Bisphosphonate Guidelines for Adult Haematology and Oncology Patients

Transcription

1 Bisphosphonate Guidelines for Adult Haematology and Oncology Patients Version Two Date of Publication: June 2010 Name of responsible committee/individual: Target audience: Date of Ratification: Edited & adapted by: Dr N Jackson, Consultant Haematologist, University Hospitals Coventry and Warwickshire Carole Connor, Nurse Consultant, South Warwickshire NHS Foundation Trust Original Author(s): Dr N Jackson, Consultant Haematologist, University Hospitals Coventry and Warwickshire Arden Cancer Network Haematology Site Specific Group Haematology and Oncology Practitioners Ratified by: Arden Cancer Network Executive Group Date for Review: June 2013

2 Version History Version Date Brief Summary of Change Two June Document development to include both haematology and oncology patients 2. Updated international (ASCO) and national guidance (NICE) 3. Inclusion of Medicine and Healthcare Products Regulatory Agency advice on Bevacizumab and Sunitinib 4. Change in layout One vember 2007 First version of Network Wide document Version Two 2 of 16

3 Contents Section Page 1.0 Introduction Purpose Bisphosphonate Guidance Consultation and Communication Process Equality Impact Assessment Review and Revision Arrangements including Version Control Dissemination and Implementation References Document Circulation 10 Appendices Appendix A Appendix B Appendix C Appendix D Bisphosphonate Therapy and Dental problems. Supplementary Information for patients Bisphosphonate Therapy and Dental problems. Supplementary Information for Dentists Equality Impact Assessment Tool 15 Plan for Dissemination of Procedural Documents Version Two 3 of 16

4 1.0 Introduction Bisphosphonates are a group of drugs that have been shown to be helpful in: The treatment of hypercalcaemia of malignancy. Preventing skeletal related events and reducing pain in advanced metastatic breast cancer. Pain relief in prostate cancer. Reducing or delaying bone problems in patients with myeloma. Their mode of action is primarily adsorption onto hydroxyapatite crystals in bone thus slowing their rate of growth and dissolution hence reducing bone turnover (British National Formulary (BNF) March 2010). 2.0 Purpose This Arden Cancer Network wide document has been developed because there is a need to provide a seamless service for cancer patients across the network. This guidance does not override the individual responsibility of health professionals to make appropriate decisions according to the circumstances of the individual patient in consultation with the patient and /or carer. Health care professionals must be prepared to justify any deviation from this guidance. 3.0 Bisphosphonate Guidance 3.1 Indications The treatment of hypercalcaemia of malignancy Bisphosphonates may be helpful in inhibiting mobilisation of calcium from the skeleton (BNF 2010). The intravenous drugs of choice are usually disodium pamidronate or Zoledronic Acid. The choice of product must be discussed and agreed with the consultant haematologist/oncologist. Patients should be well hydrated prior to bisphosphonate infusions commencing. Intravenous hydration should be considered by the clinician in severe hypercalcaemia or patients unable to take oral fluids. The dose must be adjusted according to the egfr/creatinine clearance Advanced Breast Cancer Bisphosphonates should be considered for any patient newly diagnosed with bone metastases. Bisphosphonates may be helpful in managing advanced breast cancer with bone metastases to prevent skeletal-related events and reduce pain (National Institute for Health and Clinical Excellence (NICE) 2009). The recommended oral drug of choice is Ibandronic Acid 50mg daily. The recommended intravenous drug of choice is zoledronic acid. The dose must be adjusted according to the egfr/creatinine clearance (see product literature for dosing information). The dosing interval is normally every 4 weeks but the drug may be given every 3 weeks to coincide with chemotherapy. Please consult the product literature for further advice. te: The dosing interval may vary in patients enrolled in clinical trials. Version Two 4 of 16

