, breast-feeding (Appendix 5) ease, hyperbilirubinaemia, jaundice and fibrosis);

(Appendix 4), breast-feeding (Appendix 5) ease, hyperbilirubinaemia, jaundice and fibrosis);

Side-effects see section 8.1 and notes above; also cardiac tamponade in thalassaemia; pneumonia; skin

anorexia; cardiotoxicity at high doses; interstitial

disease

hyperpigmentation pulmonary fibrosis; inappropriate secretion of anti- Dose

diuretic hormone, disturbances of carbohydrate gnant metabolism; urothelial toxicity; pigmentation of . Chronic myeloid leukaemia, induction of remission, by mouth , 60 micrograms/kg daily (max. 4 mg);

palms, nails, and soles

Mali

maintenance, usually 0.5–2 mg daily . Conditioning treatment before haematopoietic stem-

Cyclophosphamide (Non-proprietary) A

8 cell transplantation, by mouth or by intravenous

Tablets , s/c, cyclophosphamide (anhydrous) 50 mg, infusion , consult product literature

net price 20 = £2.49. Label: 27 Injection

, powder for reconstitution, cyclophosph- (Fabre) TA

Busilvex c

amide, net price 500-mg vial = £2.88; 1-g vial = £5.04 Concentrate for intravenous infusion , busulfan

6 mg/mL, net price 10-mL vial = £201.25 Endoxana c (Baxter) A Myleran c (GSK)

Tablets , s/c, cyclophosphamide 50 mg, net price 100- A Tablets , f/c, busulfan 2 mg, net price 25-tab pack =

tab pack = £12.00. Label: 23, 25, 27 £5.20

Injection , powder for reconstitution, cyclophosph- amide. Net price 200-mg vial = £1.86; 500-mg vial =

CARMUSTINE £3.54; 1-g vial = £6.18

Indications see notes above Cautions see section 8.1 and notes above

ESTRAMUSTINE PHOSPHATE

Contra-indications pregnancy (Appendix 4), breast- Indications prostate cancer feeding

Side-effects see section 8.1; hepatic impairment

Cautions

see section 8.1 and notes above; irritant (Appendix 2); renal impairment (Appendix 3) to tissues

Contra-indications peptic ulceration, cardiac disease Gliadel c (Link) A Side-effects see section 8.1; also gynaecomastia,

Implant , carmustine 7.7 mg, net price = £650.38 altered liver function, cardiovascular disorders (angina and rare reports of myocardial infarction)

CHLORAMBUCIL Dose

. 0.14–1.4 g daily in divided doses (usual initial dose Indications see notes above

560 mg daily)

Cautions see section 8.1 and notes above; history of Counselling Each dose should be taken not less than 1 hour epilepsy and children with nephrotic syndrome

before or 2 hours after meals and should not be taken with (increased risk of seizures); hepatic impairment

dairy products

(Appendix 2); avoid in acute porphyria (section 9.8.2) Estracyt c Contra-indications (Pharmacia) A pregnancy (Appendix 4), breast-

Capsules , estramustine phosphate 140 mg (as feeding

disodium salt). Net price 100-cap pack = £171.28. Side-effects see section 8.1 and notes above

Label: 23, counselling, see above

BNF 57

8.1.2 Anthracyclines and other cytotoxic antibiotics 465

IFOSFAMIDE

THIOTEPA

Indications see notes above Indications see notes above and section 7.4.4 Cautions see section 8.1 and notes above; ensure

Cautions see section 8.1; interactions: Appendix 1 satisfactory electrolyte balance and renal function

(thiotepa)

before each course (risk of tubular dysfunction, Fan- Contra-indications pregnancy (Appendix 4); breast- coni’s syndrome or diabetes insipidus if renal toxicity

feeding

not treated promptly); renal impairment (avoid if Side-effects see section 8.1 serum creatinine concentration greater than 120 micromol/litre; Appendix 3); interactions:

Thiotepa (Goldshield) A Appendix 1 (ifosfamide)

Injection , powder for reconstitution, thiotepa, net Contra-indications myelosuppression; urinary-tract

price 15-mg vial = £5.20 obstruction; acute infection (including urinary-tract

infection); urothelial damage; hepatic impairment;

TREOSULFAN

pregnancy (Appendix 4), breast-feeding Indications see notes above Side-effects see section 8.1 and notes above; also

Cautions see section 8.1 drowsiness, confusion, disorientation, restlessness,

Contra-indications pregnancy; breast-feeding psychosis; urothelial toxicity, renal toxicity (see Cau-

tions, above) Side-effects see section 8.1 and notes above

Dose Mitoxana c (Baxter) A . Consult product literature

Injection , powder for reconstitution, ifosfamide. Net price 1-g vial = £27.03; 2-g vial = £45.49 (hosp. only)

