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8.0 Malignant Disease and Immunosuppression

8.0 Malignant Disease and Immunosuppression

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, and recommendations for use are beyond the scope of this document. Specialists prescribing cytotoxic treatment should refer to the relevant East Lancashire treatment 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.

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.

Bone marrow suppression

  • 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.

Nausea and vomiting

  • 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.

Vesicant drugs  

  • 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.

Hypersensitivity/allergy  

  • 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.

Gastro-intestinal toxicity 

  • 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,
  • 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.

Neurotoxicity

  • 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.

Renal/urothelial toxicity

  • 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.

Cardiac toxicity

  • 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.

Important interactions

  • Reduce doses of mercaptopurine and azathioprine when given with allopurinol.
  • Procarbazine interacts with alcohol.
  • Capecitabine may potentiate warfarin.

Cutaneous reactions 

  • The course of capecitabine should be discontinued in the event of painful hands and soles of feet interfering with function, and specialist advice obtained.

8.1 Cytotoxic drugs

Drugs for cytotoxic-induced side-effects
RED           Calcium Folinate
                   injection 3mg/1ml, 10mg/ml, 15mg/2mL
AMBER     Calcium Folinate tablets 15mg
RED           Calcium Levofolinate injection 10mg/mL
RED           Dexrazoxane (Savene®) intravenous infusion
RED           Mesna injection 1g/10mL
RED           Mesna tablets 400mg

8.1.1 Alkylating drugs 
RED           Busulphan tablets 2mg
RED           Carmustine implant 7.7mg
RED           Chlorambucil tablets 2mg
RED           Cyclophosphamide
                   tablets (25mg Named Patient), 50mg
                   injection 200mg, 500mg, 1g,
                   infusion 2g, 4g
RED           Estramustine capsules 140mg
RED           Ifosfamide injection 1g, 2g
RED           Lomustine capsules 40mg
RED           Melphalan
                   tablets 2mg
                   injection 50mg

8.1.2 Cytotoxic antibiotics
RED           Bleomycin injection 15000units/vial  
RED           Doxorubicin injection 10mg/5ml, 50mg/25mL
RED           Doxorubicin liposomal injection 50mg/25mL (NICE indication only)
RED           Doxorubicin beads (DebTox® TACE)
RED           Epirubicin injection 50mg/25mL
RED           Idarubicin capsules 10mg
RED           Liposomal cytarabine-daunorubicin - recommended as an option for untreated therapy-related acute 
                   myeloid leukaemia with myelodysplasia-related changes in adults - as per NICE TA552  
                                                                                                                                                           NHS England Commissioned
RED           Mitomycin injection 40mg
RED           Mitoxantrone injection 20mg/10mL
RED           Pixantrone Injection 29mg (NICE TAG306 use only)
RED           Pegylated liposomal doxorubicin hydrochloride (Caelyx®) - as monotherpay recommended     
                   (within its marketing authoristaion) as an option for treating recurrent ovarian cancer NICE   TA389)                
RED           Pegylated liposomal doxorubicin hydrochloride (Caelyx®) - in combination with platinum 
                  recommended as an option for treating recurrent ovarian cancer NICE TA389     
RED           Pemetrexed (disodium) injection 100mg, 500mg   recommended as an option for maintenance treatment of
                   locally advanced or metastatic non‑squamous non‑small‑cell lung cancer in adults as per NICE  TA402  
                   (replacing TA309)
RED           Pemetrexed (disodium) - maintenance treatment of non-small-cell lung cancer  
                   as per NICE TA190 (text updated August 2017)
8.1.3 Antimetabolites
 
RED           Capecitabine tablets 150mg, 500mg (NICE indication only)
RED           Cladribine injection 10mg/10ml
RED           Cladribine injection 10mg/10ml NICE TA493          NHS England Commissioned 
RED           Cytarabine injection 100mg/1mL
RED           Fludarabine
                                        tablets 10mg
                                        injection 50mg
RED           Fluorouracil injection 500mg/20mL, 2.5g/100mL
RED           Fluorouracil cream 5% - for use in treatment of basal cell carcinoma
RED           Gemcitabine injection 200mg, 1g
RED           Mercaptopurine tablets 50mg 
                  NB (AMBER for Crohn's and UC only, otherwise RED
AMBER     Methotrexate tablets 2.5mg
Shared Care
RED           Methotrexate 
                  injection 50mg/2mL, 5mg/2mL
                  tablets 10mg
RED           Azacitidine injection 100mg
RED           Pemetrexed (disodium) injection 100mg, 500mg   recommended as an option for maintenance treatment
                  of  locally advanced or metastatic non‑squamous non‑small‑cell lung cancer in adults  as per NICE  TA402
                   (replacing TA309) 

 8.1.4 Vinca alkaloids and etoposide 
RED            Etoposide 
                   capsules 50mg, 100mg
                   injection 100mg/5mL
RED           Vinblastine injection 10mg 
RED           Vincristine injection 2mg/2mL
RED           Vinorelbine
                   injection 10mg/1mL
                   capsules 20mg, 30mg


