Pharmacy Guidelines for the safe use of oral anti-cancer medicines
Produced on behalf of the Greater Manchester and Cheshire Cancer Network by the Network Oncology Pharmacy Group July 2008
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Contents 1.
Introduction
2.
Individual Monographs Bexarotene Busulfan Capecitabine Chlorambucil Cyclophosphamide Dasatinib Erlotinib Etoposide Fludarabine Hydroxycarbamide Idarubicin Imatinib Lapatinib Lenalidomide Lomustine Melphalan Mercaptopurine Methotrexate Mitotane Procarbazine Sorafenib Sunitinib Tegafur/Uracil Temozolomide Thalidomide Tioguanine Treosulfan Tretinoin Vinorelbine
3.
Dose Modifications
4.
Oral Chemotherapy Regimen Summary
5.
Acknowledgements
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Introduction In January 2008 the National Patient Safety Agency (NPSA) issued a Rapid Response Report entitled ‘Risks of Incorrect Dosing of Oral Anticancer Medicines’. This report highlights the potential for fatal outcomes if incorrect doses of oral anticancer therapy are prescribed, dispensed or administered. The NPSA indicate there were at least three deaths and over four hundred patient safety incidents concerning oral anticancer therapy between November 2003 and July 2007. The principles of the chemotherapy standards in the Manual of Cancer Standards should always be applied. This covers actions required by the NPSA report and is as follows:All cancer patients receiving active anti-cancer treatment should have treatment initiated by, and be under the care of, specialist oncology/haematology staff. Local Trust chemotherapy policies and procedures must explicitly encompass oral as well as parenteral chemotherapy. All anticancer drugs, whether conventional or non-conventional cytotoxics, should be regarded as potentially hazardous, regardless of the intended route of administration. Formal risk assessment should be applied to determine for each drug the level of risk posed and hence the risk reduction and management strategy needed. The prescribing and dispensing of oral chemotherapy should be carried out and monitored to the same standards as those for parenteral chemotherapy. Responsibility for administration of oral drugs ultimately lies with the patient (or a relative or carer) but it is the responsibility of all members of the multidisciplinary oncology/haematology team to ensure as far as practically possible they are adequately prepared for this. Effective communication between primary and secondary care and with patients is pivotal to safe and effective treatment. Other than in exceptional and clearly defined and mutually agreed circumstances, prescribing and dispensing should remain the sole responsibility of the hospital-based oncologist/haematologist and pharmacy respectively. How to use this guide This document is primarily intended as a reference source for pharmacy and nursing staff to enable them to support patients receiving oral anticancer medicines. The guide covers actions required by the NPSA Rapid Response Report for the Risks of Incorrect Dosing of Oral Anticancer Medicines. Some issues are dealt with in detail in this guide, while others are documented as requiring inclusion in individual Trust Policies. Prescribing, dispensing and labelling, patient education and information, patient access to advice and support when at home, general risk management, and audit are followed by individual monographs for the oral anticancer drugs currently used within the GMCCN. There is then a section on regimens containing oral anticancer medicines. Whilst every effort has been made to ensure the accuracy of the information contained within this document, the authors accept no liability arising from its use. All personnel
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involved in the prescribing, supply or administration of anti-cancer medication should always consult the primary literature and original protocols when providing care for individual patients. The full protocol must always be consulted for full information on indications, dose, scheduling, dose modifications, drug interactions, side-effects and contra-indications. The regimen summaries do give an indication of when dose reductions may be necessary, but the Summary of Product Characteristics or British Oncology Pharmacy Association (BOPA) guidance must be consulted for specific details and clarified with the prescriber as appropriate. The document does not contain information on oral anticancer medicines that are not in use in the NHS Greater Manchester and Cheshire Cancer Network (GMCCN), i.e. medicines that do not have GMCCN D&T approval. As new medicines are approved additional drug monographs will be prepared and issued via the Network website(s). Some medicines given in the monographs may be unlicensed or used for unlicensed indications. Inclusion of individual medicines in this handbook does not imply that funding streams exist in all circumstances. For the purposes of this document the term "Oral Anticancer Medicine’ is used to refer to all drugs with direct anti-tumour activity, orally administered to cancer patients, including traditional cytotoxic chemotherapy such as capecitabine, hydroxycarbamide, chlorambucil and small molecule/ antibody treatments such as imatinib, erlotinib, sunitinib and other agents such as thalidomide or lenalidomide. It does not include hormonal or anti-hormonal agents such as tamoxifen and anastrazole. The monographs do not cover the use of oral anticancer agents in the context of clinical trials, however the basic principles contained within this document should still be applied. Guidance in this handbook is intended to promote the safe use of oral medicines used to treat cancer. Where the use of these medicines is for non-cancer treatment, a risk assessment should be undertaken and the guidance applied as appropriate. Monographs contain patient counselling points for dispensary/clinic staff. Prescribing Prescribers should have expert guidance and support at the point of prescribing. All anticancer drugs should be prescribed only in the context of written protocols. Non-specialists who prescribe or administer ongoing oral anticancer medicines should also have ready access to appropriate written protocols and treatment plans including guidance on monitoring and treatment of toxicity. The treatment plan should be documented in the notes and should include criteria for modifying and stopping treatment. Electronic systems, or prescription proformas or templates, similar to those for parenteral chemotherapy should be used. Prescriptions must state clearly for each course of treatment, the dose, frequency of administration, intended start date, duration of treatment and, where relevant, the intended stop date.
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For drugs for which a variety of schedules are in common use it is especially important that the intended schedule is unambiguously specified on every prescription. (Capecitabine, for example, may be given 2 weeks on treatment & 1 week off, 3 weeks on and 1 week off, 2 weeks on and 2 weeks off or continuously). All intended deviations from protocol, such as dose modifications, should be clearly identified as such. Without specialist advice, live vaccines should not be given to individuals with impaired immune response eg. those taking immunosuppressive drugs. Live vaccines should not be given to those being treated for malignant conditions with chemotherapy (the response to all vaccines may be reduced and there is a risk of generalised infection with live vaccines). Dispensing & labelling Prescriptions must be screened by authorised pharmacists before dispensing. All pharmacy staff who are or could be involved with dispensing oral anticancer drugs must have access to full copies of all the relevant protocols. The information available to dispensary staff must address the management of toxicity, the criteria for dose adjustments or stopping treatment, and identify circumstances and drugs in which continuous rather than intermittent treatment may be used. This applies to all treatment, both in and outwith the context of Clinical Trials Dispensary staff should work to detailed operating procedures analogous to those used for dispensing parenteral chemotherapy. Staff dispensing oral anticancer medicines should be able to confirm that the prescribed dose is appropriate for the patient, and that the patient is aware of the required monitoring arrangements, by having access to information in the written protocol and treatment plan from the hospital where treatment is initiated and advice from a pharmacist with experience in cancer treatment in that hospital. Local policy must document how specific checks, such as checking a patient’s blood results, are undertaken and recorded according to local systems of practice, as the GMCCN considers this is not necessarily the responsibility of the individual pharmacist at the time of dispensing. The format and detail of dosing instruction should be standardised and approved by an appropriate senior pharmacist. Label directions must be clear and unambiguous and include where relevant, the intended period of treatment, start and stop dates (for short term or intermittent treatment) and an appropriate indication of the need for safe handling. Whilst it is essential that all patents receive a manufacturer's PIL with their oral chemotherapy drugs the use of unbroken patient packs may also pose risks to patients if they are then given more tablets than are needed for the intended course of treatment. The decision on whether or not to issue whole packs should therefore be based on a documented local risk assessment. Manufacturers' PILs must be given (further copies can be downloaded as necessary) and may be supplemented with locally developed information and counselling points as in the following monographs. Consideration must be given to the management of patients with swallowing difficulties. Avoid breaking/crushing tablets or opening capsules whenever possible: Queries should be directed to the local pharmacy medicines information service: the advice of an oncology or technical services pharmacist must be sought. Use of a suspension or
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solution is preferred and a suitable preparation should be obtained from an NHS hospital pharmacy or commercial compounding/manufacturing facility with appropriate safehandling facilities.
Patient Education & Information Before every treatment cycle, all patients should be seen by a specialist pharmacist or nurse. The pharmacist/technician handing the drugs to the patient (or relative or carer) must ensure that they fully understand :• how and when to take their medicines. Some patients may find it particularly hard to remember the idea of repeated short courses of treatment with 'gaps' between them • what to do in the event of missing one or more doses • what to do in case of vomiting after taking a dose • likely adverse effects and what to do about them • the need for and how to obtain further supplies-only from the hospital and not the GP • the role their GP is expected to play in their treatment • principles of safe handling, storage and disposal • that if used, medicine spoons or measures should be disposable and used once only. • arrangements for monitoring • contact details for specialist advice • do not take other people’s medication and do not give your medication to others • keep the medication in the container in which it was supplied with the dispensing labels. It should be ensured that patients are informed they should not receive live vaccines while taking such medication and for a time afterwards. Specialist advice must be sought should any vaccination be required (see section on prescribing). Patients should receive verbal and written information about their oral anticancer medication from the initiating hospital, including details of the intended regimen and treatment plan, taken from the original protocol. Counselling points for individual drugs are given in the following monographs. As much of this information as possible should first be given at the pre-treatment visit and reinforced on subsequent visits. This responsibility should be confined to staff who have received training specifically for the role. When drugs are handed to the patient by non-pharmacy staff this should be the responsibility of a specialist nurse trained to the same standard.
