Contents Trials. Dose guidelines. Calvert formula Issue Date: January Author: No: Copy. Pagee 1 of 21. Issue.

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1 Chapter 1: General information Contents Chapter 1: General information... 1 General observations... 2 Protocol Additions Cancer Drugs Fund... 2 Off Protocol Treatment Policy... 2 Trials... 2 Co-payments / top-ups / additional private care... 3 Dose Capping CCC anti-emetic guidelines for cytotoxic chemotherapy... 4 GCSF Primary Prophylaxis... 7 Secondary Prophylaxis... 7 Erythropoietin... 8 Intrathecal Chemotherapy... 9 Creatinine Clearance... 9 Wright Creatinine Clearance Formula... 9 Calvert formula for Carboplatin dosage Cisplatin dose guidelines Cisplatin Hydration Policy Haematological Indices Guidelines for the administrationn of chemotherapy Capecitabine - Renal function recommendations Neutropenic Sepsis Policy Platelet Transfusion Policy Hypocalcaemia Hypomagnesaemia Ifosfamide Encephalopathy and Methylene Blue Ifosfamide Renal Toxicity Folinic acid rescue for high dose methotrexate CCC Dose Rounding Policy Rationale Drugs dispensed at CCC Pagee 1 of

2 General observations There is now an electronic version of the protocol book in individual chapters c which is available on the CCC internet site. This represents the working version of the book. Paper P versions will no longer be produced. Protocol Additions 2013 Pertuzumab in breast cancer FEC1000 adjuvant in breast cancer SC Herceptin for breast cancer Carboplatin as alternative to cisplatin in a number of regimens Gemcitabine / oxaliplatin in head and neck cancer Folfirinox in pancreatic cancer Regorafenib in GIST Docetaxel for gastric cancer Cancer Drugs Fund A number of treatments are available via the National Cancer Drugs Fund. F The process for accessing the fund is detailed on the website: /ourwork/pe/ cdf/ Retrospective funding will not be available for the cost of drug treatments provided prior to the decision to fund thatt drug treatment for that patient or cohort of patients under thee CDF. The exception to this is only in cases justified as exceptionally clinically urgent and where the application is made within two working days of treatmentt and Trusts will treat at their t own financial risk until funding is confirmed. Off Protocol Treatment Policy Inevitably situations will arise that are not covered by the standard CC CC protocols. Consultants who wish to use a non-protocol regimen should complete the non-protocol treatment form and submit it to the Clinical Director for Chemotherapy for approval at least 5 days prior to the date of cycle 1 of the proposed treatment. Trials Entry to clinical trials should be considered for all patients but individual studies have not been listed due to frequent changes. Pagee 2 of

3 Co-payments / top-ups / additional private care The uptake of co-payments has been minimal and has been further reduced r by the introduction of the Cancer Drugs Fund. However the process is still in place and is outlined below. Co-payment refers to top-up funding by an NHS patient for an otherwise unavailable treatment. NHS policy allows patients to fund elements of their care not currently available on thee NHS without losing their entitlement to continue with free NHS care. The CC CC co-payments policy considers access to systemic cancer treatmentss - chemotherapy or targeted therapies - that are currently not funded for use in NHS patients. A copyy of the policy can be obtained from pharmacy or found on the CCCC website and includes all a the required documentation: Co-payment algorithm Additional Private Treatment Form Patient information leaflet. Financial agreement forms. The self-funded drug may be a single agent or given in combination with standard treatments, in which case the costs incurred relate only to the self-funded drug. However it should always be clear which components of treatment are privately funded and which are provided as NHS treatments. The patient commits to self-funding the treatment for the duration of the entire programme under supervision by the responsible consultant i. e. a specificc number of cycles or ndefinite period while there is evidence of a maintained benefit and response. This will include thee costs of treatment t preparation and delivery, payment of any investigations needed, and any supportive care drugs given as a direct consequence of receiving the self-funded treatment. Dose Capping In line with ASCO guidelines routine dose capping has been removed from the electronic prescription templates for patients with a surface area in excess of 2m 2. There are exceptions to this, and this will be detailed within the regimen, for example: Oral vinorelbine Intravenous vincristine Pagee 3 of

