NHS Greater Glasgow & Clyde Area Drug and Therapeutics Committee
Greater Glasgow and Clyde Medicines
Medicines Update Oncology

PostScript Oncology Issue 18, August 2012

Produced by A Branch and J Laskey, Cancer Care Pharmacists Clinical Effectiveness

To view this edition as a pdf click here

 

1. Guideline / Policy news

Nice multi-technology appraisals

Health improvement Scotland has advised that the following advice is applicable in NHS Scotland.

TA247 Lapatinib or trastuzumab in combination with an aromatase inhibitor for the first line treatment of metastatic hormone receptor positive breast cancer that over expresses HER2 

The Scottish Medicines Consortium (SMC) has previously issued guidance to NHSScotland on the use of lapatinib (768/12) and trastuzumab (386/07) in this indication. The recommendations of NICE and SMC are consistent. 

Both drugs remain non-formulary for this indication.

 

TA251 Dasatinib, nilotinib and standard dose imatinib for Chronic Myeloid Leukaemia

This NICE MTA is consistent with the previous SMC advice for imatinib and niltoinib.  The Scottish Medicines Consortium (SMC) has previously accepted imatinib (01/02) and nilotinib (709/11) for the treatment of adult patients with newly diagnosed Philadelphia-chromosome-positive CML in the chronic phase.

The SMC has not previously issued guidance to NHSScotland on the use of dasatinib, for first-line treatment in this specific indication. This NICE MTA does not recommend dasatinib for this indication.  Therefore, dasatinib is not recommended for this indication within GGC.

A new Clinical management Guideline (CMG) for CML has been approved by the Regional Prescribing Advisory Subgroup.  The new CMG incorporates this guidance and also TA241 (see PostScript Oncology issue 17).

 

West of Scotland Cancer Network (WOSCAN) Guidelines

  

Managing chemotherapy induced nausea and vomiting

This guideline has recently been updated and approved by the Regional Prescribing Advisory Subgroup and the Cancer Therapeutics Group.  There are some important changes from the previous version including the removal of domperidone due to recent safety concerns.  Staff are encouraged to familiarise themselves with the new guideline which is available at www.intranet.woscan.scot.nhs.uk.

The implications for the existing regimens on Chemocare are significant and an implementation plan is currently being discussed with the four health boards within WOSCAN.

 

Policy Updates

  

CEL 30(2012)(Revised) Guidance for the safe delivery of systemic anti-cancer therapy

In July 2012 the Scottish Government issued revised guidance on this subject.  This guidance is endorsed by the Scottish Cancer Taskforce and has been updated to reflect new knowledge, national guidelines and legislation on the safe delivery of SACT and covers all care settings including the patient’s home. 

It supersedes HDL 29 (2005) and CEL 22(2009).  This CEL provides NHS Boards with a framework for safe practice in the prescribing, preparation, administration and disposal of SACT which will minimise the risk to patients receiving SACT and protect staff from occupational exposure to cytotoxic SACT.  The scope of this document includes biological therapies and cytotoxic chemotherapy.  It covers patients of all age groups receiving SACT, including clinical trials and any route of administration except intrathecal which is covered by the extant CEL 21 (2009).   It does not include hormonal therapies.

To view the guidance visit

http://www.sehd.scot.nhs.uk/mels/CEL2012_30.pdf

 

GGC intrathecal policy

The GGC policy for intrathecal chemotherapy has recently been updated and is available on StaffNet.

This guideline has a review date of December 2014 and is approved via the GGC Cancer Therapeutics Group.  Any comments should be sent in writing to a member of the review group as listed in the policy.

To view the policy click here

 

 

2.    Medicines Safety

 

The following issues have been highlighted in recent editions of ‘Drug Safety Update’ published by the MHRA

 

Ondansetron: Risk of QT prolongation – important new intravenous dose information

The new maximum single IV dose of ondansetron for the management of chemotherapy induced nausea and vomiting (CINV) is 16mg.  This restriction follows a review of new study data, which showed that there is a greater risk of prolongation of the QT interval, a known side effect of ondansetron, when it is used at the higher doses previously authorised for CINV.