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Patients' access to advice and support when at home Patients should be provided with details of appropriate and readily accessible 24-hour points of contact with medical, nursing and pharmacy staff to which they can direct queries. NHS cancer websites should be promoted to provide information for patients and carers at home as well as for healthcare staff. General risk management Prescribing and dispensing arrangements and procedures should take into account the Risk of wastage due to the possible need for interruption of treatment, dose modifications, inappropriate storage, loss of medicines by a patient Risk to others, especially young children, if the medicine is not safely stored in the home. Spillage of oral anticancer medicines eg. liquids should be dealt with according to the GMCCN policy for the Safe Handling of Spillages. Trusts should also consider the implications of the changes in activity type on their contract income. This will further depend on whether treatment consists of single agent oral therapy or an oral & i.v. combination regimen. Audit
All aspects of practice should be subject to regular audit Disclaimer All information given on the use of drugs in this handbook is for reference purposes only. Whilst every care has been taken to ensure accuracy of the information, it is not intended to be a comprehensive guide to using these medicines. For full information on the dosage, administration and possible adverse affects of the drugs and regimens listed we recommend that the manufacturer’s data sheets (SPC) and patient information leaflets (PILS) be consulted. www.medicine.org.uk. All drug doses are given as a guide only, chemotherapy must always be prescribed by an oncology or haematology specialist. Oral chemotherapy for solid tumours should be given in accordance with an approved patient pathway. Full Chemotherapy regimen protocols can be found on the Network websites: Acknowledgements This booklet is based on the North East Cancer Network document and thanks go to them for permission to adapt their document. All comments on contents and accuracy of document should be addressed to: Geoff Saunders, Consultant Pharmacist, Christie Hospital
Tel 0161 4463000
Email:
[email protected]
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BEXAROTENE
Information for Nursing and Pharmacy Staff: Available as: 75mg soft capsules Used for: Skin manifestations of advanced stage cutaneous T-cell lymphoma (CTCL) in patients refractory to at least one systemic treatment.
Regimens: •
CTCL: initially 300mg/m2/day continuously; can be increased up to 650mg/m2/day in individual patients. Continue treatment for as long as the patient derives benefit.
Dose modifications: Haematological: Delay treatment until counts recovered. Dose reductions for leucopenia recommended. Hepatic impairment: Dose reduction recommended in hepatic impairment (transaminases or bilirubin greater than 3 times the upper limit of normal) Renal impairment: No dose modifications recommended. Monitor patients with renal insufficiency The 300mg/m2/day dose may be reduced to 200mg/m2/day then to 100mg/m2/day or temporarily suspended if toxicity occurs. When toxicity is controlled, the dose may be carefully increased again. Emetogenic potential: Low to moderate especially in higher doses over 300mg/m2/day. Safe handling: No special requirements.
Pharmaceutical Care Issues: •
Measure fasting blood lipid levels at baseline, weekly until the lipid response of treatment is established (usually 2-4 weeks), then monthly. Fasting triglycerides should be normal before starting treatment. Antilipidaemic therapy may be required and/ or dose modification (see above).
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•
Patients with risk factors for pancreatitis should not be treated with Bexarotene.
•
LFTs should be measured at baseline, weekly for one month, then monthly. Consider suspension or discontinuation of treatment if results reach greater than three times the upper limit of normal.
•
Baseline thyroid function should be obtained, then monitored at least monthly or if symptoms of hypothyroidism emerge. Symptomatic hypothyroidism may be treated with levothyroxine. Dose modification may also be needed.
•
White blood cell counts should be obtained at baseline, weekly for one month, then monthly. If leucopoenia develops reduce the dose or discontinue Bexarotene (see above).
•
The haemoglobin level should also be measured at baseline, weekly for a month then monthly and treatment initiated if anaemia develops. Dose modifications may also need to be considered.
•
Bexarotene may enhance the action of insulin and some oral antidiabetic agents including sulphonylureas and thiazolidinediones. Monitor BMs closely and consider reducing the dose of these agents.
•
Caution in patients with known hypersensitivity to retinoids
•
Monitor patients with renal insufficiency
Drug Interactions: Bexarotene is metabolised by CYP3A4. Itraconazole, Ketoconazole, Erythromycin, Clarithromycin, Rifampicin, Dexamethasone, Phenytoin, Phenobarbital, Clozapine, Digoxin, Gemfibrozil, Protease inhibitors, Tamoxifen, Oral contraceptives.
Information for patients (counselling points): Missed dose: If you forget one dose, take your daily dose with your next meal on the same day, and then take your usual dose as normal, the following day. Do not take a double dose in one day to make up for a missed dose the previous day. Post dose vomiting: Do not take an extra capsule without consulting your doctor. Side effects: •
Low white blood cell count, anaemia
•
Thyroid disorders
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•
Hyperlipidaemia
•
Headache, fatigue, dizziness, eye disorders
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Skin reactions
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Nausea, vomiting, diarrhoea, constipation
•
Bone pain, muscle and joint aches
Storage: Room temperature. Keep the bottle tightly closed. Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines. Advice for patients: •
Capsules should be swallowed whole, not chewed.
•
Take as a single daily dose with a meal.
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Avoid grapefruit juice
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If taking vitamin A supplements limit intake to ≤ 15000 IU/day.
•
Patients should report all symptoms and signs suggestive of infection, especially sore throat.
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If dizziness or visual disturbance occurs do not drive or operate machinery. Report any visual disturbances as an eye test will be required.
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Minimise exposure to sunlight and avoid sun lamps.
•
Following administration to a man or woman conception should be avoided by using an effective contraceptive method for at least 1 month after using bexarotene. Bexarotene may decrease the efficacy of oral contraceptives therefore women should use a non-hormonal form of contraception.
•
Patients should not breast feed whilst taking Bexarotene.
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BUSULFAN Information for Nursing and Pharmacy Staff: Available as: 2mg tablets (25mg capsules are available as a special from Nova Laboratories) Used for: CML (chronic myeloid leukaemia) and as conditioning regimen prior to bone marrow transplant
Common regimens: •
CML Initial induction dose 0.06 mg/kg/day (max PO 4mg once daily) Monitor counts at least weekly and stop once response achieved.
•
CML Maintenance dose 0.5-2mg PO once daily, if daily dose less than 2mg intermittent dosing is used e.g. 2 mg twice a week.
•
Bone marrow transplant: 0.8-1 mg/kg PO every 6 hours for 4 days for a total of 16 doses; may be used in combination with other drugs
•
Myeloproliferative disorders e.g. Primary thrombocythaemia/Essential thrombocythaemia: 2-4mg PO once daily.
Note: Extremely stem cell toxic, can cause irreversible bone marrow damage if continued too long. Monitor closely for toxicity. Use with extreme caution if not familiar with use. Dosing based on body surface area or adjusted ideal body weight should be considered in the obese (see SPC).
Dose modifications: Haematological: Monitor closely for myelosuppression and reduce dose if occurs. Hepatic impairment: Consider dose reduction. Renal impairment: No adjustment necessary. Emetogenic potential: Low/non-emetogenic Safe handling: Tablets should not be divided. There is no risk in handling tablets provided outer coating on the tablets is intact.
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Pharmaceutical Care Issues: •
Discontinue if lung toxicity develops.
•
Seizures can occur with conditioning dosages-use prophylactic anticonvulsants (normally phenytoin).
Drug interactions: paracetamol, phenytoin, metronidazole, itraconazole, ketoconazole, clozapine, cyclophosphamide, tioguanine, grapefruit juice (avoid three days before and one day after busulfan)
Information for patients (counselling points): Missed dose: Do not double next dose, inform doctor and keep to normal dosing schedule. Post dose vomiting advice: Tell doctor as soon as possible; do not take an extra tablet without consulting doctor. Side effects: •
Anaemia/tiredness from bone marrow suppression
•
Hyperpigmentation
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Mucositis
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Diarrhoea
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High temperature/unexplained bruising/bleeding, contact doctor
Storage: Not above 25°C. Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines.
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CAPECITABINE
Information for Nursing and Pharmacy Staff: Available as: 150mg tablets & 500mg tablets Used for: Colorectal, Breast and Head and Neck Cancers. Please note that not all the regimens are approved.