4 CCC anti-emetic guidelines for cytotoxic chemotherapy Oral And IV anti-emetic formulations have equivalent efficacy CCC Classification of chemotherapy by emetic potential (updated February 2012) LEVEL High Emetic Risk (>90 % frequency of emesis) AGENT Cisplatin 50mg/m² Cyclophosphamide > 1500mg/m² Dacarbazine Procarbazine (oral) Streptozocin AC Combination defined as either doxorubicin or epirubicin with cyclophosphamidee Doxorubicin >60mg/m 2 Epirubicin >90mg/ /m 2 Ifosfamide > 10g/mm 2 Moderate Emetic Risk (30-90 % frequency of emesis) Bendamustine Carboplatin Cisplatin < 50mg/ m² Cyclophosphamide 1500mg/ /m² Cyclophosphamide (oral) Dactinomycin Doxorubicin <60mg/m 2 Epirubicin <90mg/ /m 2 Etoposide (oral) Ifosfamide <10g/m 2 Interferon alpha >10million international units/mm 2 Irinotecan Lomustine Melphalan >50mg/m² Methotrexate> 2500 mg/m² Oxaliplatin Temozolomide (oral) Vinorelbine (oral) Low Emetic Risk (10-30 % frequency of emesis) Minimal Emetic Risk (<10 % frequency of emesis) Cabazitaxel Capecitabine Docetaxel Doxorubicin (Liposomal) Eribulin Etoposide (IV) Evorolimus Fludarabine (oral)) Fluorouracil Gemcitabine Alemtuzumab Alpha Interferon Bevacizumab Bleomycin Cetuximab Chlorambucil (oral) Erlotinib Fludarabine Gefitinib Imatinib (oral) Interferon alpha < <5million international units/m 2 Ipilimumab Lapatinib Interferon alpha >55 <10million international units/mm 2 Methotrexate >50mg/m² < 250mg/m² Mitomycin Mitoxantrone Nilotinib Paclitaxel Paclitaxel-albumin (Abraxane) Pemetrexed Sunitinib Topotecan Vandetanib Melphalan (oral low-dose) Methotrexate 50mg/m² Pazopanib Panitumumab Rituximab Sorafenib Rituxumab Temsirolimus Trastuzumab Vinblastine Vincristine Vinorelbine (IV) Pagee 4 of

5 Emetic Risk HIGH CISPLATIN REGIMENS Aprepitant 125mg PO day 1, 80mg PO daily days 2-3 Dexamethaso one 12mg PO/IV day 1then 4mg BD PO days 2-4 (as TTH) Ondansetron n 24mg PO or 12mg IV ( maximum 32mg see MHRA guidance) day 1 Domperidone e 10-20mg four times a day as required HIGH NOT CONTAINING CISPLATIN Dexamethaso one 12mg IV/oral PO/IV day 1 then 4mg BD PO days 2-4 (as TTH) Ondansetron n 24mg PO or 12mg IV day 1, then 8mg twice a day PO days 2-4 (seee MHRA guidance) Domperidone e 10-20mg four times a day as required Second Line Ondansetron 8mg dexamethasone 8mg Lorazepam 1mg by IV infusion over 24 hours Aprepitant 125mg PO day 1, 80mg PO daily days 2-3 Dexamethasone 12mg PO/IV day 1then 4mg twice a day PO days 2-4 (as TTH) Ondansetron 24mg PO or 12mg IV (maximum 32mg see MHRA guidance) day 1 Antiemetic Failure Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthroughh nausea and vomiting Treat on subsequent courses of chemotherapy with second line agents Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthroughh nausea and vomiting Treat on subsequent courses of chemotherapy as for second line MODERATE E Dexamethaso one 8mg PO/IV day 1 then 4mg twice a day PO days 2-4 ( as TTH) Ondansetron n 16mg PO or 8mg IV ( maximum 32mg/day seee MHRA guidance) day 1 Domperidone e 10-20mg four times a day as required LOW Dexamethaso one 8 mg PO or IV day 1 Domperidone e 10-20mg four times a day as required Aprepitant 125mg PO day 1, 80mg PO daily days 2-3 Dexamethasone 12mg PO or IV days 1-44 Ondansetron 16-24mg PO or 8-12mg IV (maximum 32mg see MHRA guidance) day 1 Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthroughh nausea and vomiting Treat on subsequent courses of chemotherapy as for high risk Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthroughh nausea and vomiting Treat on subsequent courses of chemotherapy as for moderate risk Pagee 5 of

