is accepted for restricted use within NHS Scotland in
combination with capecitabine or fluorouracil and
cisplatin for the treatment of patients with HER2 positive
restricted to patients with metastatic gastric cancer whose
tumours have HER2 over-expression, as determined by an
886 Antibody responsive malignancy BNF 78
Immune system and malignant disease
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Herceptin (Roche Products Ltd)
Trastuzumab 120 mg per 1 ml Herceptin 600mg/5ml solution for
injection vials | 1 vial P £1,222.20 (Hospital only)
Powder for solution for infusion
▶ Herceptin (Roche Products Ltd)
Trastuzumab 150 mg Herceptin 150mg powder for concentrate for
solution for infusion vials | 1 vial P £407.40
▶ Herzuma (Napp Pharmaceuticals Ltd) A
Trastuzumab 150 mg Herzuma 150mg powder for concentrate for
solution for infusion vials | 1 vial P £366.66
Trastuzumab 420 mg Herzuma 420mg powder for concentrate for
solution for infusion vials | 1 vial P £1,026.65 (Hospital only)
Trastuzumab 150 mg Kanjinti 150mg powder for concentrate for
solution for infusion vials | 1 vial P £366.66
Trastuzumab 420 mg Kanjinti 420mg powder for concentrate for
solution for infusion vials | 1 vial P £1,026.65 (Hospital only)
▶ Ontruzant (Merck Sharp & Dohme Ltd) A
Trastuzumab 150 mg Ontruzant 150mg powder for concentrate for
solution for infusion vials | 1 vial P £366.66
Trastuzumab 150 mg Trazimera 150mg powder for concentrate for
solution for infusion vials | 1 vial P £366.66 (Hospital only)
Trastuzumab emtansine 02-Aug-2017
linked to DM1, a cytotoxic microtubule inhibitor.
Monotherapy for the treatment of HER2-positive,
unresectable, locally advanced or metastatic breast
cancer, in adult patients who have previously received
trastuzumab and a taxane separately or in combination
(initiated by a specialist)| Monotherapy for the
treatment of HER2-positive, unresectable, locally
advanced or metastatic breast cancer, in adult patients
who have developed disease recurrence during or within
6 months of completing adjuvant therapy (initiated by a
▶ Adult: (consult product literature or local protocols)
l CAUTIONS Dyspnoea at rest—increased risk of pulmonary
events . history of congestive heart failure . patients over
75 years . peripheral neuropathy (temporarily discontinue
treatment—consult product literature).recent history of
literature for specific risks with trastuzumab treatment. serious arrhythmias
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Uncommon Hepatic disorders . nodular regenerative
l CONCEPTION AND CONTRACEPTION Effective
contraception must be used during and for 6 months after
stopping treatment in women and men.
l PREGNANCY Manufacturer advises avoid—
oligohydramnios reported with trastuzumab. See also
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Manufacturer advises avoid breastfeeding during and for 6 months after treatment.
l HEPATIC IMPAIRMENT Consult product literature for
initiating treatment and discontinuation in cases of
abnormal liver function tests.
Dose adjustments Consult product literature for dose
modification in cases of abnormal liver function tests.
l RENAL IMPAIRMENT No information available—
manufacturer advises caution in severe impairment.
▶ Monitor hepatic function before each dose.
▶ Monitor for signs and symptoms of neurotoxicity.
▶ Monitor closely for infusion-related and hypersensitivity
▶ Monitor platelet count before each dose and as clinically
indicated (consult product literature for treatment
modification in thrombocytopenia).
▶ Test cardiac function before treatment and regularly
during treatment—delay or discontinue treatment in cases
of left ventricular dysfunction.
▶ Monitor for dyspnoea, cough, fatigue and pulmonary
infiltrates—discontinue if interstitial lung disease or
pneumonitis confirmed (fatal cases reported).
l DIRECTIONS FOR ADMINISTRATION Resuscitation facilities
should be available during administration of trastuzumab
l PRESCRIBING AND DISPENSING INFORMATION When
prescribing, dispensing or administering, check that this is
the correct preparation— trastuzumab emtansine and
trastuzumab are not interchangeable.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Trastuzumab emtansine for treating HER2-positive advanced
breast cancer after trastuzumab and a taxane (updated
Trastuzumab emtansine is recommended, within its
marketing authorisation, as an option for treating human
epidermal growth factor receptor 2 (HER2)-positive,
unresectable, locally advanced or metastatic breast cancer
in adults who previously received trastuzumab and a
taxane, separately or in combination. Patients should have
either received prior therapy for locally advanced or
metastatic disease or developed disease recurrence during
or within 6 months of completing adjuvant therapy.