Treosulfan (Medac) A Capsules , treosulfan 250 mg. Net price 20 = £77.34 Label: 25

Injection , powder for reconstitution, treosulfan. Net Indications see notes above

LOMUSTINE

price 1 g = £39.44; 5 g = £152.41 (both in infusion Cautions see section 8.1 and notes above

bottle with transfer needle) Contra-indications severe renal impairment; coeliac

disease; pregnancy (Appendix 4); breast-feeding Side-effects see section 8.1 and notes above

8.1.2 Anthracyclines and other

Dose

cytotoxic antibiotics

. Used alone, 120–130 mg/m body-surface every 6–8 weeks

Drugs in this group are widely used. Many cytotoxic Lomustine (Medac) A antibiotics act as radiomimetics and simultaneous use of

Capsules , blue/clear, lomustine 40 mg. Net price 20- radiotherapy should be avoided as it may result in cap pack = £396.19

markedly enhanced toxicity. Note The brand name CCNU

has been used for lomustine Daunorubicin, doxorubicin, epirubicin and ida-

capsules rubicin are anthracycline antibiotics. Mitoxantrone

Malignant

(mitozantrone) is an anthracycline derivative.

Doxorubicin is used to treat the acute leukaemias, Indications see notes above

MELPHALAN

Hodgkin’s and non-Hodgkin’s lymphomas, paediatric malignancies and some solid tumours. It is given by

disease

Cautions see section 8.1 and notes above; renal injection into a fast-running infusion, commonly at 21-

impairment (Appendix 3); interactions: Appendix 1 day intervals. Extravasation can cause severe tissue (melphalan)

necrosis. Doxorubicin is largely excreted in the bile Contra-indications pregnancy (Appendix 4); breast-

and an elevated bilirubin concentration is an indication

and

feeding for reducing the dose. Supraventricular tachycardia Side-effects see section 8.1 and notes above

related to drug administration is an uncommon compli-

immunosupp

Dose cation. Higher cumulative doses are associated with . By mouth , multiple myeloma, dose may vary

cardiomyopathy and it is usual to limit total cumulative according to regimen; typical dose 150 micr-

doses to 450 mg/m because symptomatic and poten- ograms/kg daily for 4 days, repeated every 6 weeks

tially fatal heart failure is common above this dose. Ovarian adenocarcinoma, 200 micrograms/kg daily

Patients with cardiac disease, hypertension, the elderly, and those who have received myocardial irradiation

ressio

for 5 days, repeated every 4–8 weeks Advanced breast cancer, 150 micrograms/kg daily for

should be treated cautiously. Cardiac monitoring may

5 days, repeated every 6 weeks assist in determining safe dosage. Some evidence sug-

Polycythaemia vera, initially, 6–10 mg daily reduced gests that weekly low-dose administration may be less after 5–7 days to 2–4 mg daily until satisfactory

cardiotoxic. Doxorubicin is also given by bladder instil- response then further reduce to 2–6 mg per week

lation for the treatment of transitional cell carcinoma, . By intravenous injection or infusion and regional

papillary bladder tumours and carcinoma in-situ. arterial perfusion , consult product literature

Liposomal formulations of doxorubicin for intravenous Alkeran c

use are also available. They may reduce the incidence of (GSK) A cardiotoxicity and lower the potential for local necrosis,

Tablets , melphalan 2 mg, net price 25 = £11.46 but infusion reactions, sometimes severe, may occur. Injection , powder for reconstitution, melphalan

Hand-foot syndrome (painful, macular reddening skin

50 mg (as hydrochloride). Net price 50-mg vial (with eruptions) occurs commonly with liposomal doxorubi- solvent-diluent) = £27.61

cin and may be dose limiting. It can occur after 2–3

8.1.2 Anthracyclines and other cytotoxic antibiotics BNF 57 treatment cycles and may be prevented by cooling

Dactinomycin is principally used to treat paediatric hands and feet and avoiding socks, gloves, or tight-

cancers; it is given intravenously. Its side-effects are fitting footwear for 4–7 days after treatment.

similar to those of doxorubicin, except that cardiac The Scottish Medicines Consortium has advised (Decem-

toxicity is not a problem. ber 2003) that pegylated liposomal doxorubicin is not

Mitomycin is given intravenously to treat upper gastro- recommended for metastatic breast cancer.

intestinal and breast cancers and by bladder instillation for superficial bladder tumours. It causes delayed bone-