Regimens: Gastrointestinal Tract: ECX: Capecitabine 625mg/ m2 bd on days 1-21 with epirubicin and cisplatin Repeat every 21 days. EOX: Capecitabine 625mg/ m2 bd on days 1-21 with epirubicin and oxaliplatin Repeat every 21 days. MCX: Capecitabine 625mg/m2 bd on days 1-21 with mitomycin and cisplatin Repeat every 21 days. OX-Cap / XELOX: Capecitabine 800-1000mg/m2 bd on days 1-14 with oxaliplatin Repeat every 21 days Ir-Cap: Capecitabine 1000mg/m2 bd bd on days 1-14 with irinotecan Repeat every 21 days. Single agent Capecitabine: Capecitabine 1250 mg/m2 bd on days 1-14 Repeat every 21 days. Capecitabine with XRT: Capecitabine up to 5 weeks including/excluding weekends: 825mg/m2 bd 5 weeks. There may be different dosage regimens used by different consultants. MCap: Capecitabine 625 mg/m2 bd on days 1-21 with mitomycin on alternate cycles. Repeat every 21 days.
Head and Neck: Capecitabine with XRT: Capecitabine 500mg/m2 bd including weekends start day before XRT and stop on the evening of last fraction of XRT. Cisplatin/Xeloda (XP): Capecitabine: 1000mg/ m2 bd on days 1-14 with cisplatin Repeat every 21 days.
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Breast Cancer: Single agent Capecitabine: Capecitabine 1250mg/m2 bd on days 1-14 Repeat every 21 days. Docetaxel/capecitabine: Capecitabine 1000mg/m2 bd on days 1-14 with docetaxel Repeat every 21 days. Vinorelbine/capecitabine: Capecitabine 1000mg/m2 bd on days 1-14 with vinorelbine Repeat every 21 days.
Dose modifications: Haematological: Delay treatment until counts recovered. Dose reduction recommended. Hepatic impairment: Mild to moderate hepatic impairment thought to be due to liver metastases does not warrant dose reduction. There is no information on the use of capecitabine in hepatic impairment due to other causes eg: cirrhosis. Treatment with capecitabine is contraindicated in severe hepatic impairment. Renal impairment: Mild renal impairment (CrCL >51ml/min) no dose reduction necessary. Moderate renal impairment (CrCL 30-50 ml/min) dose reduction may be necessary. Contraindicated in patients with severe renal impairment (CrCL 4 bowel movements/day or diarrhoea at night Vomiting: >once in 24 hours Nausea: loss of appetite/eating less food than normal Stomatitis: pain/redness/swelling/sores in mouth Hand-and-foot skin-reaction: pain/swelling/redness on hands and feet Fever or infection: temp >38°C or other signs
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CHLORAMBUCIL
Information for Nursing and Pharmacy Staff: Available as: 2mg tablets Used for: chronic leukaemias, lymphomas
Regimens: •
NHL: 20mg/m2 once daily for 3 days (with dexamethasone 4mg twice daily for 5 days)
•
CLL/NHL: 30mg once daily for 4 days weeks 1-4, 6, 8, 10 and 12 (prophylactic phenytoin 300mg nocte for 5 days with each cycle in patients > 60 years old starting night before first chlorambucil dose). This is a high dose regimen – always double check.
•
CLL: CLL4 trial: 10mg/m2 for 7 days every 28 days (can divide dose into 3 to reduce sickness)
•
Lymphoma: PECC: 20mg/m2 days 1-4 (with etoposide, lomustine and prednisolone)
•
Hodgkins Disease: - LOPP: 10mg daily for 1-10 days (with procarbazine and prednisolone) - ChlVPP - EVA: chlorambucil 6mg/m2 od for 7 days with procarbazine, prednisolone and etoposide repeated every 28 days for 6 cycles - CLVPP & PVACE-BOP: 6mg/m2 once daily (max 10mg) for 14 days with oral procarbazine, prednisolone (oral etoposide in PVACE-BOP)
•
Low grade Non Hodgkins Lymphoma - Patients < 70 years of age: Chlorambucil 6mg/m2 od (usually 10mg) continuously for 6 weeks initially then pulsed therapy on days 1-14 of a 28 day cycle for a further 3 months. - Patients > 70 years of age or poor performance status: Chlorambucil 6mg/m2 od (usually 10mg) on days 1-14 of a 28 day cycle for 6 cycles. (NB for patients over 80 years of age the dose may be further reduced to 6 or 8mg od)
Dose modifications
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Haematological: Because chlorambucil is capable of producing irreversible bone marrow suppression, close monitoring of full blood counts should take place for patients on this treatment Therapeutic doses of chlorambucil may reduce levels of lymphocytes, however its effects on neutrophils, platelets and haemoglobin may be less profound. It may not be necessary to discontinue treatment with chlorambucil at the first sign of a fall in neutrophils, however this fall may continue for 10 or more days after the last dose. Hepatic Impairment: Doses should be reduced if patients have gross hepatic dysfunction. The dose should be modified according to the response. Renal Impairment: No dose reduction is required, however patients should be monitored carefully as they may be more prone to myelosuppression. Emetogenic potential: Low Safe handling: Provided the outer coating of chlorambucil is intact, there is no risk in handling. Urine produced for up to 48 hours after a dose should be handled wearing protective clothing.
Pharmaceutical Care Issues: •
Only available in tablet form therefore unsuitable for patients who cannot swallow
•
Cross sensitivity with melphalan can manifest as a rash.
Drug interactions: None significant
Information for patients (counselling points): Missed dose: Do not take double next dose, inform doctor and keep to normal dosing schedule. Post dose vomiting: Tell doctor as soon as possible; do not take another tablet without consulting doctor. Side effects: •
Bone marrow suppression
•
Mouth ulcers/loss of appetite
•
Gastrointestinal disturbances (nausea/vomiting/diarrhoea)
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•
Rash – treatment should be discontinued if develops.
Storage: Refrigerate (between 2-8°C) Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines. Advice for patients: •
Not to be broken/crushed/chewed.
•
Swallow with water.
•
Tell doctor if more tired than usual, unexplained bruising/bleeding, persistent cough, weakness in muscles.
•
Refrigerate
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CYCLOPHOSPHAMIDE
Information for Nursing and Pharmacy Staff: Available as: 50mg tablets Used for: Myeloma, chronic leukaemias, lymphoma, breast, ovarian cancer
Regimens: •
Myeloma: - 500mg weekly (with dexamethasone 40mg/day on days 1-4) - 400mg/m2 weekly (with prednisolone 40mg/m2 alternate days for 6 weeks with tail off weeks 7-8). Dose reduce in renal impairment to 200mg/m2 weekly. - CTD: 500mg weekly (days 1,8,15 of 3 weekly CTD) - CTDa: 500mg weekly (days 1,8,15, 22 of 4 weekly CTD) - CVAD: 500mg days 1,8 and 15 with Dexamethasone days 1-4 and 12-15, with IV Doxorubicin 36mg/m2 days 1-4 and IV Vincristine 1.6mg days 1-4 - Weekly cyclo: 250-500mg weekly - Velcade Cyclo dex: 50mg days 1-21, with bortezomib IV 1.3mg/m2 days 1,4,8 and 11 and dexamethasone 20mg days 1, 2, 4, 5, 8, 9, 11 & 12
•
CLL: - LYOS trial (with fludarabine): 250mg/m2 from days 1-3 - CLL4 trial (with fludarabine): 150mg/m2 daily for 5 days - FC: 150mg/m2/day for 5 days (days 1-5 of 4 weekly FC)
•
Breast: CMF 100 mg/m2/day for 14 days (days 1-14 of 3 weekly CMF)
•
Ovarian: 50mg od continuously with mesna 400mg od
Note also used for non- cancer indications, e.g. vasculitis, rheumatology
Dose modifications: Haematological: Delay treatment until counts recovered. Dose reduction recommended. Hepatic impairment: Cyclophosphamide is a pro-drug that is converted by hepatic microsomal enzymes to alkylating metabolites. Manufacturer recommends dosage reduction. However, exposure to active metabolites may not be increased, suggesting that dose reduction may not be necessary. Clinical decision. Renal impairment: Cyclophosphamide is primarily renally excreted. Dose reduction is a clinical decision – consider whether patient is being treated with high dose.
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Emetogenic potential: Moderate to high dependent on dose (onset 4-12 hours, duration 4-10+ hrs) Safe handling: Pregnant or breast-feeding women should not handle tablets. Urine and faeces produced for up to 72 hours and 5 days respectively after a dose should be handled wearing protective clothing. Also present in sweat and saliva; advise caution for 72 hours after a dose when bathing the patient or carrying out oral procedures.
Pharmaceutical Care Issues: •
Report any signs of cystitis; cyclophosphamide should be avoided until treated.
•
Tablets are coated and should not be divided.
•
Antiemetics should be given before and during therapy to reduce nausea and vomiting.