5 3.1.3 Prostate Cancer The routine use of bisphosphonates to prevent or reduce the complications of bone metastases in men with hormone refractory prostate cancer is not recommended (NICE 2008). However, bisphosphonates for pain relief may be considered for men with hormone-refractory prostate cancer when other treatments (including analgesics and palliative radiotherapy) have failed (NICE 2008). The recommended drug of choice is zoledronic acid. The dose must be adjusted according to the egfr/creatinine clearance. The dosing interval is usually every 4 weeks. Please consult the product literature for further advice Multiple Myeloma Patients with myeloma who experience bone loss or fractures of the spine from osteopenia (lower bone density that leads to weaker bones) should receive disodium pamidronate or zoledronic acid every three to four weeks IV or oral sodium clodronate daily. The dose must be adjusted according to the egfr/creatinine clearance (see below). Bisphosphonates may be used to treat pain from bone disease. These drugs may be used along with other standard methods to relieve pain, such as radiation therapy, analgesia, or surgery for bone fractures (ASCO 2009). Bisphosphonates should also be administered to patients requiring chemotherapy with no evidence of bone lesions on plain radiographs (Nelson 2009). Bisphosphonate treatment should be given for two years but may be extended if there is evidence of active myeloma. Treatment should restart at relapse or if new bone problems develop (ASCO 2009, Terpos et al. 2009). te: Bisphosphonates are not recommended for patients with the following conditions: Solitary plasmacytoma (one bone tumour). Asymptomatic (indolent) myeloma. Clonal disorders of plasma cells that are not myeloma but may eventually develop into myeloma, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) (ASCO 2009) Management of Bone Pain Bisphosphonate therapy may be considered in patients with other malignancies for the management of severe bone pain that is not adequately managed by conventional analgesia or, where indicated, radiotherapy. The dosing interval is usually every 4 weeks. te: The recommended drug of choice is zoledronic acid for prostate and breast cancer patients or patients previously started on it as part of a clinical trial. Please consult the product literature for further advice. Version Two 5 of 16

6 3.2 Bisphosphonate Therapy Baseline Investigations/Management All patients should be given a copy of the Macmillan Cancer Support information on the specific bisphosphonate prescribed. Additionally, there are supplementary Arden Cancer Network information sheets for patients and dentists about use of bisphosphonates (Appendices A & B). All patients should be advised to have a thorough dental evaluation and corrective work undertaken before starting bisphosphonate therapy. If the agent has been started for the urgent control of hypercalcaemia, dental work should be completed within the next 3 months. Where appropriate, a bone assessment should be undertaken for example skeletal survey or bone scan. If more precise assessment is required, especially for spinal disease (which may require radiotherapy or surgery), an MRI is indicated. If no lytic bone disease is evident, then a DEXA scan may be useful to assess bone density to diagnose and/or monitor osteopenia. Baseline FBC, U&Es, calcium, phosphate and egfr/creatinine clearance (if renal function impaired) Factors to Consider when Prescribing Bisphosphonate Funding: Individual Trusts may not have all drugs listed within this guidance on their formulary. Please check prior to use and, if not, please follow internal processes to obtain approval prior to prescribing. Significant renal failure (creatinine clearance <30mL/min): avoid zoledronic acid and sodium clodronate. The clinician should consider prescribing disodium pamidronate at 30mg intravenous infusion as an alternative. In severe bone disease (lytic lesions, fracture, vertebral collapse): use a stronger bisphosphonate. Choose 1. zoledronic acid, 2. disodium pamidronate, 3. oral bisphosphonates). In myeloma patients with a longer estimated prognosis (e.g. normal Hb, normal renal function, normal albumin, low beta 2 microglobulin. Choose 1. sodium clodronate, 2. disodium pamidronate, 3. zoledronic acid. In patients with poor dental health (even if attended to), choose 1. oral bisphosphonates, 2. disodium pamidronate, 3. zoledronic acid. Patient choice The risks and benefits should be discussed with the patient. The risk of osteonecrosis of the jaw has been estimated to be 3-9 times greater with zoledronic acid than with pamidronate Oral Bisphosphonate Therapy Oral preparations licensed for use include: Ibandronic Acid 50mg daily in skeletal metastases in breast cancer. Sodium clodronate 1.6g daily in single or two divided doses increased up to a maximum of 3.2g daily. For use in osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastases in patients with breast cancer and multiple myeloma in patients who do not have impaired renal function. Version Two 6 of 16