Advice for healthcare professionals:

• A single dose of intravenous ondansetron given for the management of chemotherapy-induced nausea and vomiting in adults must not exceed 16 mg (infused over at least 15 minutes)

• Ondansetron should be avoided in patients with congenital long QT syndrome.

• Caution must be used if administering ondansetron to patients with risk factors for QT interval prolongation or cardiac arrhythmias. These include: electrolyte abnormalities; use of other medicines that prolong the QT interval (including cytotoxic drugs) or may lead to electrolyte abnormalities; congestive heart failure; bradyarrhythmias; and use of medicines which lower the heart rate

• Hypokalemia and hypomagnesemia should be corrected prior to ondansetron administration

Drug Safety Update August 2012 vol 6, issue 1

It should be noted that in the West of Scotland Guidelines for CINV the maximum recommended single IV dose of ondansetron is 8mg.  Prescribers should however note that QT prolongation is a recognised side effect of ondansetron and should take note of the above MHRA advice.

.

 

Epidermal growth factor receptor (EGFR) inhibitors: serious cases of keratitis and ulcerative keratitis  

This is an update regarding reports of keratitis and ulcerative keratitis following treatment with epidermal growth factor receptor (EGFR) inhibitors for cancer, such as panitumumab (Vectibix). In rare cases, this has resulted in corneal perforation and blindness. The EGFR inhibitors, cetuximab (Erbitux), erlotinib (Tarceva▼), gefitinib (Iressa▼) and panitumumab (Vectibix▼), are used to treat EGFR-expressing tumours. 

Advice for healthcare professionals:

  • Ulcerative keratitis is an opthalmological emergency
  • Patients undergoing treatment with EGFR inhibitors who present with acute or worsening signs and symptoms suggestive of keratitis such as: eye inflammation; increased lacrimation; light sensitivity; blurred vision; eye pain and/or red eye should be referred promptly to an ophthalmology specialist
  • If a diagnosis of ulcerative keratitis is confirmed, treatment with the EGFR inhibitor should be interrupted or discontinued.
  • Patients with a history of keratitis, ulcerative keratitis or severe dry eye may be particularly at risk of ocular damage with EGFR inhibitors.

 Drug Safety Update May 2012 vol 5, issue 10

 

Safety Letter to Healthcare professionals

  

Panitumumab (Vectibix®)

A letter was sent to healthcare professionals in July regarding the association of panitumumab

(Vectibix® ) with life-threatening and fatal infectious complications of severe skin reactions including necrotising fasciitis

Panitumumab is not recommended by SMC and is non-formulary within GGC.  However, the letter can be accessed if required at www.mhra.gov.uk

 

 

SmPC Changes 

The following drugs have had recent changes to their summary of product characteristics (SmPC).  The key changes are highlighted below.  Consult the SmPC (available at www.medicines.org.uk) for full details.

 

Paclitaxel albumin (Abraxane ®) 

Section 4.4 Special warnings and precautions:Pneumonitis: Even though the incidence is low, patients should be closely monitored for signs and symptoms of pneumonitis.

 

Oxaliplatin concentrate for solution for infusion

Section 4.4 Special warnings and precautions: Information has been added about reports of Reversible Posterior Leukoencephalopathy Syndrome (RPLS) in patients receiving oxaliplatin in combination chemotherapy. Diagnosis of RPLS is based upon confirmation by brain imaging, preferably MRI (Magnetic Resonance Imaging)

Section 4.8 Undesirable effects: The following information has been added:

Very common: allergies/allergic reactions, occurring mainly during infusion, sometimes fatal. Epistaxis

Common: Febrile neutropenia, pulmonary embolism

Rare: Reversible Posterior Leukoencephalopathy syndrome, pancreatitis

The following adverse effect has been removed: Transient vision loss

 

Hydroxycarbamide (Hydrea ®) 

Section 4.4 - Special Warnings and Precautions: In patients receiving long-term therapy with hydroxycarbamide for myeloproliferative disorders, such as polycythemia, secondary leukaemia has been reported.   It is unknown whether this leukaemogenic effect is secondary to hydroxycarbamide or associated with the patients' underlying disease. Skin cancer has also been reported in patients receiving long-term hydroxyurea. Patients should be advised to protect skin from sun exposure, conduct self-inspection of the skin and be screened for secondary malignancies during routine follow-up visits.   