Drug interactions: clozapine, warfarin, phenytoin, digoxin, chloramphenicol, pentostatin
Information for patients (counselling points): Missed dose: Take as soon as remember if it is the same day. If a days worth of tablets is missed, contact the doctor. Never take more tablets in one day than you were meant to. Do not take double next dose, inform doctor and keep to normal dosing schedule. Post dose vomiting: Tell doctor as soon as possible; do not take another tablet without consulting doctor. Anti-emetics should be given before and during therapy to reduce nausea and vomiting. Side effects: •
Nausea, vomiting
•
Hair loss/thinning (20%) within 3 weeks re-growth after 3 months of treatment
•
Headaches
•
Nail/skin colour changes
Storage: In original container less than 25°C protected from light.
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Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines. Advice for patients: •
Pregnant or breast-feeding women should not handle tablets.
•
Swallow whole preferably on an empty stomach but if gastrointestinal irritation is severe, can be taken with food.
•
Taken early in the day and plenty water through day to avoid cystitis.
•
Any sign of cystitis should be reported to doctor.
•
When in combination with fludarabine – take cyclophosphamide at breakfast and fludarabine at lunchtime.
•
All courses of cyclophosphamide will be prescribed and dispensed from the hospital. Your own GP will be informed of your treatment but should not prescribe it.
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DASATINIB
Information for Nursing and Pharmacy Staff: Available as: 20mg, 50mg and 70mg tablets Used for: Leukaemias with resistance or intolerance to prior therapy
Common regimens: •
Leukaemias: 100mg od – 100mg bd continuously (dependant on diagnosis)
Dose modifications: Haematological: Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia are recommended. Hepatic Impairment: No data available; hepatically metabolised therefore advise caution in moderate to severe hepatic impairment. Renal Impairment: No data available; 400mg in some patients) - CTD: Thalidomide 100mg once daily for 3 weeks then increasing to 200mg once daily. Taken continuously. (Combination with weekly cyclophosphamide 500mg and dexamethasone 40mg od days 1-4 and 12-15) repeated 3 weekly maximum 6 cycles. - CTDa: Thalidomide 50mg once daily for 4 weeks increasing every 4 weeks by 50mg increments to 200mg once daily (combination with cyclophosphamide 500mg weekly and dexamethasone 20mg once daily days 1-4 and 15-18). Repeated every 4 weeks maximum 9 courses (9 months) - MPT; Thalidomide 100mg once daily for 4 weeks, Melphalan 4mg/m2 days 1-7, prednisolone 40mg/m2 days 1-7. Repeated every 28 days for 6 cycles then Thalidomide 100mg once daily maintenance therapy. - DTPACE. Cislpatin 10mg/m2 daily continuous infusion days 1 to 4, Doxorubicin 10mg/m2 daily continuous infusion days 1 to 4, Cyclophosphamide 400mg/m2 days 1 to 4, Etoposide 40mg/m2 daily continuous infusion days 1 to 4, Dexamethasone 40mg once daily days 1 to 4, Thalidomide 400mg once daily continuous. -IFM 65-75yrs. Melphalan 0.25mg/kg daily days 1-4, Prednisolone 2mg/kg daily days 1-4, Thalidomide 200mg once daily for six weeks. -IFM >75yrs. Melphalan 0.18mg/kg daily days 1-4, prednisolone 2mg/kg daily days 1-4, Thalidomide 100mg once daily for six weeks.
See full protocols for details of antiinfective prophylaxis- cotrimoxazole, aciclovir, fluconazole
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Dose Modifications: Haematological: See Summary of Product Characteristics. Should not be commenced if neutrophils less than 0.75x109/L. Should be discontinued is neutrophils < 0.5x109/L. Hepatic impairment: No adjustment required. Renal impairment: No adjustment required See full protocols for advice on dose reduction for other toxicities (especially neurotoxicity) Emetogenic potential: low Safe handling: No special requirements. Pharmaceutical Care Issues: •
To supply thalidomide the pharmacy must be registered with the Pharmion Pregnancy Prevention Programme.
•
All thalidomide prescriptions must be accompanied by the appropriate documentation under the Risk Management Scheme.
•
Prescribers must read Pharmion PPP literature; patients must consent on initiation form
•
Capsule may be opened for those with problems swallowing
•
Confirm no medications are being taken which may interact with oral contraceptives to reduce their effectiveness (see BNF for details) in women taking thalidomide.
•
If these drugs must be used concurrently with thalidomide, use two other reliable methods of contraception (other than oral contraceptives).
Drug interactions: Drugs that increase risk of Venous Thromboembolism.
Information for patients (counselling points): Missed dose: Contact prescriber as soon as possible who will advise on next step to take. Do not double dose. Omit if more than eight hours after expected dosing time. Post dose vomiting: Contact prescriber as soon as possible who will advise on next step to take. Side effects:
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•
Weakness and fatigue
•
Thrombosis
•
Rash (if significant tell doctor immediately)
•
Constipation, can be relieved with senna
•
Teratogenicity
•
Cumulative peripheral neuropathy (if tingling/pain/numbness in hands or feet increases, stop taking thalidomide and tell doctor immediately)
•
Drowsiness
•
Tromor
•
bradycardia
Storage: Store at room temperature Disposal of medication: Return to hospital pharmacy to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines. Advice for patients: •
Take medication preferably one hour after meals usually at night.
•
Alcohol may enhance drowsiness caused by thalidomide. It is advised to not drink alcohol whilst taking thalidomide.
•
Drowsiness may affect driving ability. If affected do not drive or operate any tools or machinery.
•
To reduce effect of drowsiness during the day, can be taken in the evening
•
If necessary dose can be divided into two daily doses (morning and evening) – both doses should be taken at least one hour after food.
•
Do not donate blood or sperm during treatment or within one week of stopping thalidomide.
•
Breastfeeding is not recommended due to the potential secretion into breast milk.
•
Do not breast feed during treatment or start breast feeding for 4 weeks after stopping thalidomide
Information regarding pregnancy/sexual intercourse: •
Prior to treatment initiation, women of childbearing potential must have a pregnancy test immediately (e.g. within 5 days) prior to beginning therapy and regularly (e.g. monthly) during therapy. A pregnancy test is required for all women are under the age of 50 years old and who have: i.
not undergone a hysterectomy,
ii.
not been naturally postmenopausal for 24 consecutive months,
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iii.
experienced artificial menopause (e.g. chemotherapy or radiation induced menopause) or
iv. •
tubal ligation.
Women of child bearing potential must have a negative blood pregnancy test (performed by a healthcare professional): i.
Within 5 days before starting thalidomide
ii.
Every 3-4 weeks in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles while on thalidomide
iii. •
4 weeks after the last dose of thalidomide
Two methods of contraception must be used for the first 4 weeks before start taking thalidomide and continue birth control methods for the duration of treatment and for one month after stopping treatment.
•
Women must use effective contraception for at least one month before, during, and one month after thalidomide therapy.
•
Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or because patient has been naturally postmenopausal for at least 24 months.
•
To reduce the pregnancy risks on initiation of thalidomide try to start treatment within 3 days following the onset of menstrual bleeding.
•
If patient has engaged in sexual contact without using birth control thalidomide should be stopped and the doctor contacted.
•
A pregnancy test should be performed if a patient misses her period or if there is any abnormality in menstrual bleeding.
•
If a woman taking thalidomide misses a period, treatment should be stopped and the doctor informed immediately.
•
If pregnancy does occur during thalidomide therapy, thalidomide must be discontinued immediately.
•
If the female partner of a male being treated with thalidomide misses a period or has abnormal menstrual bleeding during treatment the doctor should be informed immediately.
•
Male patients should use a condom with every sexual intercourse with a female partner.
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•
If a male patient has an allergy to condoms, their female partner should use at least one very effective method of birth control. This should be started one month prior to the start of a sexual relationship and continue throughout the thalidomide treatment and for an additional month following cessation of treatment.
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TIOGUANINE (formerly known as Thiogunaine)
Information for Nursing and Pharmacy staff: Available as: 40mg tablets Used for: Acute leukaemias.
Common regimens: •
Acute leukaemias
- Standard Consolidation for patients randomised to chemotherapy in UKALL XII Version 4.0 60mg/m2 daily days 29-42. - DAT: 100mg/m2 PO BD for 5 days with Doxorubicin IV 60mg/m2 (days 1-3) and Cytarabine IV 25mg/m2 then 200mg/m2 (days 1-5) Dose Modifications: Haematological: Amend dose according to protocol. Hepatic: Liver function tests should be carried out weekly. Extensively metabolised by the liver. Consider dose reduction. The summary of product characteristics states that tioguanine should be discontinued in patients with evidence of liver toxicity. Reversal of signs and symptoms of liver toxicity have been reported upon withdrawal. Renal: Eliminated renally. Consider dose reduction.
Emetogenic potential: •
Low (if affected will occur within hours).
