Chemotherapy Guidelines Adelaide

7/27/2019 Chemotherapy Guidelines Adelaide

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Pain In Cancer 43

Chronic Cancer Pain 43Pleural Effusion Talc Pleurodesis Protocol 48Post-Menopausal Symptom Management 49Pruritus drug treatment 50Sperm Collection and Storage 51Symptom Control Terminal Care 53

SECTION 2

STANDARD TREATMENT POLICY GUIDELINES 56

ANAL CANCER 57BILIARY CANCER 58BLADDER (TRANSITIONAL CELL) CANCER. 59BRAIN 60BREAST CANCER 61

CERVIX CANCER 65COLORECTAL CANCER 66ENDOCRINE CANCERS 69ENDOMETRIAL CANCER 71GASTRIC CANCER 72HEAD AND NECK CANCER (SQUAMOUS CELL) 73HODGKIN'S DISEASE 74KAPOSI'S SARCOMA 75LIVER CANCER (PRIMARY) 76LUNG CANCER (SMALL CELL) 77LYMPHOMA (NON-HODGKIN'S (LOW AND HIGH GRADE) 78MELANOMA 81

MERKEL CELL TUMOUR 82

MESOTHELIOMA 83OESOPHAGEAL CANCER 84OVARIAN CANCER 85PANCREAS 86PNET TUMOURS 87RENAL CANCER 88SARCOMA 89Soft tissue 89Ewing's 90Osteogenic 90Rhabdomyosarcoma 90

SKIN CANCER (NON MELANOMA) 91TESTICULAR CANCER 92

UNKNOWN PRIMARY 94

SECTION 3

CLINICAL TRIALS95-110


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S E C T I O N O N E

G e ne ra l In fo rm a tio n

Drug Info rm a tio n

Pre v e n tio n a nd M a na g e m e nt

o f Sym p to m s/ To xic itie s


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GENERAL INFORMATION

INTRODUCTION

The Medical Oncology Treatment Policy Guidelines Booklet is divided into 3 sections. The first

contains general information such as management of toxicities and information about drugs which

require special precautions. This can be applied to many treatment situations.

The second section contains the chemotherapy regimens currently considered as standard

treatments for a variety of disease types and will be used when patients are not being entered into

clinical trials. Tumour types not listed are those where it is considered that no chemotherapy

regimen has been reported as showing sufficient benefit to be routinely offered to patients.

The final section is a listing of the chemotherapy and supportive care regimens currently being

investigated inclinical trials. Before commencing a patient on these regimens the full protocol, kept

in the wards or with the data managers or investigators, must be consulted to ensure compliance

with eligibility criteria and to obtain the full treatment details and schedules for evaluation of

efficacy and toxicity. Patients must be informed that the regimen is part of a clinical trial and

informed of the alternative management options. They must give written informed consent prior totreatment.

These guidelines will be updated regularly to ensure that the latest treatments of proven efficacy are

incorporated into standard treatments and to ensure that the listing of active clinical trials remains

current.


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PERSONNEL

CLINICAL DIRECTOR: Ian OlverOffice: Level 7 East WingPhone: 8222 5577Mobile: 0401123794Fax: 8232 2148

Email: [email protected]@mail.rah.sa.gov.au

STAFF SPECIALISTS:

Dorothy KeefeOffice: Level 7 East WingPhone: Ext. 24363Mobile: 0417861157Email: [email protected]

Anne TaylorOffice: Level 7 East WingPhone: Ext. 22023Mobile: 0401123826Email: [email protected]

Michael BrownOffice: Level 7East Wing

Phone: Ext. 22024Mobile: 0401713968Email: [email protected]

Tabitha HealeyOffice: Level 7East Wing

Phone: Ext. 24398Mobile: 0402356082Email: [email protected]

Tony MicheleCalvary Cancer Centre phone 82399242

VISITING STAFF SPECIALIST: Jack RussellRooms: 89 Payneham Road,St. Peters 5069Telephone 83625344 (rooms)Mobile: 0417227295

CLINICAL PSYCHOLOGIST: Kate MortonPhone: 8222922 (pager 22772)

Michele HurnPhone 82225626 (pager 22772)