8.1.5 Other antineoplastic drugs   [click here for indications and NICE Guidance]
RED           Aflibercept recommended within its marketing authorisation as an option for treating visual impairment 
                   because of myopic choroidal neovascularisation 
RED           Afatinib tablets 20mg, 30mg, 40mg,50mg in line with NICE TA310 is recommended as an option for
                   metastatic urothelial carcinoma in adults, for  whomcisplatin-based chemotherpay is unsuitable,  
                   only if conditions of  the managed access agreement are followed.                (NHS England Cancer Drugs Fund)
RED           Alectinib recommended as an option for untreated anaplastic lymphoma kinase (ALK)-positive advanced 
                   non-small-cell cancer in adults - as per NICE TA536                                             (NHS England Commissioned) 
RED           Arsenic trioxide is recommended, within its marketing authorisation, as an option for inducing remission 
                   and consolidation in acute promyelocytic leukaemia as per NICE TA526         (NHS England Commissioned)
RED           Atezolizumab -  for use within the Cancer Drugs Fund as an option for untreated locally advanced or 
                   metastatic urothelial carcinoma in adults, for  whom cisplatin-based chemotherpay is unsuitable , only if 
                   conditions of  the managed access agreement are followed as per NICE TA492  
                    (Guidance updated July 2018:  The European medicines Agency restricted the use of Atezolizumab for untreated
                   urothelial carcinoma. It should now only be used in adults with high levels of PD-L1. For more information, see 
                   thesummary of product characteristics for atezolizumab.                               (NHS England Cancer Drugs Fund)
RED           Atezolizumab - for treating locally advanced or metastatic non-small-cell lung cancer after chemotherapy.
                   recommended as an option in NICE TA520 in adults who have had chemotherapy (and targeted treatment if 
                   they have an EGFR- or ALK‑positive tumour), only if:
                      >     atezolizumab is stopped at 2 years of uninterrupted treatment or earlier if the disease progresses and 
                      >     the company provides atezolizumab with the discount agreed in the patient access scheme. 
                                                                                                                                                       (NHS England Commissioned) 
RED           Atezolizumab - for treating locally advanced or metastatic urothelial carcinoma after platinum-containing 
                   chemotherapy. Recommended as an option in NICE TA525 only if:
                           >     atezolizumab is stopped at 2 years of interrupted treatment or earlier if the disease progresses and 
                           >     the company provides atezolizumab with discount agreed in the patient access scheme
                                                                                                                                                       (NHS England Commissioned) 
RED           Axitinib tablets 1mg, 3mg, 5mg, 7mg  as per NICE TA333
RED           Bortezomib injection 3.5mg in line with NICE TA311
RED           Bortezomib injection 3.5mg for previously untreated mantle cell lymphoma in line with NICE TA370  
RED           Bosutinib tablets 100mg, 500mg recommended as an option, by NICE TA401  within its marketing                                       authorisation, for chronic accelerated and blast phase Philadelphia chromosome positive chronic myeloid
                   leukaemia in adults, when:
                           >    they have previously had 1 or more tyrosine kinase inhibitor and         
                           >    imatinib,  nilotinib and dasatinib are not appropriate and
                           >    the company provides bosutinib with the discount agreed in the patient access scheme 
                                   (as revised in 2016)
RED           Brentuximab vedotin 50mg powder for solution for infusion (Adcetris) is recommended  as an option for 
                   treating CD30- positive Hodgkin lymphoma in adults with relapsed or refractory disease only as specified 
                   in NICE TA524 This guidance is a Cancer drugs Fund reconsideration of NICE TA446 . This replaces TA446                                                                                                                                                             (NHS England Cancer Drugs Fund)       
RED           Brentuximab 50mg powder for solution for infusion (Adcetris) is recommended as an option for treating 
                   relapsed or refractory systemic anapplastic large cell  lymphoma in adults as per NICE TA478        
                                                                                                                                                      (NHS England Commissioned) 
RED           Brentuximab 50mg powder for solution for infusion (Adcetris) is recommended as an option for 
                   treating CD30-positive Hodgkin lymphoma in adults as per NICE TA446          (NHS England Commissioned)  
RED           Cabazitaxel in combination with prednisone or prednisolone is recommended an option for treating 
                   metastatic hormone-relapsed prostate cancer in people whose disease has progressed during or after
                   docetaxel chemotherapy in NICE TA391 
RED           Cabozantinib as an option for treating advanced renal cell carcinoma in adults after vascular endothelial 
                   growth factor-targeted therapy as per NICE TA463                                            (NHS England Commissioned) 
RED           Cabozanitinib recommended , within its marketing authorisation, as an option for treating progressive 
                   medullary thyroid cancer in adults with unresectable, locally advanced or metastatic  disease as 
                   per NICE TA516                                                                                                       (NHS England Cancer Drugs Fund) 
RED           Cabozantinib is recommended, within its marketing authorisation, for adults with untreated advanced renal 
                  cell carcinoma that is intermediate - or poor- risk as defined in the International Metaststaic Renal Cell 
                  Carcinoma Database Consortium criteria - as in NICE TA542                        (NHS England Commissioned)     
RED             Carboplatin injection 150mg/15mL, 450mg/45mL
RED           Carfilzomib powder For solution for infusion NICE TA457
RED           Ceritinib capsules 150mg for previously treated anaplastic lymphoma kinase positive non-small-cell lung 
                   cancer as per NICE TA395
RED           Ceritininb - within its marketing authorisation, is recommended as an option for untreated ALK-positive 
                   non-small-cell lung cancer - NICE TA500                                                               (NHS England Commissioned) 
RED           Ceritininb - within its marketing authorisation, is recommended as an  option for untreated ALK-positive 
                  non-small-cell lung cancer - NICE TA500                                                                 (NHS England Commissioned)
RED           Cetuximab infusion 5mg/mL 
RED           Cetuximab is recommended, as an option for previously untreated metastatic colorectal cancer  as per
                   NICE TA 439 (updated Sept 2017)
RED           Cetuximab in combination with platinum based chemotherapy is recommended as an option for treating
                   recurrent or metastatic squamous cell cancer of the head and neck in adults only as per NICE TA473 
                                                                                                                                                        (NHS England Commissioned)  
RED           Cisplatin injection 50mg
RED           Crizotininb  capsules 200mg, 250mg  NICE TA406                                               (NHS England Commissioned) 
RED           Crizotininb  capsules 200mg, 250mg  an option in previously treated anaplastic lymphoma kinase-positive 
                  advanced non-small-cell lung cancer in adults as per  NICE TA422    
RED           Crizotinib is recommended for use within the Cancer Drugs Fund as an option for treating ROS1- positive 
                   advancednon-small-cell lung cancer in adults only if the conditions in the managed access agreement are 
                   followed - NICE TA529                                                                                              (NHS England Cancer Drugs Fund)
RED           Dabrafenib Capsules, 50 mg, 75 mg  NICE TAG 321
RED           Dabrafenib with trametinib is recommended, within its marketing authorisation, an option for the adjuvant 
                   treatment of resected stage III BRAF V600 mutation-positivemelanoma in adults as per NICE TA544 
                                                                                                                                                         (NHS England Commissioned)  
RED           Daratumumab monotherapy for treating relapsed and refractory multiple myeloma  as per NICE TA510
 