Safe handling: Wash hands immediately after handling/halving tablets, avoid contact with eyes and inhalation of particles. Urine and faeces produced for up to 48 hours and 5 days, respectively after a dose should be handled wearing protective clothing.
Pharmaceutical Care Issues: •
Cross resistance occurs with mercaptopurine.
•
Caution in patients with the inherited deficiency of the enzyme thiopurine methlytransferase (TMPT) who may be unusually sensitive to the
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myelosuppressive effect of tioguanine and at risk of developing rapid bone marrow depression. •
Patients with Lesch-Nyhan syndrome may be resistant to tioguanine.
•
Not recommended for maintenance or long term continuous use due to the risk of liver toxicity associated with vascular endothelail damage.
•
Tioguanine causes bone marrow suppression leading to leucopenia and thrombocytopenia. Anaemia is less common.
Drug interactions: •
Busulfan - The combined use of tioguanine and busulfan increases the risk of oesophageal varices, nodular regenerative hyperplasia of the liver and portal vein hypertension.
•
Aminosaliylate derivaties (eg. olsalazine, mesalazine, sulfasalazine) may inhibit the TMPT enzyme so should be administered with caution in those receiving tioguanine.
Information for patients (counselling points) How to take tablet: Swallow whole with plenty of water on an empty stomach. Missed dose: Do not take double next dose, inform doctor and keep to normal dosing schedule. Post dose vomiting: If you are sick just after talking the tablet let your doctor know as you may need to take another tablet. Do not take another tablet without first telling your doctor. Storage of tablets: At room temperature. Possible side effects: •
Bone marrow suppression (reversible)
•
Gastrointestinal intolerance
•
Stomatitis
•
Hepatic toxicity
•
Loss of vibration sense
•
Unsteady gait
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Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines.
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TREOSULFAN
Information for Nursing and Pharmacy staff: Available as: 250mg capsules Used for: Ovarian cancer
Regimens: •
Ovarian cancer: 250mg bd for 5 days on Monday to Friday of each week. Continued until disease progression. Dose may be reduced heavily pre-treated patients
Dose modifications: Haematological: The dose-limiting side effect of treosulfan is a myelosuppression, which is usually reversible. The leukocytes and platelets usually reach their baseline level after 28 days. Dose reduction recommended. Hepatic impairment: No information available. Clinical decision. Renal impairment: 50-60% renally excreted. Clinical decision. Emetogenic potential: low Safe handling: Providing outer layer of capsules are intact no risk in handling. Drug interactions: Non known.
Information for patients (counselling points): Missed dose: do not double up next dose, inform doctor and keep to normal dosing schedule. Post dose vomiting: Tell doctor as soon as possible, do not take extra tablet without consulting doctor. Side effects: •
Myelosuppression – dose limiting and usually reversible. It is manifested by a reduction in leukocytes and platelets and a decrease in haemoglobin.
•
Nausea and vomiting.
•
Alopecia (mild)
•
Skin pigmentation
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•
Allergic alveolitis
•
Pneumonia
•
Pulmonary fibrosis
•
Haemorrhagic cystitis
Storage: not above 25°C Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines. Advice for patients: capsules should be swallowed whole and not allowed to disintegrate within the mouth.
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TRETINOIN (ATRA) Information for Nursing and Pharmacy Staff: Available as: 10mg caps Used for: Acute promyelocytic leukaemia (APL).
Regimens: •
APL: 45mg / m2 in 2 divided doses until remission (max 90 days) dose rounded to the nearest 10mg.
•
APL maintenance: 45mg / m2 in 2 divided doses (with methotrexate and mercaptopurine)
Dose modifications: Haematological: No dose reduction Hepatic impairment: Dose reduction necessary. Renal impairment: Dose reduction necessary. Emetogenic potential: Rare Safe handling: No special requirements. Pharmaceutical Care Issues: •
Retinoic acid syndrome has been reported in up to 25% of patients treated with tretinoin. Retinoic acid syndrome is characterised by fever, dyspnoea, acute respiratory distress, pulmonary infiltrates, pleural and pericardial effusions, hypotension, oedema, weight gain, hepatic, renal and multi-organ failure.
Drug interactions: Ketoconazole, Tetracyclines, oral contraceptives, vitamin A preparations.
Information for patients (counselling points): Missed dose: Take capsules as soon as remember and inform Doctor. Do not double next dose. Post dose vomiting: Do not take another tablet without consulting doctor.
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Side effects: •
Dry skin
•
Dry mouth
•
Rash
•
Gastrointestinal disturbances (nausea, vomiting)
•
Bone pain
•
Headache
Storage: Between 10-30 °C. Protect from light. Keep the bottle tightly closed. Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines. Advice for patients: •
Dizziness / severe headache may impair driving ability.
•
Swallow whole with water / non-alcoholic drink, with food or eat shortly after taking medication.
•
Do not chew capsules.
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VINORELBINE
Information for Nursing and Pharmacy Staff: Available as: 20mg and 30mg capsules Used for: Non small cell lung cancer, metastatic breast cancer
Regimens: •
Breast cancer:
- Single agent: First cycle: 60 mg/m2 on days 1 and 8 of a 21 day cycle, increasing to 80mg/m2 on subsequent cycles depending on toxicities and response. - In combination with capecitabine: 60mg/m2 on days 1 and 8 of a 21 day cycle. •
Lung cancer
In combination with carboplatin/cisplatin: 60mg/m2 on day 1 and 8 of a 21 day cycle. (Note IV vinorelbine may be given on day 1)
Dose Modifications: Haematological: Delay treatment until counts recovered. Dose reduction recommended. Hepatic Impairment: The dose should be reduced if there is significant hepatic impairment. In patients with massive liver metastases (>75% of liver volume replaced by tumour) it is suggested that the dose is reduced by 25% and haematological parameters closely monitored. Renal Impairment: No dose adjustments appear necessary with impaired kidney function. Emetogenic potential: Low to moderate Safe handling: No special requirements. Storage: Refrigerate. Stable for up to 72 hours at room temperature.
Pharmaceutical Care Issues: •
Conversions: 80mg/m2 orally is equivalent to 30mg/m2 IV, 60mg/m2 orally is equivalent to 25mg/m2 IV
•
Maximum 160mg as a single dose.
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•
Should not be given concurrently with radiotherapy if the treatment area includes the liver.
•
Patients should usually be prescribed a 5HT3 anti-emetic about an hour before treatment to reduce the risk of vomiting the dose.
Drug Interactions: Caution with inhibitors/inducers of CYP3A4. e.g. omeprazole & fluoxetine
Information for patients (counselling points): Missed dose: If the scheduled days dosing is missed, contact the prescriber as a blood test may be needed to confirm if taking the missed dose is appropriate. It may be necessary that the patient has supervised consumption the next day but this is a local decision. Do not take double dose the next week. Post dose vomiting: In the case of vomiting within a few hours after drug intake, never repeat the administration of this dose. Absorption is not affected by early vomiting. Side effects: •
Nausea and vomiting
•
Diarrhoea
•
Anorexia
•
Stomatitis, oesophagitis
•
Neutropenia – reversible (beware of warning signs)
•
Progressive alopecia with treatment (usually mild)
•
Fatigue, muscle pain, jaw pain
Storage: Refrigerate between 2-8°C Disposal of medication: If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines. Advice for patients: •
Swallow whole with a glass of cold water. If capsule is chewed or sucked in error, rinse mouth with water or preferably a normal saline solution.
•
The liquid content of the capsule is an irritant and may cause damage if comes into contact with skin, mucosa or eyes.
•
Damaged or cut capsules should not be swallowed and should be returned to the pharmacy or to the doctor in order to be properly destroyed.
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•
If any contact occurs, immediate thorough washing with water or preferably with normal saline solution should be undertaken.
•
Food does not affect absorption but it is advised to take with a light snack to reduce gastro-intestinal upset.
•
Patient’s ability to drive or operate machinery may be affected however this is unlikely.
•
A blood test will be performed prior to each administration. The dose will then be confirmed to be taken or not (depending on local practice this dose will be given in the hospital unit or be taken by the patient at home after confirmation)
•
Refrigerate. Stable for up to 72 hours at room temperature.
•
Advise patient about the need to take an anti-emetic about an hour before taking the vinorelbine to reduce the risk of vomiting the capsules.
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Dose Modifications Drug Bexarotene Busulfan Capecitabine Chlorambucil Cyclophosphamide Dasatinib Erlotinib Etoposide Fludarabine Hydroxycarbamide Idarubicin Imatinib Lapatinib Lenalidomide Lomustine Melphalan Mercaptopurine Methotrexate Mitotane Procarbazine Sorafenib Sunitinib Tegafur/uracil Temozolomide Thalidomide Tioguanine Treosulfan Tretinoin Vinorelbine
Haematological ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
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Hepatic ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
Renal
Other / Notes
● ● ● ● ● ●
Irradiated products
● ● ● ● ● ● ● ●
Cardiac impairment Risk management
● Risk management ● ● ●
● ● ● 86
APPENDIX 1: ORAL CHEMOTHERAPY REGIMEN SUMMARY Notes • This section provides brief summary of regimens, drugs and doses only and is not intended as a substitution for full protocols. Users are advised to consult with full protocols for dose modification information. • Many of these regimens have parenteral (IV) components; the oral constituents are highlighted.
