8: Malignant disease and immunosuppression
Please select a topic:
8.1 Cytotoxic drugs
8.2 Drugs affecting the immune response
8.3 Sex hormones and hormone antagonists in malignant disease
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 1 of 10
Date: 18.8.2012
Review Date: 18.8.2013
8.1 Cytotoxic drugs
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.
For recommendations regarding dosage refer to the North of England Cancer Network (or NECN)
Handbook:
http://www.ncn.nhs.uk/hpSite/groups/networkcrosscuttinggroups/chemotherapy
This handbook lists all the approved chemotherapy protocols, which contain details of prescribing
issues, management of toxic effects and supportive care. 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.
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.
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.
The prescribing notes for the following sub-sections have been combined and do not follow the
structure of chapter 8.1 of the BNF.
Most of the oncology drugs listed below are for specialist use only and are not suitable for general
use in primary care. They are listed here for information only. The only oncology drugs that may be
prescribed on occasion by GPs are cyclophosphamide, azathioprine, methotrexate, mercaptopurine
and hydroxycarbamudide (N.B. this would only be where there is a shared care arrangement with
individual GP)
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 2 of 10
Date: 18.8.2012
Review Date: 18.8.2013
Alkylating drugs

Busulfan (Busulphan) 2mg tablets

Chlorambucil 2mg tablets

Cyclophosphamide 50mg tablets – Amber when used for used to suppress inflammatory/autoimmune
condtions

Cyclophosphamide injection

Lomustine 40mg capsules

Melphalan 2mg tablets
Cytotoxic antibiotics

Bleomycin injection

Doxorubicin injection

Doxorubicin lipsomal (Caelyx®) injection

Epirubicin injection

Idarubicin 5mg capsules

Mitomycin injection

Mitoxantrone (Mitozantrone) injection
Antimetabolites

Azacitidine injection

Capecitabine 150mg and 500mg tablets

Cladribine injection

Cytarabine injection

Fludarabine injection

Fludarabine 10mg tablets

Fluorouracil injection

Gemcitabine injection

Mercaptopurine 50mg tablets Amber when used for used to suppress inflammatory/autoimmune conditions

Methotrexate 2.5mg tablets - Amber when used for used to suppress inflammatory/autoimmune

Methotrexate injection

Pemetrexed injection
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 3 of 10
Date: 18.8.2012
Review Date: 18.8.2013
Vinca alkaloids and etoposide

Etoposide 50mg capsules

Etoposide injection

Vinblastine injection

Vincristine injection

Vindesine injection

Vinorelbine injection

Vinorelbine 20mg, 30mg and 80mg capsules
Other antineoplastic drugs

Bevacizumab injection

Bortezomib injection

Carboplatin injection

Cetuximab injection

Cisplatin injection

Dacarbazine injection

Dasatinib 20mg, 50mg, and 70mg tablets

Docetaxel injection

Eribulin injection

Erlotinib 25, 100mg, and 150mg tablets

Gefitinib tablets

Hydroxycarbamide/Hydroxyurea 500mg capsules - Amber when used for used to suppress
inflammatory/autoimmune

Imatinib 100mg and 400mg tablets

Irinotecan injection

Lapatinib 205mg tablets

Lenalidomide 5mg, 10mg, 15mg and 25mg capsules

Nilotinib 200mg capsules

Oxaliplatin injection

Paclitaxel injection

Pentostatin injection (restricted)
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 4 of 10
Date: 18.8.2012
Review Date: 18.8.2013

Procarbazine 50mg capsules

Thalidomide 50mg capsules

Topotecan injection

Trastuzumab injection

Tretinoin 10mg capsules
Drugs for cytotoxic-induced side effects

Calcium folinate 50mg and 300mg injection

Calcium folinate 15mg tablets

Mesna 1g injection

Mesna 400mg tablets
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.
Refer to the North of England Cancer Network (or NECN) Handbook for advice on all supportive
care:
http://www.ncn.nhs.uk/hpSite/groups/networkcrosscuttinggroups/chemotherapy
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 5 of 10
Date: 18.8.2012
Review Date: 18.8.2013
8.2 Drugs affecting the immune response
Antiproliferative immunosuppressants

Azathioprine 25mg and 50mg tablets

Azathioprine 50mg injection

Mycophenolate mofetil 250mg tablets, 500mg capsules, 1g/5ml oral suspension (Cellcept®)
Prescribing notes

Azathioprine should not be given in combination with allopurinol due to myelosuppression.