7 3.2.4 Intravenous Bisphosphonate Therapy Intravenous preparations licensed for use include: Zoledronic acid for reduction of bone damage in advanced malignancies of the bone or as a single dose in hypercalaemia of malignancy. The standard dose is 4mg as an intravenous infusion in 100mL of sodium chloride 0.9% over 15 minutes but is progressively reduced below a creatinine clearance of 60mL/minute, and it is not used if creatinine clearance <30mL/min. Disodium pamidronate for hypercalaemia of malignancy and osteolytic lesions and bone pain in breast cancer and multiple myeloma. The dose is reduced to 30mg if the creatinine clearance <30mL/min. Each treatment of disodium pamidronate should be infused over at least 90 minutes to 2 hours (in renal impairment, a maximum of 20mg/hour), and each treatment of zoledronic acid should be infused over at least 15 minutes (ASCO 2009). The dose of bisphosphonate must be reduced in renal impairment. Please refer to product information literature for further details. 3.3 Complications Full side-effect profiles are detailed within the Summary of Product Characteristics for each drug and in the BNF Osteonecrosis of the Jaw Osteonecrosis of the jaw, an uncommon but potentially serious complication associated with the administration of intravenous bisphosphonates. Incidence of osteonecrosis of the jaw is much higher with zoledronic acid than disodium pamidronate and is more common in multiple myeloma than in other malignancies. Incidence is rare with oral bisphosphonates. Treatment with bevacizumab or sunitinib may be a risk factor for the development of osteonecrosis of the jaw, particularly if a patient has previously received, or is treated concurrently with, bisphosphonates. Dental examination and appropriate preventive dentistry should be considered before treatment with bevacizumab or sunitinib. Invasive dental procedures should be avoided, if possible, in patients treated with bevacizumab or sunitinib who have previously received, or who are receiving, intravenous bisphosphonates (Medicine and Healthcare products Regulatory Agency 2011). The majority of osteonecrosis cases occur after dental surgery, and thus a comprehensive dental examination before beginning treatment is necessary so that any dental problems that require surgical or invasive procedures can be identified and managed. Once bisphosphonate therapy has started unnecessary invasive dental procedures should be avoided and dental status should be monitored on an annual basis. If dental procedures are required during treatment, patients should be treated conservatively and invasive procedures be minimised. Postponement of bisphosphonate treatment should be considered when invasive procedures cannot be Version Two 7 of 16

8 avoided (Nelson 2009). Clinicians should consider discussing patients with a maxillofacial surgeon. Supplementary information for patients is included in appendix A and dentists Appendix B. 3.4 Patient Information All patients should be given a copy of the Macmillan Cancer Support information relating to the bisphosphonate prescribed. Additionally, there are supplementary Arden Cancer Network information sheets for patients and dentists about use of bisphosphonates (Appendices A & B). All elective patients should have a thorough dental evaluation and corrective work done before starting bisphosphonate therapy. te: it is recognised that this does not apply in the emergency treatment of hypercalaemia. Additionally, they should be advised to: Maintain good dental health & hygiene: see dentist regularly. Avoid extractions unless absolutely necessary. If extractions or extensive dental work is indicated, bisphosphonates should be withheld for at least one month before the procedure and must not be resumed until fully healed. 4.0 Consultation and Communication Process The consultation process involves dissemination of draft documents for comment to: the Arden Cancer Network Drugs and Therapeutics Committee, consultants haematologists, oncologists and haematology/oncology specialist nurses, ward managers and pharmacists at George Eliot Hospital, South Warwickshire NHS Foundation Trust, University Hospitals Coventry and Warwickshire and Worcestershire Acute Hospitals NHS Trust. 5.0 Equality Impact Assessment See Appendix C. 6.0 Review and Revision Arrangements including Version Control The Chair of the Arden Cancer Network Chemotherapy Group will nominate an individual to undertake a review of the guidance 3 months prior to the revision date. 7.0 Dissemination and Implementation Once documents are ratified, notification will be sent by to the lead chemotherapy clinician, nurse and pharmacist for each Trust. It will be their responsibility to disseminate and implement the protocol locally. The final version of documents will be placed on the Arden Cancer Network intranet and each individual Trust s intranet via a designated lead for each Trust. Hard copies will not be circulated. It will be the responsibility of departmental managers to remove outdated copies and to ensure staff are aware of the new version. It is the responsibility of departmental managers to implement any identified training or support. (Appendix D). Version Two 8 of 16

9 8.0 References American Society for Clinical Oncologists (2009) Guideline on Bisphosphonates for Multiple Myeloma, American Society for Clinical Oncologists. Barker K, Rogers S. (2006) Bisphosphonate associated osteonecrosis of the jaws: a guide for the general dental practitioner. Dental Update 33: British Medical Association and Royal Pharmaceutical Society (2010) British National Formulary 59, London, BMJ Group. Marx RE, Sawatari Y, Fortin M, Broumand V. (2005) Bisphosphonate-induced exposed bone (osteonecrosis\osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment. Journal of Oral Maxillofacial Surgery 63:1567. Medicine and Healthcare Products Regulatory Agency (2011) Bevacizumab and sunitinib: risk of osteonecrosis of the jaw. Drug Safety Update Volume 4, Issue 6 London, MHRA. Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo SB. (2005) Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper. Journal of American Dental Association. 136(12) National Institute for Health and Clinical Excellence (2009) Advanced breast cancer: diagnosis and treatment, London, NICE. National Institute for Health and Clinical Excellence (2008) Prostate cancer: diagnosis and treatment, London, NICE. Nelson R (2009) Bisphosphonates are Essential Component of Multiple Myeloma Treatment, Annals of Oncology;20: Summary of Product Characteristics for Disodium Pamidronate, Ibandronic Acid, Sodium Clodronate and Zoledronic Acid available from Terpos E, Sezer O, Croucher P et al. (2009) The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network. Annals of Oncology; 20: Version Two 9 of 16

