More than 50 cytotoxic drugs are used in the management of malignant disease, and the recommended doses and schedules vary according to the tumour type and regimen. Anticancer cytotoxic treatment should always be prescribed under the supervision of an oncology specialist, and recommendations for use are beyond the scope of this document. Specialists prescribing cytotoxic treatment should refer to the relevant East Lancashire treatment protocols, which contain details of prescribing issues, management of toxic effects and supportive care.

When oral cytotoxic drugs are used for the treatment of malignant disease, the whole course will be dispensed by the hospital pharmacy. The prescription should not be repeated except on the explicit instruction of a specialist.

Parenteral cytotoxic drugs should be reconstituted and dispensed by trained oncology pharmacy staff who have access to appropriate equipment. The administration of cytotoxic drugs by all routes other than the oral route should be undertaken only by staff with appropriate training in administration and safe handling, within a designated hospital area which is equipped to deal with drug reactions and emergencies. Extravasation of vesicant cytotoxic drugs may cause severe, permanent tissue damage and functional loss. To avoid extravasation, designated oncology staff are specially trained in the intravenous administration of vesicant drugs. Extravasation is a medical emergency, and expert advice and treatment must be obtained immediately.

In addition to their anti-tumour effects, cytotoxic drugs may damage normal tissues and are a potential hazard to patients, relatives and staff. Protective gloves must be worn when handling cytotoxic agents, and staff, patients and relatives must be advised on the safe handling and disposal of drugs and excreta. Most drugs are teratogenic, and particular care must be taken to avoid the exposure of pregnant women to cytotoxic drugs or contaminated excreta. Men and women receiving chemotherapy should avoid conception during treatment.

Cytotoxic drugs are also used for their immunosuppressive or anti-proliferative effects in the treatment of auto-immune conditions, rheumatoid arthritis, psoriasis, or prevention of transplant rejection.

Prescribing notes                                                                                                                                                                         Common side-effects of cytotoxic drugs include fatigue, reversible alopecia, nausea and vomiting, oral ulceration, diarrhoea, skin rashes, bone marrow suppression and effects on fertility. Possible effects on fertility and gonadal function must be discussed before treatment begins.

Bone marrow suppression

• Most cytotoxic drugs cause myelosuppression, and treatment must not be given until the full blood count has been checked.
  
• Fever in a patient who may be neutropenic (absolute neutrophil count less than 1x109/L) requires immediate treatment with intravenous broad-spectrum antibiotics. Specialist advice must be obtained at once as neutropenic sepsis may be fatal if not treated promptly. For patients receiving cisplatin chemotherapy the neutropenic sepsis protocol using meropenem should be used.  (Rather than a combination with an aminoglycosides (e.g. gentamicin) as these can also cause nephrotoxicity.)
  
• Thrombocytopenia occurs less commonly. Platelet transfusions may be required if the platelet count is below 12x109/L, or between 12x109/L and 50x109/L with associated mucosal bleeding.
  

Nausea and vomiting

• Many cytotoxic drugs cause emesis. Cisplatin, cyclophosphamide, dacarbazine, ifosfamide and doxorubicin may cause severe emesis which persists for several days.
  
• Premedication with dexamethasone and ondansetron is recommended to prevent acute emesis.
  
• Delayed emesis may be prevented by dexamethasone given with metoclopramide or domperidone.
  
• Vomiting in patients unable to take oral medication may be helped by inttramuscular metoclopramide, prochlorperazine or cyclizine.

Vesicant drugs  

• The following drugs are vesicant: amsacrine, dactinomycin (actinomycin D), daunorubicin, doxorubicin, epirubicin, idarubicin, mitomycin, vincristine, vinblastine, vinorelbine, vindesine. Administer by slow intravenous bolus into fast-running drip or into central line to avoid extravasation.

Hypersensitivity/allergy  

• Crisantaspase, rituximab, trastuzumab and the taxanes (pacliaxel and docetaxel) may cause severe anaphylaxis and should only be administered where resuscitation facilities are available.
  
• Taxanes may cause a sub acute hypersensitivity syndrome with fluid retention, fever and rash.
  
• Procarbazine and chlorambucil may cause severe rash, precluding further treatment.

Gastro-intestinal toxicity 

• Fluorouracil/folinic acid, doxorubicin, capecitabine and raltitrexed may cause severe stomatitis and diarrhoea
  
• The course of capecitabine should be discontinued in the vent of oral ulceration or moderately severe diarrhoea, and specialist advice obtained.
  