Patients should be warned to report any signs or symptoms of bone marrow suppression i.e.
infection, bruising and bleeding.

Mycophenolate mofetil is contra-indicated in pregnancy.
Corticosteroids and other immunosuppressants

Ciclosporin/Cyclosporin 25mg, 50mg and 100mg capsules (Neoral®)

Ciclosporin/Cyclosporin 100mg/ml oral solution (Neoral®)

Tacrolimus 500microgram, 1mg and 5mg capsules (Prograf®)
Dose
- Ciclosporin capsules 10mg, 25mg, 50mg, 100mg; oral solution 100mg/mL: 5-8mg/kg/day in 2
divided doses (dose adjusted according to trough levels).
- Tacrolimus (Prograf®) capsules 500 micrograms, 1mg and 5mg: 100 micrograms/kg/day in 2
divided doses (dose adjusted according to trough levels
Prescribing notes

Trough levels should be sampled prior to drug administration.

Target trough levels vary depending on indication

Tacrolimus is contra-indicated in pregnancy (seek specialist advice)

Two formulations of tacrolimus capsules are available: Prograf® for twice daily administration
and Advagraf® for once daily administration. Care should be taken to distinguish clearly
between these two preparations when prescribing and dispensing. Prescribe by
brand name. Patients should only be changed from one preparation to the other,
under supervision of a transplant specialist.
Interferons

Interferon alfa 18 million unit pen

Peg-inferferon alfa injection
Dose
- Dependant on indication. For use under the supervision of hospital specialist. Seek specialist
advice.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 6 of 10
Date: 18.8.2012
Review Date: 18.8.2013
Prescribing notes

Interferon alpha is used for the treatment of chronic myeloid leukaemia, hairy cell leukaemia,
non Hodgkins lymphoma, myeloma, carcinoid tumours, Kaposi?s sarcoma, renal carcinoma,
adjuvant treatment of malignant melanoma.

Peg-interferon alfa is used for the treatment of chronic hepatitis C in combination with
ribavirin.
Monoclonals

Rituximab 500mg and 100mg injection
Dose
- Rituximab concentrate for intravenous infusion 10mg/mL: see product information.
Prescribing notes

Full resuscitation facilities should be at hand and treatment should only be undertaken with
the close supervision of a specialist.

Rituximab may exacerbate angina, arrhythmia and heart failure; transient hypotension
occurs frequently and antihypertensives may need to be withheld for 12 hours before
infusion.

Patients should be given paracetamol and an antihistamine before each dose of rituximab to
reduce the incidence of infusion-related side-effects. Pre-medication with a corticosteroid
should also be considered. See product literature for treatment of infusion-related sideeffects.

Severe cytokine release syndrome has occurred 1-2 hours after infusion of rituximab.
Patients with a high tumour burden as well as those with pulmonary insufficiency or
infiltration are at increased risk and should be monitored very closely.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 7 of 10
Date: 18.8.2012
Review Date: 18.8.2013
8.3 Sex hormones and hormone antagonists in malignant disease
Progestogens

Medroxyprogesterone 100mg, 200mg and 500mg tablets

Megestrol 40mg and 160mg tablets
Dose
Endocrine therapy for cancer should be initiated only on advice from a hospital specialist.
- Medroxyprogesterone acetate tablets 100mg, 200mg, 250mg, 400mg, 500mg: advanced renal
cancer, 300mg daily.
- Megestrol acetate tablets 40mg, 160mg: advanced breast or renal cancer, 160mg daily.
Prescribing notes

Progestogens are rarely used for third-line endocrine therapy in breast cancer and are
occasionally used in frail patients with advanced renal cancer or advanced endometrial
cancer.

Progestogens should be used with caution in conditions that may worsen with fluid retention
and in those susceptible to thromboembolism.

Megestrol can be used for anorexia. Megestrol 40mg daily may also be prescribed for
menopausal symptoms for women receiving endocrine therapy.
Hormone antagonists

Anastrazole 1mg tablets

Exemestane 25mg tablets

Fulvestrant 250mg/5ml pre-filled syringe

Goserelin 3.6mg injection

Letrozole 2.5mg tablets

Tamoxifen 10mg and 20mg tablets

Tamoxifen 10mg/5ml solution
Dose
Endocrine therapy must only be initiated on the advice of a hospital specialist.
-
Tamoxifen tablets 20mg: 20mg daily.
Letrozole tablets 2.5mg: 2.5mg daily.
Anastrozole tablets 1mg: 1mg daily.
Exemestane tablets 25mg: 25mg daily.
Fulvestrant injection 250mg:250mg into the gluteal muscle every 4 weeks
Goserelin implant 3.6mg: 3.6 mg by subcutaneous injection every 28 days.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 8 of 10
Date: 18.8.2012
Review Date: 18.8.2013
Prescribing notes

The aromatase inhibitors letrozole, anastrozole and exemestane are ineffective in
premenopausal women unless concomitant goserelin is given to suppress ovarian function.