Ward C6

Clinical Nurse Consultant Helen Kradolfer Ext 24577Ward Clerk - Pamela Bullard Ext 24574

Oncology Day Centre

CNC Judy Eden Ext 24396Day Centre ReceptionistCorinne Spearman Ext 24396

Outpatient ClinicsRegistered Nurse - Nicole Baker Ext.24406Receptionist Maria ApplekampExt.24406

SecretariesAngela Casarin Ext. 24384/25577

Margaret Collins Ext 24398

Data Managers

Medical OncologyNancy Olszewski -Page 1884, Ext. 24765Toni Marafioti - Page 22075, Ext. 24358Melinda Myers - Page 1883, Ext. 25637

DietitianDavid Cleghorn 8222 4000 (Page)

Pharmacy

Oncology Clinical Pharmacist -Jude Lees Page1507

Cytotoxic ProductionLevel 2 EW Ext 25456

Social Worker:Marie McNamee 82224000 (page)


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BLOOD PRODUCTS - ORDERING

To order blood products ring Transfusion Ext 25430.Need to know:-

blood group,

reason for platelet transfusion

platelet count.

Order irradiated products for patients where high dose therapy and a transplant is a possibility ie.lymphoma (intermediate grade and above), testicular.

CMV status should be checked prior to transplant


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PERFORMANCE STATUS - ECOG & KARNOFSKY

ECOG:

STATUS DESCRIPTION

0 Fully active, able to carry on all pre-disease performance without restriction.

1 Restricted in physically strenuous activity but ambulatory and able to carry outwork of a light sedentary nature

2 Ambulatory and capable of all self-care but unable to carry out any work. Upand about > 50% of waking hours.

3 Capable of only limited self-care, confined to bed or chair > 50% of wakinghours.

4 Completely disabled. Cannot carry out any self-care. Totally confined to bed

or chair

KARNOFSKY:

DESCRIPTION: STATUS (%)

Normal; no complaints 100

Able to carry on normal activities; minor signs or symptoms of disease 90

Normal activity with effort 80

Cares for self; unable to carry on normal activity or to do active work 70

Requires occasional assistance but able to care for most of his/her needs 60

Requires considerable assistance and frequent medical care 50

Disabled; requires special care and assistance 40

Severely disabled; hospitalisation indicated though death is not imminent 30

Very sick; hospitalisation necessary; active supportive treatment necessary 20

Moribund 10

Dead 0

Reference:Karnofsky DA, et al. Cancer 1948; 1:634-656


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SPECIAL ACCESS SCHEME

It is sometimes possible to import drugs that are not licensed in Australia for use in a specific patient.This requires:-

1. Notification of the Clinical Pharmacist (pager 1507) or the Investigational Drugs Pharmacist (Ext.25793 or mobile 0401 123 822) who will advise whether the drug is readily available, or will takesome time to arrange.

2. Completion of a Category A Form (most chemotherapy patients fulfill the criteria for Category A -Seriously ill patients with a condition from which death is reasonably likely to occur within a matterof months, or from which premature death is reasonably likely to occur in the absence of earlytreatment. The responsibility for prescribing an unapproved therapeutic good appropriately restswith the medical practitioer and the patient. It is required to obtain the patient's written consent.Category A forms are obtainable from outpatient clinics or the Pharmacy Dept. Ext 25793, or theClinical Pharmacist Pager 1507.

3. Send the completed Category A Form and a drug order including the patient s UR number to the

Pharmacy Department (marked Attention Peter Slobodian).4. If the Investigational Drugs Pharmacist advises that the patient fits Category B, which is life

threatening but not critical, the required procedure will be advised.


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VASCULAR ACCESSGuidelines For IV Access for & administration of Chemotherapy; Devices & Their Management

GUIDELINES FOR IV ACCESS & ADMINISTRATION OFCHEMOTHERAPY:

Only medical staff or senior nursing staff deemed competent are permitted to insert intravenous cannulae.

Aseptic technique must be used for insertion of all cannulae and must be secured using steri strips andprotected by nikogard for added security and easy visualisation.

Three way taps with extension tubing are placed on all IV cannulae and are changed when cannulae arereplaced as are existing IV lines.

Cannulae are to be resited every 48 hours, particularly during fluorouracil infusion to prevent/reducethrombophlebitis.