RED           Dasatinib tablets 20mg, 50mg, 80mg, 100mg,140mg option in treating only chronic- or accelerated-phase 
                   Philadelphia-chromosome-positive chronic myeloid leukaemia in adults as per NICE TA425
                   Replaces NICE TA241                                                                                                (NHS England Commissioned)  
RED           Dasatinib tablets 20mg, 50mg, 80mg, 100mg,140mg as an  option for untreated chronic-phase Philadelphia-
                   chromosome-positive chronic myeloid leukaemia in adults as per NICE TA426.  Replaces NICE TA251 
                                                                                                                                                        (NHS England Commissioned) 
RED           Dacarbazine injection 1g
RED           Dinutuximab beta - is recommended as an option for treatin g high-risk neuroblastoma in people aged 12 
                   months and over whose disease has at least partially responded to induction chemotherapy, followed by 
                   myeloablative therapy and stem cell transplant  - as per NICE TA538             (NHS England Commissioned)   
RED           Docetaxel injection 20mg/0.5ml, 80mg/2ml (NICE indications only)
RED           Eribulin solution for injection 0.8mg/2ml, 1.32mg/3ml. An option in treating locally advanced or metastatic
                   breast cancer in adults who have had 2 or more courses of chemotherapy as per NICE TA423 
                   (replaces NICE TA250)                                                                                                 (NHS England Commissioned)     
RED           Erlotinib tablets 25mg, 100mg, 150mg (NICE indication only)
RED           Erlotinib tablets 25mg, 100mg, 150mg - treating non-small-cell lung cancer that has progressed after 
                   prior chemotherapy - NICE TA374
RED           Everolimus 2.5mg, 5mg, 10mg  tablets, in combination with exemestane is recommended as an option for                        treating advanced breast cancer  after endocrine therapy - NICE TA421       (NHS England Commissioned)        
RED           Everolimus tablets 2.5mg, 5mg, 10mg recommended as an option for treating advanced renal cell  
                   carcinoma that has progressed during or after treatment  with vascular endothelial growth factor targeted  
                   therapy, only if the company provides it with the discount agreed in the patient access scheme. NICE TA432
                                                                                                                                                        (NHS England Commissioned) 
RED           Everolimus tablets 2.5mg, 5mg, 10mg recommended as an option treating well-  or moderatley
                   differentiated unresectable or metastatic neuroendocrine tumours (NETs) of pancreatic origin
                   in adults with progressive  disease.       NICE TA 449                                           (NHS England Commissioned) 
RED           Hydroxycarbamide capsules 500mg
AMBER     Hydroxycarbamide capsules 500mg - unlicensed use for psoriasis in adults. Specialist  initiation only.
                  See Drug Monitoring in Primary Care for monitoring   requirements
RED           Gefitinib tablets 250mg  as per NICE TA192
RED           Gemtuzumab oxogamicin, with daunorubicin and cytarabine is recommended as an option for untreated 
                   de novo CD33-positive acute myeloid leukaemia in people aged 15 years and over - as in NICE TA545 
                                                                                                                                                    (NHS England Commissioned)
RED            Ibrutinib is recommended as an option for treating relapsed or refractory mantle cell lymphoma in adults                       only if they have had 1 previous line of  therapy and the company provides ibrutinib with the agreed                                   discount in the  commercial access agreement with NHS England  as in NICE TA502
                                                                                                                                                         (NHS England Commissioned)
RED           Ibrutinib capsules 140mg as an option for treating chronic lymphocytic leukaemia in adults who have had at 
                  least 1prior therapy or, who have a 17p deletion or TP53 mutation, and in whom chemotherapy is 
RED           Idelalisib (Zydelig®) tablets 100mg, 150mg - as an option in NICE TA359 for treating chronic
                   lymphocytic leukaemia
RED           Imatinib tablets 100mg, 400mg (NICE TAG326)
RED           Imatinib tablets 100mg, 400mg  option in treating only chronic- or accelerated-phase        
                   Philadelphia-chromosome-positive chronic myeloid leukaemia in adults as per NICE TA425
                   Replaces NICE TA241                                                                                              (NHS England Commissioned)  
RED           Imatinib tablets 100mg, 400mg is recommended as an option for untreated, chronic-phase Philadelphia- 
                   chromosome-positive chronic myeloid leukaemia in adults. NICE TA426  (Replaces NICE TA251)
RED           Ipilimumab IV infusion 5mg/mL (NICE indications only as below)
                  NICE TAG319 - as an possible treatment in previously untreated advanced (unresectable or metastatic)                                 melanoma 
                  NICE TA268 as a possible treatment for people with previously treated advanced (unresectable                                             or metastatic) melanoma 
RED           Irinotecan concentrate for infusion 20mg/mL (NICE indication only)
RED           Ixazomib with lenalinomide and dexamethasone an option for use within the Cancer Drugs Fund for 
                  the treatment of relapsed or refractory multiple myeloma in adults as per NICE TA505
                                                                                                                                                           (NHS England Commissioned)
RED           Lenvatinib is recommended as an option for untreated, advanced, unrescetable hepatocellular carcinoma 
                  in adults,as per NICE TA551                                                                                         (NHS England Commissioned) 
 