REGIMES FOR HAEMATO-ONCOLOGY Bexarotene -CTCL DRUG Bexarotene
DOSE
ROUTE
DAY/ DURATION
300-650mg/m2 od
Oral
Continuously
Busulphan: BMT may be used in combination with other drugs DRUG DOSE ROUTE Busulphan
Busulphan: CML Induction DRUG Busulphan
0.8-1mg/kg every 6 hours
Oral
for 4 days for a total of 16 doses
DOSE
ROUTE
DAY/ DURATION
0.06mg/kg od (max 4mg)
Oral
Continuously until aqequate response
ROUTE
DAY/ DURATION
Oral
Continuously
ROUTE
DAY/ DURATION
Oral
Continuously
Busulphan: CML Maintenance DRUG DAILY DOSE Busulphan
0.5-2mg od
. Busulphan: Myeloproliferative disorders DRUG DOSE Busulphan
DAY/ DURATION
2-4mg od
Chlorambucil: CLL/NHL DRUG
DOSE
ROUTE
DAY/ DURATION
Chlorambucil
30mg od
Oral
Days 1 to 4 on weeks 1, 2, 3, 4, 6, 8, 10 and 12.
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Chlorambucil: CLL4 trial repeat every 28 days DRUG DOSE Chlorambucil Chlorambucil: NHL DRUG Chlorambucil Dexamethasone
ROUTE
DAY/ DURATION
10mg/m2 od
Oral
Days 1 to 7
DOSE
ROUTE
DAY/ DURATION
Oral Oral
Days 1 to 3 Days 1 to 5
ROUTE
DAY/ DURATION
Oral
Continuously for 6 weeks then pulsed therapy on days 1 to 14 of a 28 day cycle for a further 3 months
2
20mg/m od 4mg bd
Chlorambucil: Low grade NHL < 70 years of age DRUG DOSE Chlorambucil
6mg/m2 od (usually 10mg od)
Chlorambucil: NHL > 70 years of age or poor PS repeat every 28 days for 6 cycles DRUG DOSE ROUTE DAY/ DURATION Chlorambucil
6mg/m2 od (usual dose 10mg)
ChlVPP – EVA repeat every 28 days DRUG DOSE Chlorambucil Vincristine Procarbazine Prednisolone Etoposide
Vinblastine Doxorubicin
6mg/m2 od 1.4mg/m2 90mg/m2 50mg/m2 75mg/m2 od increased to 100mg/m2 od from cycle 2 if grade 1 or less mucositis 6mg/m2 50mg/m2
CLVPP repeat every 28 days for 6 cycles DRUG DOSE Vinblastine Chlorambucil Procarbazine Prednisolone
6mg/m2 (max 10mg) 6mg/m2 od 100mg/m2 od (max 150mg od) 40mg od
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Oral
Days 1 to 14
ROUTE
DAY/ DURATION
Oral IV bolus Oral Oral Oral
Days 1 to 7 Day 1 Days 1 to 7 Days 1 t0 7 Days 1 to 5
IV bolus IV bolus
Day 8 Day 8
ROUTE
DAY/ DURATION
IV Bolus Oral Oral
Days 1 and 8 Days 1 to 14 Days 1 to 14
Oral
Days 1 to 14
88
CTD repeat every 21 days for a maximum of 6 cycles DRUG DOSE Thalidomide
Cyclophosphamide Dexamethasone
100mg od cycle 1 increasing to 200mg od from cycle 2 500mg weekly 40mg od
CTDa repeat every 28 days for a maximum of 9 cycles DRUG DOSE Thalidomide
ROUTE
DAY/ DURATION
Oral
Days 1 to 21
Oral Oral
Days 1,8 and 15 Days 1 to 4 and days 12 to 15
ROUTE
DAY/ DURATION
50mg od cycle 1 increasing by 50mg every cycle to a maximum 200mg od 500mg weekly 20mg od
Oral
Days 1 to 28
Oral Oral
Days 1,8,15 and 22 Days 1 to 4 and days 15 to 18
DOSE
ROUTE
DAY/ DURATION
9mg/m2/day total 0.4mg/m2 /day total 500mg weekly 40mg od
CIV Infusion CIV Infusion Oral Oral
Days 1 to 4 Days 1 to 4 Days 1, 8 and 15 Days 1 to 4 and days 12 to 15
DRUG
DOSE
ROUTE
DAY/ DURATION
Cyclophosphamide
200-400mg weekly
Oral
Day 1 each week
ROUTE
DAY/ DURATION
Oral Oral
Day 1 each week Days 1 to 4
Cyclophosphamide Dexamethasone
C-VAD repeat every 3 weeks DRUG Doxrubicin Vincristine Cyclophosphamide Dexamethasone
C-Weekly
Cyclophosphamide/prednisolone DRUG Cyclophosphamide Prednisolone
DOSE 2
400mg/m weekly 40mg/m2 od on alternate days for first 4 to 6 weeks then tapered off in weeks 7 and 8
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Cyclophosphamide/dexamethasone repeat fortnightly DRUG DOSE ROUTE Cyclophosphamide Dexamethasone
500mg weekly 40mg once daily Reduce to 20mg daily in elderly patients
Dasatinib DRUG
Oral Oral
DAY/ DURATION Days 1 and 8 Days 1 to 4
DOSE
ROUTE
DAY/ DURATION
100mg od - 70mg bd depending on diagnosis
Oral
Continuously
DRUG
DOSE
ROUTE
DAY/ DURATION
Cisplatin
10mg/m2/day
CIV
for days 1 to 4
Doxorubicin
10mg/m2/day
CIV
For days 1 to 4
Cyclophosphamide
400mg/m2/day
CIV
For days 1 to 4
Etoposide
40mg/m2/day
CIV
For days 1 to 4
Dexamethasone
40mg once daily
Oral
Days 1 to 4
Thalidomide
400mg once daily at night
Oral
continuously
Dasatinib
DTPACE
Etoposide: single agent Recurrent Hodgkins Lymphoma repeat every 28 days DRUG DOSE ROUTE DAY/ DURATION Etoposide
100mg od
Oral
For 7 to 14 days according to degree of myelosuppression
ROUTE
DAY/ DURATION
50-100mg od
Oral
Continuously depending on response and toxicity
DOSE
ROUTE
DAY/ DURATION
40mg/m2 od
Oral
Days 1 to 5
Etoposide: single agent Refractory leukaemia DRUG DOSE Etoposide
Fludarabine repeat every 28 days DRUG Fludarabine
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Fludarabine/cyclophosphamide: CLL4 trial repeat every 28 days DRUG DOSE ROUTE 24mg/m2 od 150mg/m2 od
Fludarabine Cyclophosphamide
Oral Oral
Fludarabine/cyclophosphamide: LYOS trial repeat every 28 days DRUG DOSE ROUTE 2
Fludarabine Cyclophosphamide FC (± R) repeat every 28 days DRUG Fludarabine Cyclophosphamide +/- Rituximab FMD repeat every 28 days DRUG Fludarabine Mitoxantrone Fludarabine Dexamethasone
Hydroxycarbamide: CML DRUG Hydroxycarbamide
DAY/ DURATION
Oral Oral
Days 1 to 3 Days 1 to 3
DOSE
ROUTE
DAY/ DURATION
Oral Oral IV infusion
Days 1 to 5 Days 1 to 5 Day 1
2
24mg/m od 150mg/m2 od 375mg/m2
DOSE 2
25mg/m 10mg/m2 40mg/m2 20mg
ROUTE
DAY/ DURATION
IV IV Oral Oral
Day 1 Day 1 Days 2 and 3 Days 1 to 5
DAY/ DURATION
500 to 6000mg daily in 2-3 divided doses
Oral
Continuously until IV chemo
DOSE
ROUTE
DAY/ DURATION
1000-2000mg/m2 daily in divided doses
Oral
Continuously until remission
ROUTE
DAY/ DURATION
Oral
Continuously dose is titrated to response
Hydroxycarbamide: CML Maintenance DRUG DOSE Hydroxycarbamide
Days 1 to 5 Days 1 to 5
40mg/m od 250mg/m2 od
Hydroxycarbamide: AML prior to IV chemotherapy DRUG DOSE ROUTE Hydroxycarbamide
DAY/ DURATION
2
500-1000mg/m daily in divided doses
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Hydroxycarbamide: Myeloproliferative disorders, sickle cell disease DRUG DOSE ROUTE DAY/ DURATION Hydroxycarbamide
Dose titrated according to response
Oral
Continuously
DOSE
ROUTE
DAY/ DURATION
Up to 20mg/m2 od
Oral
Days 1 to 3
DRUG
DOSE
ROUTE
DAY/ DURATION
Imatinib
400mg od-bd
Oral
Continuously
Idarubicin repeat every 21 days DRUG Idarubicin Imatinib
Lenalidomide/dexamethasone repeat every 28 days DRUG DOSE ROUTE
DAY/ DURATION
Lenalidomide
25mg od
Oral
Days 1 to 21
Dexamethasone
40mg od
Oral
Days 1 to 4, 9 to 12 and 17 to 20 for first 4 cycles then days 1-4 of subsequent cycles.