Various infusaports are an option for planned long term chemotherapy and/or poor venous access. Insertion is

done under general anaesthetic by a surgical team. Contact Mr. Gill's registrar to arrange insertion. Wherepossible ward staff should site the infusaport prior to insertion to include the patients' preferences andanatomical structures.

Infusaports can be used on the day after insertion if a needle can be inserted safely. Sutures must beremoved only after consultation with the surgical team and OPD appointments may be necessary for sutureremoval.

Only senior nursing staff having completed an accepted postgraduate oncology course or those deemedcompetent are permitted to administer bolus chemotherapy.

Extravasation kits are available from cytotoxic pharmacy and are kept routinely in the cytotoxic drug

cupboard in C6 Office. For more detailed information on drug preparation, management of spillage andextravasation see Pharmacy Manual blue pages.

DEVICES & THEIR MANAGEMENT:

Temporary Central Lines

Flush with 300u Heparin in 3mls N.Saline in each lumen.

InfusaportsFlush with 500 units Heparin in 5mls N.Saline every 3 months using Huber (non-coring) needle

To unblock an Infusaport:Use a Huber (non-coring) needle and 3 way stop cockInject Streptokinase 10,000 per ml.Turn stop cock while applying pressure so that at least 0.1-0.2 mls remains in the reservoir.Leave 30-45 mins and attempt to aspirate.If unsuccessful repeat streptokinase.

Arterial LinesFlush with 2000 units Heparin every 1-2 weeks.

PICC lines:1. Groshong lines flush with Normal Saline 10mls weekly1. Open ended lines flush with 50u Heparin in 5 mls daily


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DRUG INFORMATION

ANTHRACYCLINES

1. Cardiotoxicity

Doxorubicin, epirubicin and a related drug mitozantrone have a cumulative cardiac toxicity. It is suggested that at totaldoses of doxorubicin 450mg/m2, epirubicin 900mg/m2 and mitozantrone 120mg/m2 cardiac ejection fractions be performedbefore further doses are given, then with every alternate dose. Cardiotoxicity should be considered cumulative wheninterchanging from one anthracycline to another.

2. Dose in Liver impairment

Modify doxorubicin dose for liver impairment (Bilirubin >30). If bilirubin 30-50 give 50% dose reduction, if > 50 give 75%dose reduction.

BLEOMYCIN

1. Premedication

Hydrocortisone 100mg IV (or dexamethasone with antiemetics)2. Pulmonary fibrosisCumulative toxicity. DCO should be measured pretreatment. Patients with pulmonary dysfunction e.g. a dry cough or finecrepitations, should not be treated with bleomycin. With clinical deterioration in pulmonary function (e.g. a dry cough or finecrepitations) or a decrease in DCO, bleomycin should be stopped. A total cumulative dose of 300 units should not beexceeded.

CARBOPLATIN

DOSE CALCULATION- using Area under Concentration/Time Curve (AUC)

Initial dose of carboplatin is based on renal function:- the dose predicted to produce a defined AUC.If used as a single agent the AUC required = 7mg/ml/minIf used in combination chemotherapy the AUC required = 5mg/ml/min

To calculate total dose of carboplatin independent of body surface area use the Calvert formula:TOTAL CARBOPLATIN DOSE (mg) = target AUC x (GFR + 25)Single agent total carboplatin dose = 7 x (GFR + 25)In combinations total carboplatin dose = 5 x (GFR + 25)IfGFR is replaced by calculated creatinine clearance, decrease resulting dose by 10%

e.g.

Renal Clearance< 60ml/min calculate

yourselfml/min ml/sec

Carboplatin DoseIF renal function measured by EDTA

Mg

Carboplatin DoseIf renal function measured by

creatinine clearance(decrease by 10%)mg

60 1.0070 1.1780 1.33

90 1.50100 1.67110 1.83120 2.00

425475525

575625675725

383428473

518563608653

COCKCROFT-GAULT FORMULA FOR CALCULATING CREATININE CLEARANCE

Females:Creatinine = (140-age) x weight (in Kg)Clearance 961 x serum creatinine (in mmol/L)

Males:Creatinine = (140-age) x weight (in Kg)Clearance 814 x serum creatinine (in mmol/L)

Dosage Attenuation:

Carboplatin dose will be determined by renal function for the first cycle only. In subsequent cycles the carboplatin dose will

be determined by the platelet nadir in the previous cycle.