RED           Lenvatinib with everolimus for previously treated advanced renal cell  
                  carcinoma as an option as per NICE TA498                                                             (NHS England Commissioned)
RED           Levatininb and sorafenib recommended as options for treating progressive, locally advanced or metastatic
                   differentiated thyroid cancer (papillary, follicular or Hurthle cell) in adults whose disease does not respond
                   to radioactive iodine - as per NICE TA535                                                                (NHS England Commissioned) 
RED           Lutetium (177Lu) oxodotreotide recommended as an option for treating unresectable or metastatic, 
                   progressive, well-differentiated  (grade 1 or grade 2), somatostatin receptor-positive gastroenteropancreatic 
                   neuroendocrine tumours in adults - as per NICE TA539                                       (NHS England Commissioned)
RED           Nilotinib capsules 150mg, 200mg as an option for untreated chronic-phase Philadelphia-chromosome-                             positive chronic myeloid leukaemia in adults as per NICE TA426  (Replaces NICE TA251)
                                                                                                                                                           (NHS England Commissioned) 
RED          Nilotinib capsules 150mg, 200mg option in treating only chronic- or accelerated-phase   
                  Philadelphia-chromosome-positive chronic myeloid leukaemia in adults as per NICE TA425
                  Replaces NICE TA241                                                                                                   (NHS England Commissioned) 
RED          Niraparib - recommended for use within the cancer drugs fund as an option for treating relapsed, platinum-
                  sensitive high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer - as per 
                  NICE TA52                                                                                                                  (NHS England Cancer Drug Fund)
 