6 MINIMAL Routine prophylaxis not always required. Domperidone e 10-20mg four times a day as required Recommend Domperidone postt chemotherapy to be taken regularly. Commence on first line antiemetics for breakthroughh nausea and vomiting Treat on subsequent courses of chemotherapy as for low risk ALTERNATIVES/BREAKTHROUGH Cyclizine 50mg threee times a day is often used for protracted nausea Prochlorperazine 5-10mg oral three times a day Prochlorperazine Suppositories 25mg three times a day Metoclopramide 10-20mg four times a day Levomepromazine 6mg at night (this can be increased to 12mg) MHRA Guidance d in July 2013 Ondansetron for intravenous use: dose-dependent QT interval prolongationn Patients age 75 years or older: A single dose of intravenous ondansetron forr the prevention of CINV must not exceed 8mg (infused over at least 15 minutes) Adult patients younger than 75 years: A single dose of intravenous ondansetron forr prevention of CINV must not exceedd 16mg (infused over at least 15 minutes) Dilution and administration in patients age 655 years or older: All intravenous doses for prevention of CINV V should be diluted in 50 or o 100mL saline and infused over at least 15 minutes In all adult patients: repeat intravenous dosess of ondansetron should be given no less than 4 hours apart Ondansetron should be avoided in patients with congenital long QT Q syndromee Caution must be used if administering ondansetron to patients with risk factors for QT interval prolongation or cardiac arrhythmias. These include: electrolyte abnormalities; use of other medicines that prolong QT interval or that may lead to electrolyte abnormalities; congestive heart failure; bradyarrhythmias; or use of medicines that lower heart rate Hypokalaemia and hypomagnesaemia should be corrected before ondansetron administration Pagee 6 of

7 GCSF Primary Prophylaxis Patients receiving FEC/Docetaxel adjuvant chemotherapy for breast cancer, EC/ /AC neoadjuvant chemotherapy for breast cancer and VIDE for STS have a high risk of o neutropenic events and in line with ASCO guidelines we recommend primary prophylaxis with pegfilgrastim 6mgg by subcutaneous injectionn 24 hours post chemotherapy. Secondary Prophylaxis In other situations where the risk of neutropenic events is lower we doo not routinely recommend primary prophylaxis with GCSF and CCC policy is that secondary prophylaxis is reserved for the t following situations: (1) To maintain dose intensity in potentially curable malignancies where the dosee limiting toxicity is neutropenia eg - Germ cell tumours - Intermediate / high grade lymphomas - Hodgkins diseasee - Sarcomas prior too potentially curative surgery - Adjuvant chemotherapy Thus if chemotherapy is delayed due to a neutropenic episode defined as either: Infection associated with neutropenia (neutrophil count < 1.0x10 9 /L) or Total WCC < 3.0x10 9 /L and neutrophil count < 1.0 x10 9 /L on the day the chemotherapy cycle was due. Then prophylaxis with pegfilgrastim 6mg s/c administered 24hrs post chemotherapy. (2) Infection associated with protracted neutropenia > 7 days There is no evidence that giving GCSF too patients with neutropenic sepsis improves outcomes in terms of survival or reduced incidence off medical sequelae. However for febrile patients with neutropenia lasting more than 7 days GCSF may be considered. Palliative Chemotherapy Pagee 7 of

8 Patients who are receiving palliative chemotherapy should be managed with appropriate dose reductions if problems with neutropenia arise. Prophylactic antibiotics The use of prophylactic antibiotics following cytotoxic chemotherapy can c result in a small reduction in febrile episodes but at the expense of side effects and the potential risk of inducing antibiotic resistance and increasing the risk of clostridium difficile infection. Thee use of prophylactic antibiotics is not therefore recommended routinely but should be reserved for patients thought to be at particularly high risk of infection. The currentt CCC protocol is: Ciprofloxacin 500mg oral BD days 9 20 post chemotherapy dependent on nadirr Erythropoietin Erythropoietin may be used to maintain haemoglobin levels during chemotherapyy in patients where transfusion is contra-indicated eg. Religious grounds Cardiac failure In addition erythropoietin may be considered in patients who have required two orr more transfusions and who are due to receive further chemotherapy. Erythropoietin may also be used to maintain haemoglobin levels during combinedd modality therapy for cervical cancer Protocol Hb > 12 no treatment required Hb < 12 darbepoetin 150micrograms / sc weekly If Hb rises to > 14 stop until Hb < 12 then restart at 100micrograms / week If Hb rises by > 2g/dL / month reduce dose too 100micrograms / week If Hb does not rise after 4 weeks treatment increase to 300micrograms / week If no response after a further weeks then stopp treatment. Pagee 8 of