NICE guidance (paclitaxel, pegylated liposo- marrow toxicity and therefore it is usually administered mal doxorubicin and topotecan for second-line

at 6-weekly intervals. Prolonged use may result in or subsequent treatment of advanced ovarian

permanent bone-marrow damage. It may also cause cancer)

lung fibrosis and renal damage. See p. 478

Epirubicin is structurally related to doxorubicin and

BLEOMYCIN

clinical trials suggest that it is as effective in the treat- Indications squamous cell carcinoma; see also notes ment of breast cancer. A maximum cumulative dose of

n above

0.9–1 g/m is recommended to help avoid cardiotoxi- Cautions see section 8.1 and notes above; renal city. Like doxorubicin it is given intravenously and by

impairment (Appendix 3); caution in handling—irri- essio bladder instillation.

tant to tissues

Idarubicin has general properties similar to those of Contra-indications pregnancy (Appendix 4); breast- doxorubicin; it is mostly used in the treatment of hae-

osuppr feeding

matological malignancies. Idarubicin is given intrave- Side-effects see section 8.1 and notes above nously and it may also be given by mouth.

Daunorubicin also has general properties similar to Bleomycin (Non-proprietary) A immun those of doxorubicin. It should be given by intravenous

Injection , powder for reconstitution, bleomycin (as and sulphate). Net price 15 000-unit vial = £15.56 infusion and is indicated for acute leukaemias. A lipo-

somal formulation for intravenous use is licensed for Note To conform to the European Pharmacopoeia vials pre- AIDS-related Kaposi’s sarcoma. viously labelled as containing ‘15 units’ of bleomycin are now labelled as containing 15 000 units. The amount of bleomycin in the vial has not changed.

disease

Use with trastuzumab

Brands include Bleo-Kyowa Concomitant use of anthracyclines with trastuzumab

gnant

(section 8.1.5) is associated with cardiotoxicity; for details, see p. 485.

DACTINOMYCIN Mali

(Actinomycin D) Mitoxantrone (mitozantrone) is structurally related to

8 Indications

doxorubicin; it is used for metastatic breast cancer. see notes above Mitoxantrone is also licensed for use in the treatment Cautions see section 8.1 and notes above; caution in

of non-Hodgkin’s lymphoma and adult non-lymphocytic handling—irritant to tissues leukaemia. It is given intravenously and is well tolerated

Contra-indications pregnancy (Appendix 4); breast- but myelosuppression and dose-related cardiotoxicity

feeding

occur; cardiac examinations are recommended after a Side-effects see section 8.1 and notes above cumulative dose of 160 mg/m .

Cosmegen Lyovac c (Ovation) A Bleomycin is given intravenously or intramuscularly to

Injection , powder for reconstitution, dactinomycin, treat metastatic germ cell cancer and, in some regimens,

net price 500-microgram vial = £6.75 non-Hodgkin’s lymphoma. It causes little bone-marrow suppression but dermatological toxicity is common and increased pigmentation particularly affecting the flex- ures and subcutaneous sclerotic plaques may occur.

DAUNORUBICIN

Mucositis is also relatively common and an association Indications see notes above with Raynaud’s phenomenon is reported. Hypersensi-

Cautions see section 8.1 and notes above; hepatic tivity reactions manifest by chills and fevers commonly

impairment (Appendix 2), renal impairment (Appen- occur a few hours after drug administration and may be

dix 3); caution in handling—irritant to tissues prevented by simultaneous administration of a cortico-

Contra-indications pregnancy (Appendix 4); breast- steroid, for example hydrocortisone intravenously. The

feeding

principal problem associated with the use of bleomycin Side-effects see section 8.1 and notes above is progressive pulmonary fibrosis. This is dose-related, occurring more commonly at cumulative doses greater

Daunorubicin (Non-proprietary) A than 300 000 units (see Bleomycin, below) and in the

Injection , powder for reconstitution, daunorubicin (as elderly. Basal lung crepitations or suspicious chest X-ray

hydrochloride), net price 20-mg vial = £44.76 changes are an indication to stop therapy with this drug.

Note The brand name Cerubidin was formerly used. Patients who have received extensive treatment with bleomycin

Lipid formulation 100 000 units—see Bleomycin below) may be at risk of

(e.g. cumulative

DaunoXome c (Diatos) A developing respiratory failure if a general anaesthetic is

Concentrate for intravenous infusion , daunorubicin given with high inspired oxygen concentrations. Anaes-

encapsulated in liposomes. For dilution before use. thetists should be warned of this.

Net price 50-mg vial = £137.67 For advanced AIDS-related Kaposi’s sarcoma

BNF 57

8.1.2 Anthracyclines and other cytotoxic antibiotics 467