DOSE
ROUTE
DAY/ DURATION
10mg od
Oral
Continuously
Lenalidomide DRUG Lenalidomide
increase dose by 5mg every 28 days to a maximum of 25mg dependant on tolerability and response LOPP see ChlVPP
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Mercaptopurine: ALL protocol (adults 15-20yrs) DRUG DOSE Mercaptopurine
100mg/m2 od (max 150mg)
Mercaptopurine: ALL Maintenance DRUG DOSE Mercaptopurine
60mg/m2 od
ROUTE
DAY/ DURATION
Oral
Refer to protocol
ROUTE
DAY/ DURATION
Oral
Continuously Refer to protocol
Mercaptopurine: T-ALL DRUG Mercaptopurine
DOSE
ROUTE
DAY/ DURATION
60mg/m2 od
Oral
Weeks 4 to 7 and 9 to 16
then 75mg/m2 od
Oral
Weeks 25 to 31 and weeks 40 to 51 Refer to protocol
Methotrexate/Mercaptourine/Tretinoin: AML 15 trial Spanish treatment arm DRUG DOSE ROUTE DAY/ DURATION Methotrexate
15mg/m2 weekly
Oral
Maintenance therapy for two years
Mercaptopurine
50mg/m2 od
Oral
Days 1 to 15 Refer to protocol
Tretinoin
45mg/m2/day
Oral
Fifteen days out of every three months
NB: Methotrexate and mercaptopurine are stopped during tretinoin administration.
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Methotrexate: ALL- Refer to protocol DRUG DOSE
ROUTE
DAY/ DURATION
Methotrexate
20mg/m2 weekly
Oral
Weekly,continuously for 18 months
Mercaptopurine
75mg/m2 od
Oral
Continuously for 18 months
Vincristine
1.4mg/m2 (max 2mg)
IV bolus
Repeat every 3 months
Cytarabine
50mg
Intrathecal
Repeat every 3months
Prednisolone
60mg/m2 od
Oral
Days 1 to 5 every 3 months concomitantly with vincristine
Methotrexate: UKALL 2003 regimen refer to protocol DRUG DOSE ROUTE
DAY/ DURATION
20mg/m2 weekly
Oral
Weekly
DOSE
ROUTE
DAY/ DURATION
Methotrexate
10mg/m2 weekly
Oral
Determined by clinical response
DRUG
DOSE
ROUTE
DAY/ DURATION
Melphalan Prednisolone
7mg/m2 od 20mg bd or 40mg od
Oral Oral
Days 1 to 4 Days 1 to 5
ROUTE
DAY/ DURATION
Methotrexate Methotrexate: GVHD DRUG
MP
MPT repeat every 28 days for 6 cycles DRUG DOSE Melphalan Prednisolone
4mg/m2 od 40mg/m2
Oral Oral
Days 1 to 7 Days 1 to 7
Thalidomide
100mg od
Oral
Days 1 to 28
PECC repeat every 28 days DRUG Prednisolone Etoposide Chlorambucil Lomustine
DOSE
ROUTE
DAY/ DURATION
40mg od 200mg/m2 od 20mg/m2 od 100mg/m2 od
Oral Oral Oral Oral
Days 1 to 7 Days 1 to 3 Days 1 to 4 Day 1
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PVACE-BOP repeat every 28 days DRUG DOSE Vinblastine Etoposide Etoposide Chlorambucil Procarbazine Doxorubicin Vincristine Bleomycin Bleomycin Prednisolone
6mg/m2 (max 10mg) 100mg/m2 200mg/m2 od 6mg/m2 od 100mg/m2 od 25mg/m2 2mg 6mg/m2 6mg/m2 40mg od
ROUTE
DAY/ DURATION
IV Bolus IV Bolus Oral Oral Oral IV Bolus IV Bolus IV Bolus IV Bolus Oral
Day 1 Day 1 Days 2 and 3 Days 1 to 14 Days 1 to 14 Day 8 Day 8 Day 15 Day 22 Days 14 to 28
Thalidomide: Maintenance following MPT/ Autograft DRUG DOSE ROUTE Thalidomide Thalidomide: Myeloma DRUG Thalidomide
100mg od
Oral
DAY/ DURATION Continuously
DOSE
ROUTE
DAY/ DURATION
50-100mg od (Max 200mg od) titrated according to response
Oral
Continuously
Tioguanine: Acute leukaemias UKALL XII Consolidation phase, cycle 3 DRUG DOSE ROUTE DAY/ DURATION Tioguanine . Tioguanine: DAT DRUG
60mg/m2 od
Oral
Days 29 to 42
DOSE
ROUTE
DAY/ DURATION
2
Tioguanine
100mg/m bd
Oral
Days 1 to 5
Doxorubicin
60mg/m2
IV
Days 1 to 3
IV CIV
Loading dose followed by CIV see full protocols for details
Cytarabine
2
25mg/m 200mg/m2/day
Tioguanine: Maintenance following DAT, see full protocol DRUG DOSE ROUTE Tioguanine
200mg/m2 od
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Oral
DAY/ DURATION Days 1 to 5
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Tretinoin: APML Induction DRUG
DOSE
ROUTE
DAY/ DURATION
Tretinoin
45mg/m2 daily in 2 divided doses
Oral
until remission (max 90 days)
Tretinoin: APML Maintenance repeat every 3 months DRUG
DOSE
Tretinoin
ROUTE
DAY/ DURATION
2
Oral
Days 1 to 15
2
Daily, continuously weekly
45mg/m od
6-Mercaptopurine
90mg/m od
Oral
Methotrexate
15mg/m2 weekly
Oral
VAPEC B repeat every 7 weeks DRUG
DOSE 2
ROUTE
DAY/ DURATION Days 8, 22 and 36 Days 8, 15 , 29 and 43 For 6 weeks then taper to zero over 10 days Days 15 to 19 and days 43 to 47 Days 1 and 29 Days 8, 22 and 36
Vincristine Doxorubicin Prednisolone
1.4mg/m 35mg/m2 50mg od
IV bolus IV bolus Oral
Etoposide
100mg/m2 od
Oral
Cyclophosphamide Bleomycin
350mg/m2 10000iu/m2
IV bolus IV bolus
Velcade/Cyclo/Dex DRUG Cyclophosphamide Bortezomib Dexamethasone
DOSE
ROUTE
DAY/ DURATION
50mg od 1.3mg/m2 20mg od
Oral IV bolus Oral
Days 1 to 21 Days 1, 4, 8 and 11 Days 1, 2, 4, 5, 8, 9, 11 and 12
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VEPEMB repeat every 28 days DRUG
DOSE
ROUTE
DAY/ DURATION
Vinblastine Cyclophosphamide Procarbazine Prednisolone Etoposide Mitozantrone
6mg/m2 (max 10mg) 500mg/m2 100mg/m2 od 30mg/m2 od 60mg/m2 od 6mg/m2
IV Bolus IV Bolus Oral Oral Oral IV Bolus
Day 1 Day 1 Days 1 to 5 Days 1 to 5 Days 15 to 19 Day 15
Bleomycin
10mg/m2
IV Bolus
Day 15
VMP repeat every 6 weeks DRUG
DOSE
ROUTE
DAY/ DURATION
Melphalan Prednisolone Bortezomib
9mg/m2 od 60mg/m2 od 1.3mg/m2
Oral Oral IV bolus
Days 1 to 4 Days 1 to 4 Days 1,4,8,11,22,25,29,32
Z-DEX repeat every 3-4 weeks DRUG Idarubicin Dexamethasone
DOSE 2
10-15mg/m od 40mg od
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ROUTE
DAY/ DURATION
Oral Oral
Days 1 to 4 Days 1 to 4, 9-12, 17-20 Cycle one. Days 1 to 4 thereafter
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REGIMES FOR SOLID TUMOURS Capecitabine repeat every 21 days DRUG DOSE Capecitabine
ROUTE
DAY/ DURATION
1250mg/m2 bd
Oral
Days 1 to 14
DOSE
ROUTE
DAY/ DURATION
Oral
Up to 5 weeks including or excluding weekends
ROUTE
DAY/ DURATION
500mg/m bd
Oral
Continuously starting the day before XRT and stopping on the evening of last fraction of XRT including weekends
DOSE
ROUTE
DAY/ DURATION
80mg/m2 120mg/m2 240mg/m2 od
IV Infusion IV Infusion Oral
Day 1 Day 1 Days 2 and 3
DOSE
ROUTE
DAY/ DURATION
AUC 5 or 6 120mg/m2 240mg/m2 od
IV Infusion IV Infusion Oral
Day 1 Day 1 Days 2 and 3
DOSE
ROUTE
DAY/ DURATION
AUC 5 or 6 100mg/m2 100mg bd
IV Infusion IV Infusion Oral
Day 1 Day 1 Days 2 and 3
Capecitabine: with XRT GI DRUG Capecitabine
2
825mg/m bd Dosage may vary by consultant
Capecitabine: with XRT Head and Neck DRUG DOSE Capecitabine
2
Cis/Etop repeat every 28 days DRUG Cisplatin Etoposide Etoposide
Carbo/Etop repeat every 28 days DRUG Carboplatin Etoposide Etoposide
Carbo/Etop repeat every 21 days DRUG Carboplatin Etoposide Etoposide
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CMF repeat every 21 days DRUG Cyclophosphamide Methotrexate Fluorouracil Cyclophosphamide DRUG Cyclophosphamide
DOSE
ROUTE
DAY/ DURATION
100mg/m2 od 40mg/m2 600mg/m2
Oral IV bolus IV bolus
Days 1 to 14 Day 1 and 8 Day 1 and 8
DOSE
ROUTE
DAY/ DURATION
50mg od
Oral
Continuously
ROUTE
DAY/ DURATION
Oral IV infusion
Days 1 to 14 Day 1
ROUTE
DAY/ DURATION
50mg/m2 60mg/m2 / AUC5 625mg/m2 bd
IV Bolus IV Infusion Oral
Day 1 Day 1 Days 1 to 21
DOSE
ROUTE
DAY/ DURATION
625mg/m2 bd 130mg/m2
Oral IV infusion
Days 1 to 21 Day 1
DOSE
ROUTE
DAY/ DURATION
150mg od
Oral
Continuously
DOSE
ROUTE
DAY/ DURATION
100mg od 1000mg/m2
Oral IV infusion
Continuously Weekly: see protocol
ROUTE
DAY/ DURATION
Oral
For 7 to 21 days with a 7 to 21 day break between treatment.