Tamoxifen is more effective when ovarian function is suppressed in premenopausal women.
Concomitant goserelin may be given for the first two years of adjuvant tamoxifen therapy in
this group.

Oophorectomy is an alternative to goserelin in premenopausal women.

Tamoxifen increases the risk of venous and arterial thrombosis in postmenopausal women.
Letrozole or anastrozole should be used in patients with an increased risk of
thromboembolism.

Tamoxifen increases the risk of endometrial cancer. Abnormal vaginal bleeding should be
investigated promptly.

Endocrine therapy may cause a transient increase in bone pain in patients with bony
metastases.
Prostate cancer & gonadorelin analogues

Bicalutamide 150mg tablets Consultant Urologists Only

Bicalutamide 50mg tablets

Cyproterone acetate 50mg tablets

Flutamide 250mg tablets

Goserelin 3.6mg injection

Leuprorelin acetate 3.75mg injection

Degarelix 120mg and 80mg injection
Dose
Endocrine therapy must only be initiated on the advice of a hospital specialist.
- Bicalutamide tablets 50mg, 150mg: to prevent tumour flare when a gonadorelin analogue is
started, 50mg daily for three weeks starting 2 weeks before the gonadorelin analogue. Used as a
single agent for locally advanced disease, 150mg daily. Administered concurrently with a
gonadorelin analogue to obtain maximum androgen blockade, 50mg daily.
- Flutamide tablets 250mg: 250mg three times daily.
- Leuprorelin acetate prefilled syringe 3.75mg: by subcutaneous injection, for neo-adjuvant
therapy, 3.75mg every 4 weeks for 3 months.An anti-androgen should be started 2 weeks before
leuprorelin to prevent tumour flare, and continued for 3 weeks in total.
- Goserelin prefilled syringe 3.6mg: by subcutaneous injection, for neo-adjuvant therapy, 3.6mg
every 4 weeks for 3 months. For longer term treatment of locally advanced or metastatic disease,
10.8mg subcutaneously every 3 months. An anti-androgen should be started 2 weeks before
goserelin to prevent tumour flare, and continued for 3 weeks in total.
- Degarelix injection 120mg, 80mg: by subcutaneous injection, initially 240mg (administered as 2
x 120mg injections), then 80mg every 28 days.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 9 of 10
Date: 18.8.2012
Review Date: 18.8.2013
Prescribing notes

Gonadorelin analogues cause side-effects similar to orchidectomy. Both anti-androgens and
gonadorelin analogues may cause gynaecomastia, reduced libido, hot flushes, mood changes
and sweats.

Gonadorelin analogues may cause 'tumour-flare' in the first weeks of treatment with a
transient worsening of pain or ureteric obstruction. This can be prevented by pre-treatment
with an anti-androgen.

Bicalutamide is the first choice of anti-androgen because of its once daily administration
schedule. It should not be used as monotherapy for the treatment of localised prostate
cancer.

Cyproterone 50mg twice daily may be used to treat hot flushes associated with gonadorelin
analogues.

Leuprorelin is licensed for advanced prostate cancer whilst goserelin is licensed for all stages
of prostate cancer.
Somatostatin analogues

Octreotide 50 micrograms/ml, 100 micrograms/ml, 500 micrograms/ml and 1mg/5ml injection
Dose
Endocrine therapy must only be initiated on the advice of a hospital specialist.
- Octreotide injection 50micrograms/mL, 100micrograms/mL, 200micrograms/mL,
500micrograms/mL: for initial treatment of carcinoid syndrome, 50micrograms by subcutaneous
injection once or twice daily, increasing if necessary to 200micrograms three times daily.
Prescribing notes

Somatostatin analogues are used for the relief of symptoms associated with neuroendocrine
tumours, particularly carcinoid syndrome.

Thyroid function should be checked every 12 months.

Treatment may cause diarrhoea.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default
Amber 1 = Drugs with shared care agreement
Amber 2 = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Drug & Therapeutics Committee
Page 10 of 10
Date: 18.8.2012
Review Date: 18.8.2013