RED          Nivolumab  intravenous infusion 10mg/ml is recommended as an option by  NICE for treating advanced 
                  (unresectable or metastatic) melanoma. NICE TA384
RED          Nivolumab in combination with ipilimumab is recommended, within its marketing authorisation, as an 
                 option for treating advanced (unresectable or metastatic) melanoma in adults, only when the company 
                 provides ipilimumab with the discount agreed in the patient access scheme. NICE TA400.       
RED          Nivolumab is recommended as an option for previously treated advanced renal cell carcinoma in adults.   
                  NICE TA417.                                                                                                                                  (NHS England Commissioned)    
                  (updated September 2017 after a change  to the commercial arrangements)
RED          Nivolumab  is recommended as an option for treating relapsed or refractory classical Hodgkin lymphoma
                  in adults after autologous stem cell transplant and  treatment with brentuximab vedotin as per NICE TA462
                   (updated September 2017 after a change to the commercial arrangements)
RED           Obinutuzumab - recommended as an option for untreated advanced follicular lymphoma as per NICE TA513
                                                                                                                                                          (NHS England Commissioned) 
RED          Olaparib 50mg capsules - recommended as an option by NICE for maintenance treatment of relapsed,  
                  platinum-sensitive, BRCA mutation-positive ovarian, fallopian tube and peritoneal cancer after response
                  to second-line or subsequent platinum-based chemotherapy, NICE TA381
RED          Olaratumab, solution for infusion, in combination with doxorubicin is recommended as an option for                                advanced soft tissue sarcoma in adults as per NICE TA465                                 (NHS England Commissioned)
RED          Osimertinib 40mg, 50mg f/c tablets - recommended as an option for use within the Cancer Drugs Fund for
                  treating locally advanced or metastatic EGFR T790M mutation-positive non-small-lung cancer    NICE TA416                                                                                                                                                              (NHS England Commissioned) 
RED            Oxaliplatin injection 50mg, 100mg (NICE indication only)                                                                                            RED           Paclitaxel injection 30mg/5ml (NICE indication only)                    
RED           Paclitaxel Iv infusion - in combination with platinum as an option for treating recurrent ovarian cancer
                   in - NICE TA389
RED           Paclitaxel as albumin-bound nanoparticles with gemcitabine for untreated metastatic pancreatic cancer 
                  - an option by NICE TA476 (replaces TA360)
RED           Palbociclib - with an aromatase inhibitor, is recommended within its marketing authroisation, as an option  
                   for treating hormone receptor-positive , human epidermal growth receptor 2-negative, locally advanced
                   or metastatic  breast cancer as initial endocrine-based therapy in adults NICE TA495
RED           Panitumumab is recommended, as an option for previously untreated metastatic colorectal cancer
                  as per NICE TA 439 (updated Sept 2017)
RED            Panobinostat 20mg tablets - recommended as an option by NICE for treating multiple myeloma after  
                  at least two previous treatments. NICE TA380
RED           Pazopanib Tablets, f/c - recommended as a first-line treatment option for people with advanced renal 
                   cell carcinoma in NICE TA215
RED           Pegaspargase as an option for treating acute lymphoblastic leukaemia in children, young people and adults
                  only when they have untreated newly diagnosed disease, (as part of antineoplastic combination therapy)  in                     NICE TA408
RED           Pembrolizumab as an option for treating locally advanced or metastatic PD-L1-positive non-small-cell lung                      cancer in adults who have had at least one chemotherapy as per NICE TA428   (NHS England Commissioned)  
RED           Pembrolizumab for use within the Cancer Drugs Fund as an option by NICE  TA447 for untreated PD-L1-                            positive  metastatic non-small-cell lung cancer in  adults 
RED           Pembrolizumab - recommended as an option for treating locally advanced or metastatic urothelial 
                   carcinoma after  platinum-containing chemotherapy as per NICE TA519
RED           Pembrolizumab - recommended for use within the Cancer drugs Fund as an option for untreated locally 
                   advancedor metastatic carcinoma in adults when cisplatin-containing chemotherapy is unsuitable - as 
                   per NICE TA522.  (Guidance updated July 2018: The European medicines Agency restricted the use of 
                   pembrolizumab for untreated  urothelial carcinoma. It should now only be used in adults with high levels 
                    of PD-L1. For more information, see the summary of product characteristics for pembrolizumab).
                                                                                                                                                          (NHS England Cancer Drug Fund)
RED          Pembrolizumab is recommended for use within the Cancer Drug Fund as an option for the adjuvant  
                  treatment of Stage III melanoma with lymph node involvement in adults who have  had complete 
                  resection - as per NICE TA553                                                                                   (NHS England Cancer Drug Fund) 
RED           Pembrolizumab is recommended as an option for untreated PD-L1 positive metastatic non-small-cell lung 
                   cancer in adults whose tumours express PD-L1 (with at least 50% tumour proportion score) and have no 
                   (replaces NICE TA447)                                                                                                  (NHS England Commissioned
RED          Pembrolizumab is receommended as an option for treating relapsed or refractory classical Hodgkin 
                  lymphoma in adults who have has brentuximab vedotin and cannot have autologous  stem cell
                  transplant  as in NICE TA540                                                                                      (NHS England Cancer Drug Fund)
RED         Pentostatin injection 10mg  
RED           Pertuzumab solution for infusion 30mg/mL - an option for the neoadjuvant treatment of adults with human                    epidermal growth factor receptor 2 (HER2)‑positive breast cancer, in combination with trastuzumab and                            chemotherapy, as per NICE TA424
RED           Pertuzumab  HER2-positive metastatic or locally recurrent unrescetable breast cancer in adults who have  
                  not had previous anti‑HER2 therapy or chemotherapy for their metastatic disease (in combination with 
                  trastuzumab and docetaxel -  NICE TA509
RED          Ponatinib - Recommended as per NICE TA451 as an option for treating chronic-accelerated  -or blast - phase
                  chronic myeloid leukaemia in adults.                                                                      (NHS England Commissioned)
RED          Procarbazine capsules 50mg
RED          Radium-223 dichloride recommended as an option by NICE for treating hormone-relapsed pro state cancer
                  with bone metastases. NICE TA376 
RED           Regorafenib recommended as an option for treating unresectable or metastatic gastrointestinal stromal
                   tumours in adults whose disease has progressed on, or who are intolerant to, prior treatment with
                   imitinib and sunitinib, as per   NICE TA488                                                               (NHS England Commissioned)
RED           Ribociclib with an aromatase inhibitor, is recommended within its marketing authorisation, as an option
                  for treating hormone receptor-positive, human epidermal growth factor receptor 2‑negative, locally 
                  advanced or metastatic breast cancer as initial endocrine-based therapy in adults. Ribociclib is
                  recommended only if the company provides it with the discount agreed   in the patient access scheme.
RED           Ribociclib with an aromatase inhibitor, is recommended within its marketing authorisation, as an option
                  for treating hormone receptor-positive, human epidermal growth factor receptor 2‑negative, locally 
                  advanced or metastatic breast cancer as initial endocrine-based therapy in adults. Ribociclib is
                  recommended only if the company provides it with the discount agreed in the patient access scheme.
                  NICE TA496
RED           Ruxolitinib tablets 5mg,10mg.15mg,20mg NICE TA386 
RED          Sorafenib tablets 200mg recommended as an option for treating hepatocellular carcinoma only for people
                  with Child-Pugh grade A liver  impairment as per NICE TA474
RED          Sunitinib capsules 12.5mg, 25mg, 50mg
RED          Sunitinib capsules 12.5mg, 25mg, 50mg recommended as an option treating well-  or moderately                                       differentiated unresectable or metastatic neuroendocrine tumours (NETs) of pancreatic origin in adults with 
                 progressive  disease.  NICE TA 449                                                                            (NHS England Commissioned)
RED          Temozolomide capsules 5mg, 20mg, 100mg,140mg, 180mg,250mg NICE TA23    (updated March 2016)
RED           Tisagenlecleucal is recommended for use within the cancer drug fund as an option for treating relapsed or 
                   refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years , as per NICE TA554   
                                                                                                                                                           (NHS England Cancer Drug Fund)
RED           Tivozanib - an option in advanced renal cell carcinoma in adults as per NICE TA512  
                                                                                                                                                          (NHS England Commissioned)
RED          Topetecan infusion Ovarian cancer (NICE TA91) 
RED          Topetecan infusion cervical cancer, recurrent                                                       (NHS England Commissioned)
RED          Trabectedin powder for concentrate 0.25mg, 1mg (Yondelis®) as an treatment option  for people with   
                 advanced soft tissue sarcoma as per NICE TA185
RED          Trametininb tablets 0.5mg, 2mg as an option by NICE for treating unresectable or metastatic melanoma
                 in combination with darbrafenib - NICE TA396
RED          Trastuzumab injection 150mg (NICE indications only) 
RED          Trastuzumab emtansine (Kadcyla) NICE TA458
RED          Trastuzumab emtansine (Kadcyla) - recommended , within its marketing   authorisation, as an option
                  for treating human epidermal growth factor receptor (HER2) - positive, unrescetable, locally advanced or
                  metastatic breast cancer in adults who previously received trastuzumab and a taxane, separately or in 
                  combination as per NICE TA458 updated (replaces TA371)                              (NHS England Cancer Drug Fund)
RED          Tretinoin capsules 10mg
                 (Consultant haematologist only – use whilst waiting transfer to specialist centre - see relevant protocol)
RED          Trifluridine-tipiracil tablets 15mg, 20mg - as per NICE TA405 
RED          Vemfurafenib tablets 240mg 
RED          Venetoclax - as an option within the Cancer Drugs Fund , within its marketing  authorisation, for treating 
                  chronic lymphocytic leukaemia as per NICE TA487