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PLATELET NADIR NEUTROPHIL NADIR CARBOPLATIN DOSE

> 100x109/L > 1.0x109/L Increase dose of by 10%.

50x109/L for 7 days or less notassociated with thrombocytopenicbleeding (ie Grade I and IIthrombocytopenia)

Reduce dose by 10%.

50x109/L more than 7 days or 50,associated with bleeding (ie Grade IIIor IV thrombocytopenia)

Reduce dose by 20%.

Reference:Calvert AH, Newell DR, Gumbrell, LA et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function J.

Clin Oncol 1989; 7: 1748-1756Ando Y. Minami H,Saka S, Shimokata K. Adjustment of creatinine clearance improves accuracy of Calvert`s formula for carboplatin

dosing. British Journal of Cancer 76(8):1067-71,1997

CISPLATIN

1. Renal Effects

Cisplatin is nephrotoxic and prior to the initial therapy the creatinine clearance should be calculated and renal functionmonitored prior to each course.

Magnesium (see Hypomagnesaemia page 37, Magnesium Replacement Protocol) and potassium levels should be monitoredfrequently as renal loss of both of these may occur. These should be checked with restaging.

Avoid giving other nephrotoxic drugs concomitantly with cisplatin, particularly aminoglycosides. If gentamicin must begiven, use RAH dosage guidelines (see page 39) according to renal function, and monitor serum levels.

To avoid nephrotoxicity, pre and post cisplatin hydration is given.RAH Infusion Therapy Charts have been prepared for several cisplatin regimens:

(1) Standard:Normal saline 2000mls over 2 hours, with MANNITOL 20%, 200mls over hour. Cisplatin is givenin 1 litre over 2 hours then 1 litre N.Saline over 4,6, and 8 hours (with potassium and magnesium addedas necessary).

(2) CNS regimen (using smaller volumes of 5% glucose).(3) For Cisplatin/5-FU(4) For Cisplatin/Etoposide 100mg/m2(5) For Cisplatin 5 day outpatient schedule

Prehydrate with N saline 1000mls over 2 hours. Cisplatin is given in 1 litre over 2 hours. Noposthydration is necessary if the patient is drinking adequately.

(6) For Vinblastine/Cisplatin/Ifosfamide(7) For Etoposide/Cisplatin/Ifosfamide(8) For Ifosfamide + Mesna

(9) For Vincristine/doxorubicin/cyclophosphamide (ANZ Ewings)(10) For Etoposide/ifosfamide/mesna (Ewings)

2. Ototoxicity

High frequency hearing loss can occur with cisplatin and audiograms can be used to monitor this.

3. Cisplatin Drug Interactions

Cisplatin/phenytoin:Effect

significant decrease in phenytoin level resulting in seizures

occurs with oral and IV

Mechanism ? decreased absorption


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? enhanced metabolism

? concomitant medicationsManagement

baseline phenytoin level

repeat level 2-3 days after cisplatin (and ? weekly)

may need to adjust dose during cisplatin to avoid failure

may need to readjust dose after cisplatin to avoid phenytoin toxicity

Cisplatin/aminoglycosidesClinical Studies

Early study in 4 patients on gentamicin and cephalothin severe progressive acute renal failure

Subsequent studies found renal impairment usually mild EXCEPT where pre-existing cisplatin-induced renaldysfunction was present when aminoglycosides were started.

ManagementFor patients with febrile neutropenia after cisplatin in whom aminoglycosides are indicated:-

check serum creatinine and weight

adjust dose accordingly

monitor levels (see page 38)

repeat monitoring if serum creatinine changes or in 3 to 5 days.

Cisplatin/lithiumEffectPossible decreased lithium level, but no reports of clinical effectMechanism? due to the cisplatin or the fluid loadManagementRecommend monitoring lithium level

ETOPOSIDE

Etoposide/phenytoin interactions:Reduced systemic exposure (? clinical significance) possible with etoposide

FLUOROURACIL

Fluorouracil (5FU) can cause chest pain, often accompanied by ECG changes and elevated cardiac enzymes indicative ofcardiac ischaemia. If this symptom occurs, discontinue the drug.Hand/foot syndrome with ambulatory infusion 5FU may respond to pyridoxine 100 to 150mg per day.