Trastuzumab emtansine is recommended only if the
manufacturer provides it with the discount agreed in the
www.nice.org.uk/guidance/TA458
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (April 2017)
that trastuzumab emtansine (Kadcyla ®) is accepted for use
within NHS Scotland as monotherapy for the treatment of
patients with human epidermal growth factor type 2
(HER2)-positive, unresectable locally advanced or
metastatic breast cancer who previously received
trastuzumab and a taxane, separately or in combination,
and have either received prior therapy for locally advanced
or metastatic disease or developed disease recurrence
during or within six months of completing adjuvant
therapy. This advice is contingent upon the continuing
availability of the Patient Access Scheme in NHS Scotland
or a list price that is equivalent or lower.
BNF 78 Antibody responsive malignancy 887
Immune system and malignant disease
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
▶ Kadcyla (Roche Products Ltd)
Trastuzumab emtansine 100 mg Kadcyla 100mg powder for
concentrate for solution for infusion vials | 1 vial P £1,641.01
Trastuzumab emtansine 160 mg Kadcyla 160mg powder for
concentrate for solution for infusion vials | 1 vial P £2,625.62
l DRUG ACTION Telotristat ethyl and its active metabolite
inhibit L-tryptophan hydroxylases TPH-1 and TPH-2
which reduces the production of serotonin, thereby
alleviating symptoms associated with carcinoid syndrome.
Carcinoid syndrome diarrhoea (specialist use only)
▶ Adult: 250 mg 3 times a day, review treatment if no
l INTERACTIONS → Appendix 1: telotristat ethyl
l PREGNANCY Manufacturer advises avoid—toxicity in
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment; avoid in severe impairment
Dose adjustments Manufacturer advises consider dose
reduction to 250 mg twice daily in mild impairment and to
250 mg once daily in moderate impairment, according to
l RENAL IMPAIRMENT Manufacturer advises caution in
mild-to-moderate impairment; avoid in severe
impairment—no information available.
l MONITORING REQUIREMENTS Manufacturer advises
monitor liver function at initiation and during treatment
as clinically indicated—discontinue if liver injury
l PATIENT AND CARER ADVICE Manufacturer advises inform
patients to report any symptoms of depression or
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (June 2018)
that telotristat ethyl (Xermelo ®) is accepted for restricted
use within NHS Scotland for the treatment of carcinoid
syndrome diarrhoea in adults who experience an average
of four or more bowel motions per day, despite receiving
somatostatin analogue therapy. This advice is contingent
upon the continuing availability of the patient access
scheme in NHS Scotland or a list price that is equivalent or
All Wales Medicines Strategy Group (AWMSG) decisions
The All Wales Medicines Strategy Group has advised (July
2018) that telotristat ethyl (Xermelo ®) is recommended as
an option for restricted use within NHS Wales for the
treatment of carcinoid syndrome diarrhoea in adults who
are inadequately controlled by somatostatin analogue
therapy and who experience an average of four or more
bowel movements a day. This recommendation applies
only in circumstances where the approved Wales Patient
Access Scheme (WPAS) is utilised or where the
list/contract price is equivalent or lower than the WPAS
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3, 21
Telotristat ethyl 250 mg Xermelo 250mg tablets | 90 tablet P £1,120.00
The chemotherapy of cancer is complex and should be
confined to specialists in oncology. Cytotoxic drugs have
both anti-cancer activity and the potential to damage
normal tissue; most cytotoxic drugs are teratogenic.
Chemotherapy may be given with a curative intent or it may
aim to prolong life or to palliate symptoms. In an increasing
number of cases chemotherapy may be combined with
radiotherapy or surgery or both as either neoadjuvant
treatment (initial chemotherapy aimed at shrinking the
primary tumour, thereby rendering local therapy less
destructive or more effective) or as adjuvant treatment
(which follows definitive treatment of the primary disease,
when the risk of subclinical metastatic disease is known to be
high). All cytotoxic drugs cause side-effects and a balance
has to be struck between likely benefit and acceptable
Combinations of cytotoxic drugs, as continuous or pulsed
cycles of treatment, are frequently more toxic than single
drugs but have the advantage in certain tumours of
enhanced response, reduced development of drug resistance
Cytotoxic drugs fall into a number of classes, each with
characteristic antitumour activity, sites of action, and
toxicity. A knowledge of sites of metabolism and excretion is
important because impaired drug handling as a result of
disease is not uncommon and may result in enhanced
Cytotoxic drug handling guidelines
. Trained personnel should reconstitute cytotoxics
. Reconstitution should be carried out in designated
. Protective clothing (including gloves, gowns, and masks)
. The eyes should be protected and means of first aid should
. Pregnant staff should avoid exposure to cytotoxic drugs
(all females of child-bearing age should be informed of the
. Use local procedures for dealing with spillages and safe
disposal of waste material, including syringes, containers,
. Staff exposure to cytotoxic drugs should be monitored
Immune system and malignant disease
A Health Service Circular (HSC 2008/001) provides guidance
on the introduction of safe practice in NHS Trusts where
intrathecal chemotherapy is administered; written local
guidance covering all aspects of national guidance should be
available. Support for training programmes is also available.