 

Ondansetron solution for infusion for injection

Sections 4.3 and 4.5 have been updated to include advice that concomitant use of apomorphine is contraindicated due to reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron.

 

 

3.    GGC Therapeutics Handbook 2012 – New ‘Management of oncological emergencies’ section 

The GGC Cancer Care Clinical handbook edition 1 was valid from June 2010 until June 2012 and is therefore being removed from circulation.  An updated edition is not planned and instead the GGC Therapeutics Handbook 2012, now includes a new section with advice on diagnosis and management of oncological emergencies.

The new section is entitled "Management of acute oncological emergencies" which includes. advice on:

  • malignant spinal cord compression (MSCC),
  • raised intracranial pressure
  • malignant ascites
  • tumour lysis syndrome.

In addition, within the respiratory section, there is now guidance on malignant pleural effusion, stridor and superior vena cava obstruction (SVCO).
Neutropenic sepsis is covered in the infection section, as with previous editions, and an addition to the hypercalcaemia section is a reference to the West of Scotland guidelines on the use of bisphosphonates in cancer patients.

All major changes to the GGC Therapeutics Handbook 2012 are highlighted in the latest edition of PostScript Acute, which can be found at:

www.ggcprescribing.org.uk

 

4.    Formulary and Non-formulary processes within Specialist Oncology Services

The process for addition of oncology medicines to the GGC Formulary can often seem complex and is the subject of many queries to the pharmacy department. 

There is an established process for the managed introduction of oncology medicines into GGC Formulary and this is outlined in the medicines policies section of www.ggcprescribing.org.uk

In summary, if a medicine has been approved by the Scottish Medicines Consortium this advice is considered by the West of Scotland (WOS) Regional Prescribing Advisory Subgroup who will then issue advice to local NHS boards.  This advice is accompanied by the WOS systemic anti-cancer therapy protocol.

Within GGC the Area Drugs and Therapeutics Committee consider this advice and make a decision on Formulary status.  Where the SMC have issued ‘not recommended’ advice this would then result in the medicines being non-formulary within GGC.

A special supplement of PostScript Oncology will be issued in the near future which gives more detailed advice on formulary, non-formulary and Individual Patient Treatment Request (IPTR) processes within Specialist Oncology Services.

 

5. GGC Formulary decisions

Table 1 provides an overview of GGC formulary decisions, from Feb 2012 until August 2012, relating to SMC advice / relevant NICE advice 

 

Drug

Indication

SMC / NICE advice

GGC Formulary status

azacitidine (Vidaza®)

Treatment of adult patients not eligible for haematopoietic stem cell transplant (SCT) with intermediate-2 and high risk myelodysplastic syndrome (MDS), chronic myelomoncytic leukaemia (CMML) or acute myeloid leukaemia (AML)

SMC No. 589/09 

Sep 2011 (resubmission)

Accepted for use

Added to Formulary

Restricted to use according to WOSCAN protocol which excludes the routine use in chronic myelomonocytic leukaemia (CMML). LKWOS-010/01.

erlotinib (Tarceva®)

1st line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR activating mutations

 SMC No 749/11

Jan 2012

Accepted for use

Added to Formulary

Restricted to use according to WOSCAN protocol LUWOS-029/01

imatinib (Glivec®)

Adjuvant treatment of adult patients who are at significant risk of relapse following resection of a KIT (CD117) positive gastrointestinal stromal tumour (GIST).