GRANULOCYTE COLONY STIMULATING FACTOR (G-CSF)

RAH INDICATIONS

Section 100 of the Pharmaceutical Benefits Scheme (P.B.S.) allows RAH to be reimbursed for certain High Cost drugs usedOUTSIDE hospital (ie d/c or OPD scripts). Granulocyte colony stimulating factor (GCSF) is one such drug. Use is restrictedto the following indications.

Oncology Tumour types for which G-CSF is reimbursable to allow full dose chemotherapy:

intermediate + high grade NHL

relapsed Hodgkins

first line Hodgkins (only for patients who have had a prior episode of severe febrile neutropenia or prolonged severeneutropenia {10,000 (if country patient self-administering, AMGEN filgrastim (in solution in pre-loaded syringe) is preferred)

or


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1 syringe filgrastim (Amgen - 300 mcg) s/c daily starting 24 hrs after CT is completed and continued for 10 days or untilWCC > 10,000. NB 480mcg syringe may be needed in pts > 96 kg.

Precaution omit on day bleomycin administered.

N.B. Blue Section 100 declaration form must be filled in by the doctor and sent with the first prescription for either brand.

The declaration states that the patient fits the criteria for Section 100 reimbursement. IT IS ONLY REQUIRED ONCE

MERCAPTOPURINE

Mercaptopurine & allopurinol interactionThis is the best known and most studied interaction, but the 2 drugs are often co-administered.

EffectSignificant increase in haematological toxicityMechanism

Allopurinol inhibits xanthine oxidase, the enzyme which metabolises mercaptopurine 5 fold increase in peakconcentration and AUC.ManagementReduce mercaptopurine dose to or 1/3 usual dose

METHOTREXATE

1. Third space collections

Patients with third space fluid collections, e.g. pleural effusions or ascites, should have them drained before methotrexate isadministered since severe myelosuppression may result by accumulation of the drug in such collections.

2. High dose methotrexate

Monitoring methotrexate levelsHigh dose methotrexate should be monitored, usually with 24 and 48 hour blood levels. Contact Haematology Lab25430.

Leucovorin RescueCalcium Leucovorin (calcium folinate, folinic acid) is used to rescue normal cells from methotrexate after HighDose infusions. The dose and timing varies with protocol, and must be strictly adhered to in order to avoid excessivetoxicity (severe mucositis, myelosuppression). A common rescue protocol is oral (or IV for the first dose) calciumfolinate 30mg every 6 hours for six doses (or until Serum MTX level is less than 0.1umol/l) commencing 24 hoursafter the START of methotrexate infusion.

3. Methotrexate Interactions

Well known potential for interactions with drugs that delay MTX clearance. The severity of toxicity is related to duration ofexposure and threshold concentrations (different for different organ systems).

Methotrexate/NSAIDS or Aspirin

EffectReports of the following toxicity with low dose MTX

cutaneous

g/i

pancytopaenia

severe mucositis liver dysfunction

deathMechanism

competition by weak organic acids for renal tubular secretion - delayed MTX clearance

inhibition of renal prostaglandin synthesis decreased renal perfusion

decreased protein binding (7-OH MTX is 91-93% bound)Management

caution when using concurrently - consider adding folinic acid, or increasing its dose or duration


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consider MTX level monitoring - consider withholding NSAID/aspirin during MTX

Methotrexate with trimethoprim +/- sulfamethoxazole

Effect

reported serious toxicity with low dose MTX

kinetic study in childhood ALL

66% increased systemic exposure and probable increased myelotoxicityMechanism

? additive folate antagonismManagementObserve for unexpected toxicity

Other reported suspected methotrexate interactionsIncreased toxicity (levels) with amiodorone, etretinate, omeprazole, penicillins, probenecid, remain to be confirmed.

OXALIPLATIN

Peripheral Sensory Neuropathy85-95% of patient experience neuropathy - two types acute and cumulative. NOT like cisplatin.