9 Intrathecal Chemotherapy Department of Health regulations now dictatee that intrathecal chemotherapy may only be prepared and administered by specific named individuals. Prescriptions must be written on the intrathecal prescription form Patients must receive any IV systemic anticancer therapy prior too intrathecal treatment The doctor administering the intrathecal drugs must collect them in person from pharmacy The drugs must be checked by the doctor and a qualified chemotherapy nurse prior to administration All staff members involved (doctor, nurse, pharmacist, pharmacy technician) must be on the t current intrathecal chemotherapy register Methotrexate is the only drug we use routinely as intrathecal therapy at a flat dosee of 12.5mg. Cytarabine, thiotepa and hydrocortisone mayy also be given intrathecally. All other chemotherapy drugs are potentially lethal when administeredd intrathecally In addition any diluent used to prepare an intrathecal drug must be aqueous based and not alcohol based. Intrathecal chemotherapy must always be given under the direction of o a consultant and administered by one of the doctors on the CCCC approved list. Creatinine Clearance Wright Creatinine Clearance Formula Women Men NB Weight in kg Creatinine in micromol/l Pagee 9 of

10 Calvert formula for Carboplatin dosage Carboplatin dose in mg = AUC x (Creatinine clearance (ml/min) 25) Desired area under the curve (AUC) normallyy 4-6 depending on protocol and clinical situation Cisplatin dose guidelines Cisplatin is nephrotoxic and thus patients must have their renal function measuredd prior to each cycle. Creatinine clearance > 50mL/ /min Cisplatin dose 100% ml/min 75% < 40mL/ /min no further f cisplatin Patients should only commence cisplatinn chemotherapy if they have an adequate performance status ie 0-2. The only exception to this iss patients with advancedd germ cell tumours with poor PS who may commence treatment with low dose etoposide / platinum. Patients should only receive second and subsequent cycles of cisplatin if theyy are well and have suffered no deterioration in performance status. Pagee 10 of

11 Cisplatin Hydration Policy Cisplatin doses 20 40mg/m 2 (Outpatients) Cisplatin in 1000mL Sodium Chloride 0.9% IV over 1 hour Cisplatin doses 20 40mg/m 2 (Inpatients) Prehydration Post-hydration Sodium Chloride 0.9% 500mL Monitor urine Output Cisplatin in 1000mL Sodium Chloride 0.9% Sodium Chloride 0.9% 500mL IV over 1 hour IV over 1 hour IV over 1 hour Cisplatin doses 41-80mg/m 2 (Inpatients/Daycase) Prehydration Post-hydration Furosemide Sodium Chloride 0.9% 1000mL ( 20mmol Potassium Chloride) Monitor Urine Output Cisplatin in 1000mL Sodium Chloride 0.9% Sodium Chloride 0.9% 1000mL ( 20mmol Potassium Chloride ) PO 20mg IV over 90 minutes IV over 90 minutes IV over 90 minutes Cisplatin doses >81mg/m 2 (Inpatients) Prehydration Post-hydration Furosemide Sodium Chloride 0.9% 1000mL ( 20mmol Potassium Chloride) Monitor Urine Output Cisplatin in 1000mL Sodium Chloride 0.9% Sodium Chloride 0.9% 1000mL ( 20mmol Potassium Chloride) Sodium Chloride 0.9% 1000mL PO 20mg IV over 2 hour IV over 4 hours IV over 4 hour IV over 4 hour NB. Where urine output is of concern, or the patient experiences severe nausea and vomiting then please contact a clinician for advice. Pagee 11 of

