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More than 50 cytotoxic drugs are used in the management of malignant disease, and the recommended doses and schedules vary
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according to the tumour type and regimen. Anticancer cytotoxic treatment should always be prescribed under the supervision of
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an oncology specialist, and recommendations for use are beyond the scope of this document. Specialists prescribing cytotoxic
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treatment should refer to the relevant East Lancashire treatment protocols, which contain details of prescribing issues,
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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
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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
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appropriate equipment. The administration of cytotoxic drugs by all routes other than the oral route should be undertaken only
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by staff with appropriate training in administration and safe handling, within a designated hospital area which is equipped to deal
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with drug reactions and emergencies. Extravasation of vesicant cytotoxic drugs may cause severe, permanent tissue damage and
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functional loss. To avoid extravasation, designated oncology staff are specially trained in the intravenous administration of
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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,
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relatives and staff. Protective gloves must be worn when handling cytotoxic agents, and staff, patients and relatives must be
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advised on the safe handling and disposal of drugs and excreta. Most drugs are teratogenic, and particular care must be taken to
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avoid the exposure of pregnant women to cytotoxic drugs or contaminated excreta. Men and women receiving chemotherapy
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should avoid conception during treatment.
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Cytotoxic drugs are also used for their immunosuppressive or anti-proliferative effects in the treatment of auto-immune
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conditions, rheumatoid arthritis, psoriasis, or prevention of transplant rejection.
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Prescribing notes
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Common side-effects of cytotoxic drugs include fatigue, reversible alopecia, nausea and vomiting, oral ulceration, diarrhoea,
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skin rashes, bone marrow suppression and effects on fertility. Possible effects on fertility and gonadal function must be
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discussed before treatment begins.
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Bone marrow suppression
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| > 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
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| > 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
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| > 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
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| > 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
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| > 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
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| > 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
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| > 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
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| > 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
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| > 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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