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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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, toptecan) |
> 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. |
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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. |
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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. |
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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. |
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Important interactions |
> Reduce doses of mercaptopurine and azathioprine when given with allopurinol. |
> Procarbazine interacts with alcohol. |
> Capecitabine may potentiate warfarin. |
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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. |
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