Copies, and further information may be obtained from:
It is also available from the Department of Health website
Safe systems for cytotoxic medicines
NHS cancer networks have been established across the UK to
bring together all stakeholders in all sectors of care, to work
collaboratively to plan and deliver high quality cancer
services for a given population. NHS cancer networks have
websites containing information on local chemotherapy
. cytotoxic drugs for the treatment of cancer should be given
as part of a wider pathway of care coordinated by a
. cytotoxic drugs should be prescribed, dispensed, and
administered only in the context of a written protocol or
. injectable cytotoxic drugs should only be dispensed if they
are prepared for administration
. oral cytotoxic medicines should be dispensed with clear
Cytotoxic drugs: important safety information
Risk of incorrect dosing of oral anti-cancer medicines
The National Patient Safety Agency has advised (January
2008) that the prescribing and use of oral cytotoxic
medicines should be carried out to the same standard as
. non-specialists who prescribe or administer on-going oral
cytotoxic medication should have access to written
protocols and treatment plans, including guidance on the
monitoring and treatment of toxicity;
. staff dispensing oral cytotoxic medicines should confirm
that the prescribed dose is appropriate for the patient.
Patients should have written information that includes
details of the intended oral anti-cancer regimen, the
treatment plan, and arrangements for monitoring, taken
from the original protocol from the initiating hospital.
Staff dispensing oral cytotoxic medicines should also have
access to this information, and to advice from an
experienced cancer pharmacist in the initiating hospital.
Doses of cytotoxic drugs are determined using a variety of
further adjusted following consideration of a patient’s
neutrophil count, renal and hepatic function, and history of
previous adverse effects to the cytotoxic drug. Doses may
also differ depending on whether a drug is used alone or in
Because of the complexity of dosage regimens in the
treatment of malignant disease, dose statements have been
omitted from some of the drug entries in this chapter.
However, even where dose statements have been provided,
detailed specialist literature, individual hospital
chemotherapy protocols, or local cancer networks should be
consulted before prescribing, dispensing, or administering
Prescriptions should not be repeated except on the
Side-effects common to most cytotoxic drugs are discussed
below whilst side-effects characteristic of a particular drug or
class of drugs (e.g. neurotoxicity with vinca alkaloids) are
mentioned in the appropriate sections. Manufacturers’
side-effects associated with individual drugs and specific
Many side-effects of cytotoxic drugs often do not occur at
the time of administration, but days or weeks later. It is
therefore important that patients and healthcare
professionals can identify symptoms that cause concern and
can contact an expert for advice. Toxicities should be
accurately recorded using a recognised scoring system such
as the Common Toxicity Criteria for Adverse Events (CTCAE)
developed by the National Cancer Institute.
Extravasation of intravenous drugs
A number of cytotoxic drugs will cause severe local tissue
necrosis if leakage into the extravascular compartment
occurs. To reduce the risk of extravasation injury it is
recommended that cytotoxic drugs are administered by
appropriately trained staff. See information on the
prevention and management of extravasation injury.
A sore mouth is a common complication of cancer
chemotherapy; it is most often associated with fluorouracil
p. 910, methotrexate p. 913, and the anthracyclines. It is best
to prevent the complication. Good oral hygiene (rinsing the
mouth frequently and effective brushing of the teeth with a
soft brush 2–3 times daily) is probably beneficial. For
fluorouracil p. 910, sucking ice chips during short infusions
Once a sore mouth has developed, treatment is much less
effective. Saline mouthwashes should be used but there is no
Tumour lysis syndrome occurs secondary to spontaneous or
treatment-related rapid destruction of malignant cells.
Patients at risk of tumour lysis syndrome include those with
non-Hodgkin’s lymphoma (especially if high grade and bulky
disease), Burkitt’s lymphoma, acute lymphoblastic
leukaemia and acute myeloid leukaemia (particularly if high
white blood cell counts or bulky disease), and occasionally
those with solid tumours. Pre-existing hyperuricaemia,
dehydration, and renal impairment are also predisposing
factors. Features include hyperkalaemia, hyperuricaemia
(see below), and hyperphosphataemia with hypocalcaemia;
renal damage and arrhythmias can follow. Early
identification of patients at risk, and initiation of
prophylaxis or therapy for tumour lysis syndrome, is
Hyperuricaemia, which may be present in high-grade
lymphoma and leukaemia, can be markedly worsened by
chemotherapy and is associated with acute renal failure.
Allopurinol p. 1121 should be started 24 hours before
treating such tumours and patients should be adequately
hydrated. The dose of mercaptopurine p. 912 or azathioprine
p. 836 should be reduced if allopurinol needs to be given
concomitantly. Febuxostat p. 1121 may also be used and
should be started 2 days before cytotoxic therapy is initiated.
Rasburicase p. 942, a recombinant urate oxidase, is
licensed for hyperuricaemia in patients with haematological
malignancy. It rapidly reduces plasma-uric acid
BNF 78 Cytotoxic responsive malignancy 889
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