Acute peripheral sensory neuropathyThe majority of patients with neuropathy experience ACUTE neuropathy usually mild and painless, starts duringthe infusion (or within a few hours) and last from minutes to a few days. Characterised by dysaesthesia and/orparaesthesia of the extremeties with or without cramps. A SMALL percent (1-2%) experience acutepharyngolaryngeal dysaesthesia characterised by unpleasant (usually painless) sensation in throat, sometimesfeeling like shortness of breath, but without objective evidence of respiratory distress (hypoxia, laryngospasm,bronchospasm).ALL THESE SYMPTOMS CAN BE INDUCED OR EXACERBATED BY COLD.Precautions: keep warm. Wear thick gloves on cold days, and thin gloves for handling hot or cold items. Avoidbarefeet, swallowing food or drink that is either very hot or cold, avoid direct contact with cold water (warmshower/bath).

Treatment: acute laryngopharyngeal dysaesthesia increase infusion time from 2 to 6 hours; if have discomfortwith breathing have warm drinks, wear scarf or high necked sweater. Use of drugs is under investigation.

Jaw spasm, abnormal tongue sensation with possible subsequent dysarthria and feeling of chest pressure have beenobserved. Signs and symptoms rapidly reverse without treatment although antihistamines and bronchodilators havebeen used. Prolonging infusion time may reduce this on subsequent cycles.

Cumulative neuropathyPain and/or functional disorder may require adjustment of dose or cessation of oxaliplatin

Reference:P. Gent, K. Massey. An overview of chemotherapy-induced peripheral sensory neuropathy, focusing on oxaliplatin. International Journal

Of Palliative Nursing, 2001, Vo.7, No 7

Product information

PACLITAXEL

Hypersensitivity ReactionsPremedication as shown in Section TwoQuick premed is ranitidine 50mg IV, promethazine 25mg IV (or diphenhydramine 50mg oral) and dexamethasone 20mg IVapproximately 30 minutes prior to paclitaxel.

Reference:Bookman MA, Kloth DD, Kover PE, Smolinski S, Ozols RF. Short-course intravenous prophylaxis for paclitaxel-relatedhypersensitivity reactions. Ann Oncol. 1997 Jun;8(6):611-4.

Myalgias/ArthralgiasMay respond to prophylactic paracetamol or NSAID


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A number of other drugs including prednisolone may work in refractory cases. Consult Clinical Pharmacist.

STREPTOZOCIN

This drug should not be given in the presence of marked renal dysfunction Renal and hepatic function and glucose levelsshould be monitored during treatment (See ADEC guidelines).

VINCRISTINE

Vincristine InteractionsItraconazole increases neurotoxicity in children on vincristineNifedipine may decrease the clearance of vincristine

WARFARIN

See also page 21 Treatment of Venous Thromboembolism.Warfarin & Cytotoxic Drug interactionsAnticoagulants are often prescribed either for a pre-existing condition or for DVT or PE (thrombotic complications are oftenseen in cancer patients).

Warfarin & TamoxifenEffect

several individual reports and retrospective reviews significant increase in prothrombin times

significant bleeding problems in some casesMechanismUnknownManagementMonitor INR if stopping or starting tamoxifen

Warfarin & Ifosfamide/MesnaEffectRaised INR within 48 hours of starting ifosfamide/mesnaMechanism

? inhibition of warfarin metabolism

ManagementMonitor INR and adjust dose if needed

Warfarin & CyclophosphamideConflicting reports:

one report of raised prothrombin time on stopping oral cyclophoshamide 450 mg per day

4 other cases of raised prothrombin times or bleeding

monitor INR

Warfarin & Etoposide; Teniposide; 5FluorouracilRaised prothrombin or INR reported.

References:

Drug Interactions in the therapy of malignant disease. HJ Illiger et al, 3rd edition.Drug Interactions Facts, Editor David S Tatro

Henriksson R and Grankvist K. Interactions between anticancer drugs and other clinically used pharmaceuticals. Acta Oncologica 1989,28: 451-462

Balis F.M. Pharmacokinetic drug interactions of commonly used anticancer drugs. Clinical Pharmacokinetics 1986, 11: 223-235.Frenia ML and Long KS. Methotrexte and nonsteroidal anti-inflammatory drug interactions. The Annals of Pharmacotherapy, 1992, 26:234-5.Grossman SA, Sheidler VR and Gilbert MR. Decreased phenytoin levels in patients receiving chemotherapy. The American Journal ofMedicine, 1989, 87: 505-510.