Docetaxel/capecitabine repeat every 21 days DRUG DOSE Capecitabine Docetaxel
2
1000mg/m bd 75mg/m2
ECX / ECarboX repeat every 21 days DRUG DOSE Epirubicin Cisplatin / Carboplatin Capecitabine EOX repeat every 21 days DRUG Capecitabine Oxaliplatin Erlotinib DRUG Erlotinib Erlotinib/gemcitabine DRUG Erlotinib Gemcitabine
Etoposide: single agent NSGCT/Teratoma DRUG DOSE Etoposide
50-100mg od
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Etoposide: single agent Sarcoma repeat every 21 days DRUG DOSE ROUTE Etoposide
DAY/ DURATION
50mg od
Oral
Days 1 to 14
DRUG
DOSE
ROUTE
DAY/ DURATION
Imatinib
400mg od
Oral
Continuously
DOSE
ROUTE
DAY/ DURATION
1000mg/m2 bd 180mg/m2
Oral IV infusion
Days 1 to 14 Day 1
ROUTE
DAY/ DURATION
Oral Oral
Continuously Days 1 to 14
Imatinib
Ir-Cap repeat every 21 days DRUG Capecitabine Irinotecan
Lapatinib/capecitabine repeat every 21 days DRUG DOSE Lapatinib Capecitabine
1250mg od 1000mg/m2 bd
Mitotane DRUG
DOSE
ROUTE
DAY/ DURATION
Mitotane
2000-6000mg/day in 3 to 4 divided doses increased by 1000mg/day every 1 to 2 weeks up to 8000-10000mg/day as tolerated
Oral
Continuously
DOSE
ROUTE
DAY/ DURATION
2
625mg/m bd 7mg/m2
Oral IV bolus
Days 1 to 21 Day 1 of alternate cycles
DOSE
ROUTE
DAY/ DURATION
2
Days 1 to 21 Day 1 of alternate cycles Day 1
MCap repeat every 21 days DRUG Capecitabine Mitomycin
MCX repeat every 21 days DRUG Capecitabine Mitomycin
625mg/m bd 7mg/m2
Oral IV bolus
Cisplatin
60mg/m2
IV infusion
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Melphalan repeat every 6 weeks DRUG Melphalan
DOSE
ROUTE
DAY/ DURATION
10mg od
Oral
Days 1 to 5
NP DRUG
DOSE
ROUTE
DAY/ DURATION
Vinorelbine Carboplatin Vinorelbine
25-30mg/m2 (60mg max) AUC 5 or 6 60-80mg/m2 od
IV bolus IV Infusion Oral
Day 1 Day 1 Day 8
Ox-Cap repeat every 21 days DRUG Capecitabine Oxaliplatin
DOSE
ROUTE
DAY/ DURATION
800-1000mg/m2 bd 130mg/m2
Oral IV infusion
Days 1 to 14 Day 1
PCV repeat every 6 weeks DRUG
DOSE
ROUTE
DAY/ DURATION
Procarbazine
100mg/m2 od
Oral
Days 1 to 10
Lomustine
100mg/m2 od
Oral
Day 1
Vincristine
2mg
IV bolus
Day 1
Rotterdam for 1 cycle only DRUG
DOSE
ROUTE
DAY/ DURATION
Etoposide
50mg od
Oral
Days 1 to 15 and days 29 to 43
Cisplatin
50mg/m2
IV infusion
Days 1, 8, 15, 29, 26 and 43
ROUTE
DAY/ DURATION
50mg/m2 od
Oral
Days 1 to 21 until disease progression
DOSE
ROUTE
DAY/ DURATION
400mg bd
Oral
Continuous
Rotterdam Maintenance repeat every 28 days DRUG DOSE Etoposide
Sorafenib DRUG Sorafenib
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Sunitinib repeat every 6 weeks DRUG Sunitinib
DOSE
ROUTE
DAY/ DURATION
50mg od
Oral
Days 1 to 28
ROUTE
DAY/ DURATION
Tegafur/Uracil repeat every 35 days DRUG DOSE Tegafur/Uracil
100/224mg/m2 tds
Oral
Days 1 to 28
Calcium folinate
30mg tds
Oral
Days 1 to 28
Temozolamide: Glioma with XRT DRUG DOSE Temozolamide
75mg/m2 od
ROUTE
DAY/ DURATION
Oral
Days 1 to 42
Temozolamide: Glioma maintenance following XRT repeat every 28 days for 6 cycles DRUG DOSE ROUTE DAY/ DURATION Temozolamide to commence four weeks after completing the temozolomide and radiotherapy phase
150mg/m2 od
Oral
Days 1 to 5
2
Increase to 200mg/m from cycle 2 dependant on tolerance.
Temozolamide: recurrent /progressive malignant glioma repeat every 28 days DRUG DOSE ROUTE DAY/ DURATION Temzolomide
200mg/m2 od
Oral
Days 1 to 5
ROUTE
DAY/ DURATION
200mg/m2 od
Oral
Days 1 to 5
DOSE
ROUTE
DAY/ DURATION
250mg bd
Oral
For 5 days (Monday to Friday) of each week continuously
May commence at 150 mg/m2 od for cycle 1. Temozolamide: Melanoma repeat every 28 days DRUG DOSE Temozolamide Treosulfan DRUG Treosulfan
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Vinorelbine repeat every 21 days DRUG DOSE Vinorelbine
60mg/m2 od
ROUTE
DAY/ DURATION
Oral
Days 1 and 8
Increase to 80mg/m2 from cycle 2 dependant on tolerance. Vinorelbine/capecitabine repeat every 21 days DRUG DOSE 2
ROUTE
DAY/ DURATION
Capecitabine Vinorelbine
1000mg/m bd 60mg/m2 od
Oral Oral
Days 1 to 14 Days 1 and 8
XP repeat every 21 days DRUG
DOSE
ROUTE
DAY/ DURATION
Oral IV infusion
Days 1 to 14 Day 1
Capecitabine Cisplatin
2
1000mg/m bd 75mg/m2
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Acknowledgements This booklet is based on the North East Cancer Network document and thanks go to them for permission to adapt their document.
Thanks too to all the members of the Greater Manchester and Cheshire Cancer Network Oncology Pharmacy Group who very generously gave their time and commitment to this project. Particularly to: Sue Arrand Lorraine Booth Alison Darbyshire Suzanne Dowse David Kaye Elizabeth Lamerton John Landers Richard Mellor Anne O’brien Charlotte Ollerenshaw Jonathan Peacock Michelle Rowe Louise Sutton Sue Stent Kirsty Todd Steve Wardell Julie Whitehead Geoff Saunders
July 2008
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