8.2.1 Antiproliferative immunosuppressants

AMBER     Azathioprine tablets 25mg, 50mg
RED           Azathioprine injection 50mg
AMBER     Mycophenolic acid tablets 180mg, 360mg (Myfortic®) - please prescribe by brand.    
                   (Please see exceptions to use covered by NICE guidance in the black traffic light list)
 
Mycophenolate Mofetil - Renal transplantation NICE TA85 & NICE TA99 
RED for new patients       
 
RED            Mycophenolate Mofetil (CellCept®) please prescribe by brand.                         (NHS England Commissioned) 
                   capsules 250mg,  tablets 500mg
 
RED           Mycophenolate Mofetil (CellCept®) - please prescribe by brand. 
                   capsules 250mg , tablets 500mg
                   (Unlicensed indications under full supervision of the consultant) 


8.2.2 Corticosteroids and other immunosuppressants

AMBER     Ciclosporin (Neoral®)
                   capsules 25mg, 50mg, 100mg
                   solution 100mg/mL
 RED           Ciclosporin injection 50mg/mL

NICE Guidance in Immunosuppressive therapy for kidney transplant in adults and children and young people
NICE TA481(replaces TA85) and NICE TA482 (replaces TA99) make recommendations on using the following drugs after kidney transplant.
                                                                                                  
RED          Tacrolimus (immediate release)  
                  (Adoport®, Capexion®, Vivodex, Modigraf®, Prograf®, Tacni®)                         (NHS England Commissioned) 
RED          Mycophenolate mofetil (Cellcept®, non-branded versions)                                 (NHS England Commissioned) 
RED          Basiliximiab (Simulect®)                                                                                            (NHS England Commissioned) 


8.2.3 
Other Anti-lymphocyte monoclonal antibodies

RED            Almetuzumab
                   Concentrate for intravenous infusion
                   Approved as an option for use in line with NICE guidance TAG312 for the treatment of relapsing-remitting
 
RED           Ocrelizumab 
                   Concentrate for solution for infusion  (Ocrevus 300mg/10mL)
                   Approved as an option for use in line with NICE TA533 for the treatment of relapsing-remitting multiple 
                  sclerosis in adults                                                                                                     (NHS England Commissioned) 
 
RED            Avelumab                                                                                                                 (NHS England Cancer Drugs Fund)
                   Concentrate for solution for infusion (Bavencio® 200mg/10ml)
                   Recommended as an option for treating metastatic Merkel Cell carcinoma - NICE TA517
 
RED            Idelalisib 
                    Approved for treating chronic lymphocytic leukaemia (TAG 359) in line with NICE.     
 