• Severe diarrhoea may occur after topoisomerase 1 inhibitors ( irinotecan,
  
• Severe diarrhoea may require hospital admission for intravenous hydration.
  
• Patients receiving irinotecan are given a discharge prescription for ciprofloxacin and loperamide to be taken if diarrhoea persists after 24 hours.

Neurotoxicity

• Bortezomib, cisplatin, taxanes, vinca drugs and altretamine may cause neurotoxicity, usually manifest as peripheral sensory neuropathies, autonomic neuropathies or ototoxicity. Commonest symptoms are constipation, paraesthesiae and tinnitus, and these may warrant dose reduction.
  
• Ifosfamide may cause encephalopathy in renal dysfunction.

Renal/urothelial toxicity

• Cisplatin causes tubular dysfunction unless it is administered with adequate prehydration.
  
• Cyclophosphamide and ifosfamide cause urothelial toxicity and haemorrhagic cystitis. Increase oral fluid intake for 48 hours, and give prophylactic mesna with ifosfamide, and with cyclophosphamide if necessary.
  
• Anthracyclines may cause red or blue/green discolouration of the urine.

Cardiac toxicity

• Congestive cardiomyopathy may occur after large cumulative doses of anthracyclines.
  
• Fluorouracil may cause coronary spasm mimicking angina.
  
• Concomitant use of anthracyclines with trastuzumab is associated with cardiotoxicity. The use of anthracyclines even after stopping trastuzumab may carry a higher risk of cardiotoxicity and if possible should be avoided for up to 22 weeks. If anthracyclines need to be used, cardiac function should be monitored.
  
• Rituximab should be used with caution in patients receiving cardiotoxic chemotherapy or with a history of cardiovascular disease because exacerbation of angina, arrhythmia, and heart failure have been reported.

Important interactions

• Reduce doses of mercaptopurine and azathioprine when given with allopurinol.
  
• Procarbazine interacts with alcohol.
  
• Capecitabine may potentiate warfarin.

Cutaneous reactions 

• The course of capecitabine should be discontinued in the event of painful hands and soles of feet interfering with function, and specialist advice obtained.

8.1 Cytotoxic drugs

8.3.1 Oestrogens

8.3.2 Progestogens

8.3.4 Hormone antagonists

8.3.4.1 Breast Cancer

8.3.4.2 Gonadorelin analogues and gonadotrophin-releasing hormone antagonists

Metastatic cancer of the prostate usually responds to hormone treatments aimed at androgen depletion. 

Gonadorelin analogues:-

Goserelin and leuprorelin are recommended for use within their licensed indications, with goserelin recommended as the first line product. Any unlicensed uses (e.g. precocious puberty) should not be transferred to primary care prescribers –prescribing should be retained by secondary care.  There are two shared care protocols in place for the use of goserelin (the preferred LHRH analogue).  One covers the use in gynaecology, the other covers the use in oncology settings (breast & prostate cancer), and they can be accessed online - click here to access them .

First Line 

AMBER with SHARED CARE     Goserelin injection 3.6mg, 10.8mg      

Second Line                                                

AMBER with SHARED CARE     Leuprorelin injection 3.75mg, 11.25mg

(currently no shared care protocols exist for the use of leuprorelin locally as it is a second line agent)

Anti-androgens:-

Gonadotrophin-releasing hormone antagonists

Degarelix is a gonadotrphin-releasing hormone antagonist used to treat advanced hormone dependent prostate cancer which does not induce a testosterone surge or tumour 'flare'. Anti-androgen therapy is not required when Degarelix is used.                                                                                                                                                                                     CAMET recommends its use ONLY where LHRH analogues or concomittant anti-androgens are contra-indicated.

Degarelix is recommended as an option for treating advanced hormone-dependent prostate cancer in people with spinal metastases NICE TA404 

AMBER    Degarelix injection with diluent 80mg and 120mg          

Click here to access a Prescribing Information Sheet for Degarelix (Firmagon®)                            

8.3.4.3 Somatostatin analogues

Octreotide may be used in line with its licensed indications.  (NB - Any off license prescribing should not be passed on to primary care prescribers).

Lanreotide may be prescribed in line with its licensed indications only following recommendation from a specialist centre. (NB - Any off license prescribing should not be passed on to primary care prescribers)