10 9.0 Document Circulation Name Title Trust Dates Circulated Dr Jag Gandla Clinician Melanine Bowling Melanie Taylor* Stephanie Cooke Fay Lanham Sue Sharpe Ann Sullivan Dr Anton Borg Carole Connor* Nicola Evans Dr Lydia Fresco Nurse Pharmacist Pharmacist Nurse Chemotherapy Project Manager Cancer services Manager Clinician Nurse Pharmacist Clinician Dr Beth Harrison** Chair of the Haematology Network Site Specific Group George Eliot Hospitals NHS Trust Worcestershire Acute Hospitals NHS Trust South Warwickshire NHS Foundation Trust University Hospitals Coventry and Warwickshire NHS Trust Version Two 10 of 16

11 Dr Clive Irwin Chair of Arden Cancer Network Chemotherapy Group Sam Neale* Rebecca Aaron Stephanie Connell*** Nurse Chemotherapy Pharmacist Service Improvement Facilitator Arden Cancer Network *Responsible for circulating to relevant staff within their Trust including clinical nurse specialists, oncologists and ward managers. **Responsible for circulating to Haematology Network Site Specific Group Members ***Responsible for circulating to Network Chemotherapy Cross Cutting Group Version Two 11 of 16

12 Appendix A Bisphosphonate Therapy and Dental Problems Supplementary Information for Patients Bisphosphonates are a group of drugs that have been shown to be helpful in reducing or delaying bone problems in patients with some types of cancer. They may be started at diagnosis or when the first sign of bone disease appears. Currently bisphosphonates are given in tablet form (sodium clodronate and ibandronic acid) or by an intravenous infusion (disodium pamidronate and zoledronic acid). Your doctor will recommend the drug which is most suitable for your type of cancer. Once started, these drugs are usually continued for at least two years and in many cases are given long term. You will have been given a copy of a Macmillan Cancer Support leaflet on the drug you have been recommended. It tells you about the drug and summarises the main sideeffects. However, one of the side-effects is a potential dental problem. This leaflet tells how you should manage your dental care whilst on bisphosphonate therapy. You will also be given an information leaflet to give to your dentist. Jaw problems An uncommon side-effect of bisphosphonates is a condition called osteonecrosis of the jaw. This is when bone tissue in the jaw becomes damaged and dies. Gum disease, problems with your dentures and some dental treatments, such as having a tooth removed, can increase the risk of this (Macmillan Cancer Support 2010). However, it most commonly occurs after dental treatment (especially tooth extractions) or trauma to the jaw, and is a difficult condition to treat. Before starting bisphosphonate therapy: You should let your dentist know you are due to start treatment and arrange to have a full dental check up and all necessary treatment before starting on bisphosphonates. The only exception to this is if the drug has to be given for urgent control of a high blood calcium: in this case, dental work should be undertaken within 2-3 months after starting the treatment. During treatment: It is very important to look after your teeth by brushing them regularly. You should have a routine dental check-up at least yearly. If you have dental work done, please remind your dentist that you are receiving bisphosphonate therapy. Tell your dentist and cancer specialist straight away if you have pain, swelling, redness of the gums, loose teeth or a feeling of numbness or heaviness in your jaw. Version Two 12 of 16

