BNF for Children 2011-2012

416 8.1 Cytotoxic drugs BNFC 2011–20128 Malignant disease and immunosuppressionsymptoms vary according to the dose, to other drugsadministered, and to the individual’s susceptibility toemetogenic stimuli.Mildly emetogenic treatment—fluorouracil, etoposide,low doses of methotrexate, the vinca alkaloids, andabdominal radiotherapy.Moderately emetogenic treatment—carboplatin, doxorubicin,intermediate and low doses of cyclophosphamide,mitoxantrone, and high doses of methotrexate.Highly emetogenic treatment—cisplatin, dacarbazine,and high doses of alkylating drugs.Anti-emetic drugs, when given regularly, help prevent orameliorate emesis associated with chemotherapy inchildren.Prevention of acute symptoms For patients at low riskof emesis, pretreatment with metoclopramide (or lesscommonly domperidone) continued for up to 24 hoursafter chemotherapy, is often effective (section 4.6); a5HT 3 -receptor antagonist (section 4.6) may also be ofbenefit.For patients at high risk of emesis or when other treatmentis inadequate, a 5HT 3 -receptor antagonist (section4.6) is often highly effective. The addition of dexamethasoneand other anti-emetics may also be required.Prevention of delayed symptoms Dexamethasone,given by mouth, is the drug of choice for preventingdelayed symptoms; it is used alone or with metoclopramide.The 5HT 3 -receptor antagonists may have arole in preventing uncontrolled symptoms.Prevention of anticipatory symptoms Good symptomcontrol is the best way to prevent anticipatory symptoms.Lorazepam can be helpful for its amnesiac, sedative,and anxiolytic effects.Bone-marrow suppression All cytotoxic drugsexcept vincristine and bleomycin cause bone-marrowdepression. This commonly occurs 7 to 10 days afteradministration, but is delayed for certain drugs, such asmelphalan. Peripheral blood counts must be checkedbefore each treatment. The duration and severity ofneutropenia can be reduced by the use of granulocytecolonystimulating factors (section 9.1.6); their useshould be reserved for children who have previouslyexperienced severe neutropenia.Infection in a child with neutropenia requires immediatebroad-spectrum antibacterial treatment that covers alllikely pathogens (Table 1, section 5.1). Appropriatebacteriological investigations should be conducted assoon as possible. All children should be investigated andtreated under the supervision of an appropriate oncologyor haematology specialist. Antifungal treatment(section 5.2) may be required in a child with prolongedneutropenia or fever lasting longer than 4–5 days.Chickenpox and measles can be particularly hazardousin immunocompromised children. Varicella–zosterimmunoglobulin (section 14.5.2) is indicated if thechild does not have immunity against varicella andhas had close contact with infectious chickenpox orherpes zoster. Antiviral prophylaxis (section 5.3.2.1)can be considered in addition to varicella–zosterimmunoglobulin or as an alternative if varicella–zosterimmunoglobulin is inappropriate. If an immunocompromisedchild has come into close contact with an infectiousindividual with measles, normal immunoglobulin(section 14.5.1) should be given.For advice on the use of live vaccines in individuals withimpaired immune response, see section 14.1.Alopecia Reversible hair loss is a common complication,although it varies in degree between drugs andindividual patients.Pregnancy and reproductive function Most cytotoxicdrugs are teratogenic and should not be administeredduring pregnancy, especially during the first trimester.Considerable caution is necessary if a pregnantwoman presents with cancer requiring chemotherapy,and specialist advice should always be sought.Contraceptive advice should be given to men andwomen before cytotoxic therapy begins (and shouldcover the duration of contraception required after therapyhas ended).Regimens that do not contain an alkylating drug mayhave less effect on fertility, but those with an alkylatingdrug carry the risk of causing permanent male sterility(there is no effect on potency). Pretreatment counsellingand consideration of sperm storage may be appropriate.Women are less severely affected, though the span ofreproductive life may be shortened by the onset of apremature menopause. No increase in fetal abnormalitiesor abortion rate has been recorded in patients whoremain fertile after cytotoxic chemotherapy.Long-term and delayed toxicity Cytotoxic drugsmay produce specific organ-related toxicity in children(e.g. cardiotoxicity with doxorubicin or nephrotoxicitywith cisplatin and ifosfamide). Manifestations of suchtoxicity may not appear for several months or evenyears after cancer treatment. Careful follow-up of survivorsof childhood cancer is therefore vital; national andlocal guidelines have been developed to facilitate this.Thromboembolism Venous thromboembolism canbe a complication of cancer itself, but chemotherapyincreases the risk.Tumour lysis syndrome Tumour lysis syndromeoccurs secondary to spontaneous or treatment relatedrapid destruction of malignant cells. Patients at risk oftumour lysis syndrome include those with non-Hodgkin’slymphoma (especially if high grade and bulkydisease), Burkitt’s lymphoma, acute lymphoblastic leukaemiaand acute myeloid leukaemia (particularly if highwhite blood cell counts or bulky disease), and occasionallythose with solid tumours. Pre-existing hyperuricaemia,dehydration and renal impairment are also predisposingfactors. Features, include hyperkalaemia,hyperuricaemia, and hyperphosphataemia with hypocalcaemia;renal damage and arrhythmias can follow.Early recognition of patients at risk, and initiation ofprophylaxis or therapy for tumour lysis syndrome, isessential.Drugs for cytotoxic-induced sideeffectsAnthracycline-induced cardiotoxicityThe anthracycline cytotoxic drugs are associated withdose-related, cumulative, and potentially life-threateningcardiotoxic side-effects.