricaemia

Answer 14

Present in leukaemia and high grade lymphoma can be worsened by chemotherapy associated with acute renal failure.Treat patients with allopurinol 24hrs before treating tumours. Other drugs can be given - febuxostat or rasburicase

Question 15

Bone marrow suppression with cytotoxics

Answer 15

• all cytotoxics except vincristine and bleomycin cause bone marrow suppression
• check blood count before treatment
• treat any infection before starting cytotoxic drugs
• treat fever with antibiotics
• advise patient to see doctor promptly if having signs of infection
• blood transfusion for anaemia

Question 16

Alopecia

Answer 16

Reversible hair loss is very common

Question 17

Pregnancy and reproductive function

Answer 17

• most cytotoxics are teratogenic
• avoid especially in 1st trimester
• exclude pregnancy before treating with cytotoxic drugs
• provide contraceptive advice before chemo begins

Question 18

Cytotoxic induced nausea and vomiting

Answer 18

• nausea and vomitting causes a lot of distress in patients receiving chemo. May lead to refusal of further treatment, Prophylaxis for nausea and vomiting is very important
• symptoms may be acute - so occurring 24hrs of treatment, delayed - first occurring more than 24hrs after treating or anticipatory - occurring prior to subsequent doses
• delayed and anticipatory symptoms are difficult to control than acute and require different management

Question 19

Patients who are more susceptible to drug induced nausea and vomiting

Answer 19

• susceptibility varies between patients, following patients are more susceptible:
• women
• patients under 50
• anxious patients
• patients experiencing motion sickness
• with repeated exposure to cytotoxic drugs

Question 20

Mildly Emetogenic

Answer 20

• Flurouracil
• Methotrexate
• Etoposide
• Vinca alkaloids
• Abdominal radiotherapy

Question 21

Moderately emetogenic

Answer 21

Taxanes - doxitaxel and paclitaxel
Doxorubicin
Intermediate and low doses of cyclophsphamides
High doses of methotrexate, mitoxantrone

Question 22

Highly emetogenic

Answer 22

Cisplatin
High doses of cyclophosphamide
Dacarbazine

Question 24

Prevention of nausea and vomitting

Answer 24

• acute symptoms: patients at low risk of emesis (dexamethasone or lorazepam) patients at high risk (5 HT3 receptor antagonists) in combination with dexamethasone and aprepitant (neurokinin receptor antagonists)
• delayed symptom: moderately emetogenic chemotherapy, use dexamethasone +5HT3 antagonists. For highly emetogenic chemotherapy, use (dexamethasone+ aprepitant), metoclopramide and rolapitant also licenses
• anticipatory - lorazepam

Question 25

Treatment of cytotoxic induced side effects - Anthracylines

Answer 25

- cardiotoxicity: dose related, potentially life threatening cardiotoxicity Extravasion- follow local management guidelines - speaclisgt advice sought Chemo induced mucositis and myelosupression: - colonic acid used to counter effect of methotrexate, speeds up recovery of methotrexate induced mucositis or myelosupression - folinic acid used in methotrexate overdose - urothelial toxicity:haemorrhagic cystitis (form or urothelial toxicity) caused by cyclophosphamide is treated with Mensa

Question 26

Anthracyclines and other cytotoxic antibiotics

Answer 26

- many cytotoxic antibiotics act as radiomimetics - avoid simultaneous radiotherapy may increase toxicity - important side effects: red urine and cardiotoxicity - mitoxantrone - is an Anthracyclines derivative

Question 27

Doxorubicin - important side effects

Answer 27

Extravastions - can cause tissue necrosis Cardiomyopathy- higher cumulative doses are associated with cardiomyopathy and it is usual to limit cumulative doses to 450mg/m2 Liposomal formulations - may reduce cardiotoxicity and local necrosis Hand - foot syndrome: painful reddening skin eruptions occurs commonly with liposomal formulations treated by cooling hands and feet and avoiding socks,gloves or tight footwear

Question 28

Alkylating agents

Answer 28

Among the ost widely used drugs in cancer chemo They act by damaging DNA,this interfering with cell replication Examples - cyclophosphamides, ifosfamide,mephalan, lomustine

Question 29

Methotrexate

Answer 29

Inhibits dihydrofolate reductase essential for the synthesis of purines and pyriimidines Important safety advice: - should be taken OW - in autoimmune condition and less commonly in some cancer therapy regimens -

Question 30

Methotrexate - report immediately

Answer 30

- onset of blood disorder - sore throat,bruising,mouth ulcers - liver toxicity - nausea and vomitting,abdominal pain,dark urine - respiratory effects = sob - seek immediate medical attention if overdose is suspected

Question 31

Methotrexate caution

Answer 31

Blood count - factors which increase bone marrow suppression (age,renal impairment, concomitant use with another antifolate eg.trimethorprim) Gi toxicity - withdrawal treatment if stomatitis - inflamed sore mouth or diarrhoea develops. May be first sign gastro intestinal toxicity Liver toxicity - do not start treatment or discontinue if an abnormal liver function test results Pulmonary toxicity - advice with dysponea, cough or fever

Question 32

Methotrexate monitoring

Answer 32

- FBC,renal ,liver function every 1-2 weeks stabilised then every 2-3 months - advice patients to report all signs of infections especially sore throat - treatment with follinic acid used - as calcium follinate - may be required in acute toxicity - follinic acid helps to prevent methotrexate induced muctositis and myelosupression

Question 33

Methotrexate patient and carers

Answer 33

- report signs of blood disorders - signs of liver toxicity - respiratory effects - avoid self medication with OTS aspirin or NSAIDS - Issue methotrexate booklets

Question 34

Methotrexate interactions

Answer 34

1) NSAIDS- Increase risk of toxicity 2) Penicllins - Increase risk of methotrexate toxicity 3)Aspirin - increases risk of toxicity 4)PPI - decreased methotrexate clearance 5)statins - increase risk of hepatoxicity 6) most antibiotics - increase risk of hepatoxicity 7)Trimethoprim - increases risk of adverse effects with methotrexate