13 Appendix B Bisphosphonate Therapy and Dental Problems Supplementary Information for Dentists Introduction Bisphosphonates are an important component of therapy in patients with myeloma and some forms of solid tumour (e.g. prostate, breast). They have been shown to reduce skeletal complications (fractures, pain). Osteonecrosis of the jaw is a serious, though unusual, complication of bisphosphonate therapy. It is often precipitated by dental work (especially extractions or major restorative work), after some years on the drug. The risk is markedly reduced if dental health is restored before starting the bisphosphonate therapy. For further information, you can contact the patient s haematologist / oncologist. An excellent review has been written by Migliorati CA et al; Journal of American Dental Association 2005;136: A brief review, by Barker & Rogers, may be found in Dental Update 2006:33; Before the patient starts bisphosphonate therapy It is recommended that patients should undergo a complete dental examination, including radiographic studies, before commencing bisphosphonates. Any necessary extractions should be completed as soon as possible. Restorative dentistry should be performed to eliminate caries and defective restorations. Pocket elimination is of importance. Once all necessary dental work has been performed and healing has taken place, the patient can return to the haematologist/oncologist to commence the bisphosphonate therapy. Advice about dental hygiene should be given to reduce plaque accumulation, and minimise chronic periodontal inflammation and the risk of acute infections. Regular follow-up visits should be planned to ensure optimal dental health, to minimise requirement for invasive work. Dental work during bisphosphonate therapy Routine restorative care may be provided, with local anaesthetic as required Scaling and polishing should be done as atraumatically as possible. Avoid extractions if possible, unless tooth very mobile. Extraction should be as atraumatic as possible, patients should be followed up weekly for 4 weeks and then monthly until complete healing has occurred. Consider use of antibiotics if infection is deemed to be present. Extensively carious teeth should be considered for endodontic therapy. They should be prepared as overdenture abutments; and the crown cut off at the gingival margin. There is no evidence that stopping the bisphosphonate before the dentistry is helpful (very long half life in bone), but some institutions are recommended a break for one months before and until full healing after major dental work. This should be Version Two 13 of 16

14 discussed individually between the haematologist/oncologist, the dentist and the patient. Any prosthetic device should fit well and may need to be re-lined with a soft liner to prevent soft tissue trauma and pressure. Effective control to a pain free state, but without resolution of the exposed bone is achieved in about 90% of cases using antibiotics and 0.12% chlorhexidine mouth wash (is this strength definitely right? Our strength is 02%) (q.i.d.) (Marx RE et al. Maxillofacial Surgery 2005;63: ) Surgery should be as conservative as possible. The aim should be only to eliminate sharp edges of protruding bone. Consider referral to a maxillofacial surgeon familiar with this problem. Although there is no evidence that stopping the bisphosphonate will aid healing, the drug will usually be discontinued to avoid further problems. Version Two 14 of 16

15 Appendix C - Equality Impact Assessment Tool 1. Does the document/guidance affect one group less or more favourably than another on the basis of: Race Ethnic origins (including gypsies and travellers) Nationality Gender Culture Religion or belief Sexual orientation including lesbian, gay and bisexual people Age Disability - learning disabilities, physical disability, sensory impairment and mental health problems 2. Is there any evidence that some groups are affected differently? 3. If you have identified potential discrimination, are there any exceptions valid, legal and/or justifiable? 4. Is the impact of the document/guidance likely to be negative? Yes/ 5. If so, can the impact be avoided? N/A 6. What alternative is there to achieving the document/guidance without the impact? 7. Can we reduce the impact by taking different action? ne Comments Version Two 15 of 16

16 Appendix D - Plan for Dissemination of Procedural Documents Title of document: Date finalised: Previous document already being used? Bisphosphonate Guidelines for Adult Haematology and Oncology Patients Yes Dissemination lead: Carole Connor Nurse Consultant South Warwickshire NHS Foundation Trust If yes, in what format and where? Guideline for Bisphosphonates in Myeloma circulated to the Haematology Network Site Specific Group Proposed action to retrieve out of date copies of the document: First Network Wide document across Haematology and Oncology. Chemotherapy lead nurse for each Trust to retrieve local documents and Haematology NSSG document To be disseminated to: How will it be disseminated, who will do it and when? Format (i.e. paper or electronic) Comments: Stephanie Connell Arden Cancer Network Karen Pedley Lead Cancer Nurse George Eliot Hospitals NHS Trust Carole Connor Nurse South Warwickshire NHS Foundation Trust To inform all areas that revised network wide electronic version available on Trusts intranet and Arden Cancer network site with 7 days of receipt Electronic Sent by Sam Neale Nurse University Hospitals Coventry and Warwickshire NHS Trust Sue Sharpe Chemotherapy Project Manager Worcestershire Acute Hospitals NHS Trust Dissemination Record - to be used once document is approved Date put on register / library of procedural documents: Date due to be reviewed: June 2013 Disseminated to: (either directly or via meetings, etc.) Format (i.e. paper or electronic) Date Disseminated:. of Copies Sent: Contact Details / Comments: Directly Electronic One Carole Connor South Warwickshire NHS Foundation Trust Version Two 16 of 16