12 Haematological Indices Guidelines for the administration of chemotherapy (1) Platelets > 100 x 10 9 /L administer Total WBC > 3 x 10 9 /L administer Neutrophils >1.0 x 10 9 /L administer (2) Platelets <100 x 10 9 /L or Total WBC < 2.9 x 10 9 /L or Neutrophils < 1.0 x 10 9 /L physician discretion physician discretion physician discretion These guidelines assume that patients are well with good performance status, that other acute toxicities have resolved and the patient has not had a previous episode of neutropenic sepsis. In some situations chemotherapy is givenn despite lower blood count values than those noted above. These include patients receiving adjuvant chemotherapy, those with curable metastatic malignancies such as germ cell tumours and lymphomas and also patients with bone marrow infiltration. Thesee situations will be dealt with on a case by case basis. b Capecitabine - Renal function f recommendations Prior to starting treatment: CrCl > 50 ml/min full dose CrCl 30 to 49 ml/min 75% dose CrCl < <30 ml/min omit During treatment if there was a rise in serum creatinine the CrCl should be re-calculated and further f treatment adjusted according to the above Pagee 12 of

13 Neutropenic Sepsis Policy Patients admitted with a fever associated with neutropenia (N < 1 x 10 9 /L) are scored according to the presence or absencee of risk factors. Age > 60yrs < 60 = 0 = 2 Dehydrated requiring iv fluids No Yes = 3 = 0 Hypotensive Systolic < <90 = 0 >90 = 5 Presence of COPD Yes No = 0 = 4 Symptoms related to infection None = 5 Mild = 5 Moderatee = 3 Severe = 0 Was the patient already in hospital Yes No = 0 = 3 Score 17 = loww risk <17= highh risk Low risk: Co-amoxiclav 625mg tds ciprofloxaxin 750mg bd or Oral doxycycline 200mg bd ciprofloxaxin 750mg bd If penicillin allergy or Ceftazidime iv 1g bolus then 2g / 24 hours continuous infusion If unable to take oral medication or already on antibiotics at home or Ceftazidime iv 1g bolus then 2g / 24 hours continuous infusion vancomycin If evidence of central line infection Pagee 13 of

14 High risk: Gentamicin piperacillin/tazobactam (Tazocin) 4.5g tds Gentamicin iv ciprofloxacin 400mg bd if penicillin allergy Add vancomycin if central line infection suspected Other pathogens Anaerobic infection suspected: metronidazole e 500mg tds Atypical respiratory infection suspected: Clarithromycin 500mg bd Platelet Transfusion Policy Platelets required if: Platelets < 10 x 10 9 / L Platelets < 100 x 10 9 /L and significant bleeding Hypocalcaemia Calcium gluconate 10% 10mL given by slow IV injection tds then switch to oral daily dose if needed ECG and calcium monitoring required Hypomagnesaemia Patients who present with symptoms suggestive of hypomagnesaemia Patients who have previously had hypomagnesaemia and who are due to have further platinum chemotherapy. Symptomatic patients with Mg <0.5 or <0.4 regardless of symptoms. Consider urgent replacement if Mg <0.4 and cardiac history (IHD, AF, AVF). If normal renal function: 40 mmol in 250 ml Sodium chloride 0.9% over 2 hours. If suspected abnormal renal function (Cr >125umol/L) or already an inpatient: 40 mmol in 1L Sodium chloride 0.9% over 8 hours. Pagee 14 of

15 Give 40 mmol and re-assess symptoms. Re-check Mg if symptoms persist or if indicated for other reasons Do not give more than 40 mmol in i one day. Ifosfamide Encephalopathy and Methylene Blue Most mild cases of ifosfamide encephalopathy will spontaneously resolve within hours. However, consider use of methylene blue if Grade 3/ Grade 4 neurotoxicity (i.e. somnolence >30% of time, disorientation/ hallucination/ echolalia/ perseveration/ coma, or seizures s on which consciousness is altered, or which are prolonged, repetitive or difficult to control). Methylene Blue 50mg IV every 6 hours. For future infusions, methylene blue 50 mg prior to infusion of ifosfamide and 50mg every 6 hours during infusion Ifosfamide Renal Toxicity Pre-treatment: Serum Early morning urine Na, K, Ca, PO 4, Cl, C total CO 2 /HCO 3, AP PO 4 Creatinine, Osmolarity O Tp/ /Creat = PO 4 serum PO 4 urine x Creat serum umol/l Creat urine GFR Tp/Creat HCO 3 Action > 60 >1.0 >17.0 Ifosfamide 100% Ifosfamide 70% < 40 <0.8 >14.0 Switch to cyclophosphamide 1500mg/m 2 IV Day 1 Pagee 15 of