RED          Inotuzumab ozogamicin
                  An option for treating relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia 
                  in adults.People with relapse or refractory Philadelphia-chromosome -positive disease should have at least 1 
                  tyrosine kinase inhibitor. In line with NICE TA541                                              (NHS England Commissioned) 
 
RED           Obinutuzumab
                  Concentrate for intravenous infusion
Approved as an option for use in line with NICE TAG343 for untreated chronic lymphocytic leukaemia, in  combination
with chlorambucil. 
Approved as an option for use in line with NICE TA472 for follicular lymphoma refractory to rituximab in combination
with bendamustine.
 
RED            Ofatumumab
                    Concentrate for intravenous infusion
Approved as an option for use in line with NICE TAG344 for untreated chronic lymphocytic leukaemia, in combination with chlorambucil or bendamustine.
 
RED           Pembrolizumab for treating advanced melanoma after disease progression with ipilimumab (TAG 357) is
Pembrolizumab is recommended as an option for treating advanced (unresectable or metastatic) melanoma that has not been previously treated with ipilimumab, in adults. NICE TA366 

RED            Pembrolizumab (Keytruda®) for intravenous infusion


Rituximab
Rituximab is approved for use in line with NICE guidance. 

 

Rituximab in Idiopathic Thrombocytopenia
Rituximab should only be prescribed by a consultant haematologist for eligible patients as outlined below:
           >     Patients with ITP that require treatment because they are at risk of significant bleeding should initially be 
                  treated with prednisolone at a dose of 1-2mg/kg per day. Treatment is continued until the platelet count
                  exceeds 50 x 109/l or the patient fails to respond by 3-4 weeks.
           >     Patients who are intolerant of, or do not respond to corticosteroids should be treated with intravenous
                  immunoglobulin (IVIG) 1g/kg per day for 2 days.
           >     Splenectomy should be considered in patients who do not respond to treatment with steroids or IVIG
           >     Patients who do not respond to steroids or IVIG or who are not considered suitable for surgery may receive
                  treatment with rituximab although unlicenced.
           >      In patients who have relapsed after splenectomy a search should be made for accessory splenic tissue,
                   and rituximab may then be considered.
 
Whether the use of rituximab in accordance with the above criteria is appropriate in any particular case is a matter for 
the treating clinician's professional judgement, having weighed the risks and benefits to the patient and acting in 
accordance with a responsible body of medical opinion, following informed consent from the patient.
 
A new drug review for rituximab in idiopathic thrombocytopenia is available online - click here to access it.
 
Rituximab in ANCA Positive Vasculitis 
Rituximab should only be prescribed by a consultant rheumatologist for eligible patients for the management 
of anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis in situations where standard treatment 
(cyclophosphamide, methotrexate, azathioprine, corticosteroids, and plasma exchange) is not appropriate, not 
tolerated or not effective.
 
A new drug review for rituximab in ANCA Positive Vasculitis is available online - click here to access it 
NHS England Clinical Commissioning Policy: Rituximab for Anti-Neutrophil Cytoplasmic Antibody-associated 
vasculitis is available here
 
Rituximab in unresponsive Systemic Lupus Erythematosis (SLE) 
Rituximab should only be prescribed by a consultant rheumatologist for eligible patients for the management of 
unresponsive SLE where standard treatment is not appropriate, not tolerated or not effective.
 
Rituximab  for Autoimmune Haemolytic Anaemia
Recommended as an alternative treatment in adults with Autoimmune Haemolytic Anaemia where patients are
contraindicated to or fail to respond to standard active treatments, such as corticosteroids.
                                                                                                                            Specialist initiation only          CCG Commissioned  

RED           Rituximab injection 100mg/10ml, 500mg/50mL 

Alemtuzumab  
RED           Alemtuzumab injection 30mg/1mL


8.2.4 Other immunomodulating drugs


RED           Interferon Alfa-2b injection pens 15mu/mL (1.2mL), 25mu/ml(1.2mL)
RED           Interferon Alfa-2a (Roferon-A®)
RED           Peginterferon Alfa-2b injection 50microgram
RED           Peginterferon Alfa-2a injection (Pegasys®)
RED           BCG (Connaught strain) bladder instillation 81mg
RED           Lenalidomide (Revlimid®) capsules 5mg, 10mg, 15mg 25mg
RED           Pomalidomide (Imnovid®) capsules  1mg, 2mg, 3mg, 4mg as an option in NICE TA427
 
 (Myelodysplasic syndromes associated with an isolated deletion 5q cytogenic abnormality (NICE TAG 322))

 (Multiple myeloma (NICE TA171)

RED           Teriflunomide (Aubagio®) tablets 14mg (NICE TA303)
RED           Thalidomide capsules 50mg
RED           Fingolimod (Gilenya®) capsules 500mcg (NICE TAG254)
                  For information about local policy variation please click <here>
RED           Mifamurtide (Mepact®) intravenous infusion 4mg
RED           Natalizumab (Tysarbri®) intravenous infusion 20mg/mL
                   For use by specialist services to treat MS
 
RED           Glatiramer acetate (Copaxone®) prefilled syringe 20mg/mL 
                   For use by specialist services to treat MS
 
RED           Dimethyl Fumarate (Tecfidara®) capsules 120mg, 240mg NICE TA320
RED           Nivolumab  intravenous infusion 10mg/mL is recommended as an option by NICE for treating advanced    
                   (unresectable or metastatic) melanoma. NICE TA384       
 
 RED            Nivolumab in combination with ipilimumab  is  recommended, within its marketing authoristaion, as an 
                   option for treating advanced (unresectable or  metastatic) melanoma in adults, only when the company

                   provides ipilimumab with the discount agreed in the patient access scheme NICE TA400                                                    

 

Beta interferons and glatiramer acetate for treating multiple sclerosis NICE TA527
(replaces NICE technology appraisal guidance 32)
 
Interferon beta-1a is recommended as an option for treating MS, only if:
           >     the person has relapsing-remitting MS and
           >     the companies provide it according to commercial arrangements.
 