 SMC No 584/09

April 2012

Accepted for restricted use

Added to Formulary

Restricted to use according to WOSCAN protocol  SAWOS-003/1

mercaptopurine oral suspension (Xaluprine®)

Treatment of acute lymphoblastic leukaemia (ALL) in adults, adolescents and children.

 SMC No 798/12

Aug 2012(abbreviated submission)

Accepted for use

New formulation - added to Formulary

nilotinib (Tasigna®)

Treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukaemia (CML) in the chronic phase

 SMC No. 709/11

Aug 2011

Accepted for use

Added to Formulary

 Restricted to use according to WOSCAN protocol LKWOS-002/02

abiraterone (Zytiga®)

Use with prednisone or prednisolone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen

 SMC No. 764/12

Aug 2012(resubmission)

Accepted for restricted use

Not added to formulary pending protocol

A WOSCAN protocol has been developed and approved by the Regional Prescribing Advisory Subgroup.  The regional protocol will require approval within GGC before addition to Formulary.

everolimus (Afinitor®)

Treatment of unresectable or metastatic, well- or moderately-differentiated neuroendocrine tumours of pancreatic origin (pNET) in adults with progressive disease.

 SMC No771/12

May 2012

Accepted for use

Not added to formulary pending protocol

A WOSCAN protocol has been developed and approved by the Regional Prescribing Advisory Subgroup.  The regional protocol will require approval within GGC before addition to Formulary.

bevacizumab (Avastin®) with capecitabine

Use in combination with capecitabine as first-line treatment of patients with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. 

 SMC No 778/12

May 2012

Not recommended

Non-Formulary

catumaxomab (Removab®)

Intraperitoneal treatment of malignant ascites in patients with EpCAM-positive carcinomas where standard therapy is not available or no longer feasible.

 SMC No 788/12

April 2012

Not recommended (non-submission)

Non-Formulary

everolimus (Votubia®)

Treatment of patients aged 3 years and older with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC) who require therapeutic intervention but are not amenable to surgery

 SMC No 787/12

April 2012

Not recommended(non-submission)

Non-Formulary

ipilimumab (Yervoy®)

Treatment of advanced (unresectable or metastatic) melanoma in adults who have received prior therapy

 SMC No 779/12

May 2012

Not recommended

Non-Formulary

lapatinib (Tyverb®)

Treatment of patients with breast cancer, whose tumours overexpress HER2 (ErbB2) in combination with an aromatase inhibitor for postmenopausal women with hormone receptor positive metastatic disease, not currently intended for chemotherapy.

 SMC No 768/12

Feb 2012

Not recommended(non-submission) 

Note that this advice is superseded by but consistent with NICE MTA257

Non-Formulary

panitumumab (Vectibix®)

Treatment of patients with wild-type KRAS metastatic colorectal cancer (mCRC) in first-line in combination with FOLFOX;  in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).

 SMC No 769/12

Feb 2012

Not recommended(non-submission)

Non-Formulary

pemetrexed (Alimta®)

Monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.  

 SMC No 770/12

Feb 2012

Not recommended(non-submission)

Non-Formulary

thiotepa (Tepadina®)

In combination with other chemotherapy for conditioning prior to haematopoietic progenitor cell transplantation (HPCT) in haematological diseases or the treatment of solid tumours when high dose chemotherapy with HPCT support is appropriate.

 SMC No 790/12

August 2012

Not recommended

Non-Formulary

vandetanib (Caprelsa®)

Treatment of aggressive and symptomatic medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease

 

SMC No 797/12

June 2012

Not recommended(non-submission)

Non-Formulary

 

All WoSCAN protocols available at www.intranet.woscan.scot.nhs.uk

 

If there is anything you would like included in future issues of this bulletin please let us know.  Please direct any feedback to aly.branch@ggc.scot.nhs.uk or jennifer.laskey@ggc.scot.nhs.uk