16 Folinic acid rescue for high dose methotrexatee Time after starting methotrexate 24 hrs Methotrexate plasma concentration in micromol/l If serum creatinine is greater thatt 50% of normal limit, double the folinic acid dose Start folinic acid 15mg/m 2 IV every 6 hours, then follow table below < 0. 1M 0.5 5M 5 50M >50M 48 hrs Stop rescue 15mg-30mg 200mg/m mg/m 2 72 hrs Stop rescue 15mg-30mg 200mg/m mg/m 2 96 hrs Stop rescue 15mg-30mg 200mg/m mg/m hrs Stop rescue 15mg-30mg 200mg/m mg/m 2 Pagee 16 of

17 CCC Dose Rounding Policy Rationale It is widely recognised that using body surface areas (BSA) is not the most accurate method of calculating chemotherapy doses. Dose rounding does not result in a significantt dose variation from the traditional method as the maximum variation between the standard dose and the dose comprising each band is 5% or less. A range of pre-filled syringess may be used to administer the dose. This system has worked successfully in Cancer Centres in the UK 1, 2. For all intravenous chemotherapy agents there is a threshold below which itt is not possible for pharmacy to guarantee the accuracy of a given dose. This usually corresponds c to approximately 5% of a standard dose e.g. 10mg of docetaxel. Given that the calculation of chemotherapy doses on the basis of surface area iss at best an educated guess, treatment is unlikely to be compromised by rounding the dose to the nearest 5% increment. Oral agents have to be dose rounded often too a much larger tolerancee e.g. etoposide 10-16%. Dose banding has been definedd as a systemm whereby, through agreement between prescribers and pharmacists, doses of intravenous cytotoxics calculated on an individual basis, which are within defined ranges or bands are rounded up or down to predetermined standard s doses. The initial step is to decide on the bands and how best to arrive there from the calculated dose. Taking BSA to 2 decimal places and rounding the dose to thee nearest 1mL volume (taking concentration into account) appears to be the simplest way forward. easier manipulation within pharmacy. All cytotoxicc doses are rounded up/down, which allows For the following drugs the doses prescribedd should be rounded or banded b to thee indicated pharmacy tolerance level. Please note: The dose rounding information in this policy y may not cover every possible regimen. Please use your clinical judgement when rounding doses and ensure rounding does not exceed 10% of total dose. Pagee 17 of

18 Drugs dispensed at CCC Dactinomycin (Actinomycin-D)) Doses rounded to nearest 100micrograms Bevacizumab (400mg /16ml and 100mg / 4mL) Doses rounded to nearest 25mg dose Bleomycin (15000 IU Vial) Usual dose either 15,000 IU or 30,000 IU 10,000 IU/m 2 : Dosess rounded to nearest 1,000 IU Cabazitaxel Doses rounded to nearest 5mg Liposomal Doxorubicin (Caelyx ) 20mg /10mL 30mg/mm 2 : Doses rounded to nearest 2mg 40mg/mm 2 and above: Doses rounded to nearest 10mg Carboplatin 10mg/ 1mL (60mL Vial) Doses above 400mg rounded to nearest 50mg dose Doses below 400mg rounded to nearest 10mg dose Cetuximab (100mg /50mL Vial) ) BSA (m 2 ) Cetuximab (500mg/m 2 ) 700mg 800mg 900mg 1000mg CMF Regimens BSA (m 2 ) < > FU Dose 800mg 900mg 1000mg 1100mg 1200mg Methotrexate Dose 55mg 60mg 65mg 70mg 80mg Cyclophosphamide Dose 50mg TDS14/77 50mg TDS 14/ /7 50mg TDS 14/ /7 50mg TDS 14/ /7 50mg QDS 14/7 If Cyclophosphamide 50mg BD 14/7 or 50mgg QDS 14/7 required, Dr to specify onn script. Pagee 18 of