Interferon beta-1b (Extavia) is recommended as an option for treating MS , only if:
          >     the person has relapsing-remitting MS and has had 2 or more relapses within the last 2 years or
          >     the person has secondary progressive MS with continuing relapses and
          >     the company provides it according to the commercial arrangement.
 
Glatiramer acetate is recommended as an option for treating MS, only if:
          >    the person has relapsing-remitting MS and
         >     the company provides it according to the commercial arrangement.
 
Interferon beta-1b (Betaferon) is not recommended within its marketing authorisation as an option for treating MS.
 
RED        Interferon beta-1a (Avonex®, Rebif®)                                                                                 (NHS England Commissioned) 
RED        Interferon beta-1b (Extavia®)                                                                                              (NHS England Commissioned)
RED        Glatiramer acetate (Copaxone®)                                                                                         (NHS England Commissioned)                                                                           

8.3.1 Oestrogens

AMBER    Diethylstilbestrol tablets 1mg
GREEN      Ethinylestradiol tablets 1mg


8.3.2 Progestogens

GREEN      Medroxyprogesterone acetate tablets 100mg, 400mg
GREEN      Megestrol acetate tablets 160mg
GREEN      Norethisterone tablets 5mg
 
For further information on the uses of Megestrol please see page 39 of guidelines <<link>> 


8.3.4 Hormone antagonists

8.3.4.1 Breast Cancer

AMBER     Anastrozole tablets 1mg
AMBER     Exemestane tablets 25mg
AMBER     Letrozole tablets 2.5mg
AMBER     Tamoxifen tablets 10mg, 20mg

8.3.4.2 Gonadorelin analogues and gonadotrophin-releasing hormone antagonists

Metastatic cancer of the prostate usually responds to hormone treatments aimed at androgen depletion. 

Gonadorelin analogues:-

Goserelin and leuprorelin are recommended for use within their licensed indications, with goserelin recommended as the first line product. Any unlicensed uses (e.g. precocious puberty) should not be transferred to primary care prescribers –prescribing should be retained by secondary care.  There are two shared care protocols in place for the use of goserelin (the preferred LHRH analogue).  One covers the use in gynaecology, the other covers the use in oncology settings (breast & prostate cancer), and they can be accessed online - click here to access them .

First Line 

AMBER with SHARED CARE     Goserelin injection 3.6mg, 10.8mg      

Second Line                                                

AMBER with SHARED CARE     Leuprorelin injection 3.75mg, 11.25mg

(currently no shared care protocols exist for the use of leuprorelin locally as it is a second line agent)

Anti-androgens:-

Anti-androgens may inhibit tumour 'flare' which may occur after adminstration of gonadorelin analogues.
 
AMBER     Generic Bicalutamide tablets 50mg, 150mg
AMBER     Cyproterone acetate tablets 50mg, 100mg
AMBER     Flutamide tablets 250mg
RED           Abiraterone Acetate tablets 250mg
RED           Enzalutamide 40mg capsules NICE TAG316 (The use of enzalutamide for treating metastatic hormone-                                relapsed prostate cancer previously treated with abiraterone is not covered by this guidance)
RED           Enzalutamide 40mg capsules recommended as an option by NICE for treating metastatic hormone relapsed 
                   prostate cancer before chemotherpay is indicated. NICE TA377 


Gonadotrophin-releasing hormone antagonists

Degarelix is a gonadotrphin-releasing hormone antagonist used to treat advanced hormone dependent prostate cancer which does not induce a testosterone surge or tumour 'flare'. Anti-androgen therapy is not required when Degarelix is used.                                                                                                                                                                                     CAMET recommends its use ONLY where LHRH analogues or concomittant anti-androgens are contra-indicated.

Degarelix is recommended as an option for treating advanced hormone-dependent prostate cancer in people with spinal metastases NICE TA404 

AMBER    Degarelix injection with diluent 80mg and 120mg          

Click here to access a Prescribing Information Sheet for Degarelix (Firmagon®)                            

8.3.4.3 Somatostatin analogues

Octreotide may be used in line with its licensed indications.  (NB - Any off license prescribing should not be passed on to primary care prescribers).

AMBER     Octreotide injection 50microgram/1ml, 1mg/5ml
AMBER     Octreotide depot injection 10mg, 20mg, 30mg


Lanreotide may be prescribed in line with its licensed indications only following recommendation from a specialist centre. (NB - Any off license prescribing should not be passed on to primary care prescribers)

AMBER      Lanreotide
                   30mg vial
                   60mg, 90mg, 120mg prefilled syringes