19 Cisplatin (100mg /100mL) Doses below 50mg/mm 2 : Doses rounded to nearest 5mg dose Doses 50mg/m 2 and above: Doses rounded to nearest 10mg dose Cyclophosphamide (1gram Vial) Doses below 800mg: Doses rounded to the nearest 20mg dose. Doses 800mg and above: Dosess rounded to the nearest 100mg dose. Dacarbazine (1gram Vial) Doses below 1000mg: Doses rounded to thee nearest 50mg dose. Doses 1000mg and above: Doses rounded too the nearest 100mg dose. Docetaxel (80mg Vial) Doses rounded to the nearest 20mg BSA (m 2 ) Docetaxel Dose (100mg/mm 2 ) 150mg 170mg 190mg Doxorubicin (200mg / 100mL Vial) Doses below 50mg/mm 2 : Doses rounded to nearest 2mg dose Doses 50mg/m 2 and above: Doses rounded to the nearest 10mg dose Epirubicin (50mg /25mL Vial) Doses below 50mg/mm 2 : Doses rounded to nearest 2mg dose Doses 50mg/m 2 and above: Doses rounded to the nearest 10mg dose Eribulin Doses rounded to the nearest 100micrograms Etoposide (500mg /25mL) Doses rounded to nearest 10mg dose Etopophos (Etoposide Phosphate) 100mg Vial Doses rounded to nearest 10mg dose Fluorouracil (500mg / 100mL Vial) Doses below 1000mg: Doses rounded to nearest 50mg dose Doses 1000mg and above: Doses rounded too the nearest 100mg dose Pagee 19 of

20 Fluorouracil LV5 Pumps Doses rounded to nearest 250mg dose Gemcitabine (1 gram vial) BSA below 1.4m 2 rounded to nearest 100mgg dose BSA of 1.4m 2 and above roundedd to nearest 200mg dose Irinotecan (100mg / 5mL) 20mg/mm 2 : Doses rounded to nearest 2mg dose 180mg/mm 2 and above: Doses rounded to nearest 20mg dose Ifosfamide (2 gram Vial) Doses rounded to nearest 80mg dose Ipilimumab Doses rounded to nearest 5mg dose Methotrexate (500mg / 20mL) 40mg/mm 2 and below: Doses rounded to nearest 5mg dose 1000mg/m 2 : Doses rounded to the nearest 50mg dose 1200mg/m 2 and above: Doses rounded to thee nearest 100mg dose Mesna (1000mg / 10mL) Doses rounded to nearest 100mg dose Mitomycin (10mg vial) Doses rounded to nearest 1mg dose Mitoxantrone (20mg /10mL) Doses rounded to nearest 2mg dose Oxaliplatin (100mg and 50mg Vial) 2 ) BSA (m Oxaliplatin Dose (85mg/mm 2 ) 130mg 150mg 170mg Doses below 85mg/mm 2 or BSA below 1.4m 2 : doses rounded to nearest 10mg Pagee 20 of

21 Paclitaxel (300mg / 50m, 100mg / 16.7ml, 30mg / 5mL) Doses below 180mg: Doses rounded to nearest 6mg dose Doses 180mg and above: Dosess rounded to the nearest 10mg dose Paclitaxel Albumin (Abraxane ) Doses rounded to nearest 5mg dose Pemetrexed (500mg / 20mL) Doses rounded to nearest 50mg dose Rituximab (100mg and 500mg vial) Doses rounded to nearest 10mg dose Topotecan (4mg vial) Doses rounded to nearest 100microgram dose Trastuzumab intravenous (150mg vial) Doses rounded to nearest 21mg dose Vinblastine (10mg / 10mL vial) Doses rounded to nearest 1mg dose Vincristine (2mg / 2mL) Doses rounded to nearest 100microgram dose Vindesine (5mg / 5mL) Doses rounded to nearest 1mg dose Vinorelbine (50mg / 5mL) IV: Doses rounded to nearest 5mg dose PO: Doses rounded to nearest 10mg dose Please note the dose of oral vinorelbine iss approx 2.5 times that of IV vinorelbine 25mg IV vinorelbine is approximatelyy equivalent to 60mg oral vinorelbine dose 30mg IV vinorelbine is approximatelyy equivalent to 80mg oral vinorelbine dose Plumridge R, Sewell G. Dose banding of cytotoxic drugs: A new concept in cancer chemotherapy. Am J Health Syst Pharm 2001; 58: Baker J P, Jones S E. Rationalisation of chemotherapy services at the University Hospital Birmingham NHS Trust. J Oncol Pharm Prac 1998; 4: Pagee 21 of

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