Curtin JP et al. Chemotherapy-induced neutropenia and fever in patients receiving cisplatin-based chemotherapy for ovarian malignancy.Gynecologic Oncology, 1991, 40: 17-20


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Prevention & Management of Symptoms/Toxicities

W.H.O. (MILLER) TOXICITY GRADES

GRADES 0 1 2 3 4

Haemoglobin (g.dl)

11.0 9.5-10.9 8.0-9.4 6.5-7.9 < 6.5White cells (109/L) 4.0 3.0-3.9 2.0-2.9 1.0-1.9 < 1.0

Neutrophils (109/L) 2.0 1.5-1.9 1.0-1.4 0.5-0.9 110 at rest

unifocal PVC,atrial arrhythmia

multifocalPVC

ventriculartachycardia

Alopecia none minimal hairloss

moderate,patchy

complete -

Hand/foot syndrome none Mild moderate severe life-threatening

Cutaneous none Erythema drydesquamationvesiculation,pruritus

moistdesquamationulceration

exfoliativedermatitis, necrosisrequiring surgery

Haemorrhage none Petechiae mild blood loss gross blood loss debilitating bloodloss

Lethargy none mild moderate severe -

Fever none fever < 38oC fever 38-40pC fever > 40oCfever withhypotension

Pulmonary none mild symptoms exertionaldyspnoea

dyspnoeaat rest

complete bedrest required

Bladder none Mild moderate severe life-threatening

Allergic none Oedema bronchospasm,no parenteraltherapy needed

bronchospasm,parenteraltherapy required

anaphylaxis

Other none mild moderate severe life-threatening


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DOSE MODIFICATION FOR TOXICITY

Some general policies for dose reduction can be stated.Specific exceptions will be listed with specific treatment regimens using the WHO (Miller) toxicitycriteria:

HAEMATOLOGICAL: Grade 3 or 4 nadir neutrophil and platelet counts: reduce thesubsequent dosage by 25%. If neutrophils and platelets have notrecovered by Day 1 of next cycle delay therapy until neutrophilcount is 1500 and platelet count 100,000. May require 25%reduction for subsequent courses. Where Section 100 indication foruse of G-CSF is met, this should be considered for subsequentcycles (see G-CSF page 14)

NON-HAEMATOLOGICAL: For reversible grade 3 toxicity (except alopecia) may require dosereduction of 25%. Grade 4 non-haematological toxicities maydictate withdrawal of treatment or subsequent dose reduction of25%.


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ANTICOAGULATION - TREATMENT OF VENOUS THROMBOEMBOLISM

RAH Drug Committee Guidelines 2002

Low molecular weight heparin combined with oral warfarin is the treatment of choice for themanagement of venous thromboembolism.Administration of twice daily low molecular weight heparin should be commenced as soon as a decisionis made to anticoagulate the patient. Warfarin should be commenced on the day of admission andshould be co-administered until a therapeutic INR is achieved. The heparin dosages may then bereduced or ceased.The following algorithm provides an overview of management of venous thromboembolism with lowmolecular weight heparin and warfarin:

Strong suspicion of DVT or PE

Consider initiating treatment

before diagnosis confirmed

Perform appropriate

diagnostic investigations

Obtain baselineCBE, INR and APTT Diagnosis confirmed

Begin administration of enoxaparin 1mg/kg bodyweight (tonearest 2.5kg) subcutaneously twice daily (= total dailydose of 2mg/kg)

Syringes contain:60mg/0.6ml

or 80mg/0.8mlor 100mg/1.0ml

Select appropriate syringe sizeand inject calculated volume subcutaneously

Begin warfarin

Monitor INR daily. Adjust warfarin dose according to laboratory result

Discontinue enoxaparin when INR therapeutic on 2 consecutive days,and continue warfarin for at least 3 months

Monitor INR twice weekly for 2 3 weeks until stable therapeutic rangeachieved.

Monitor weekly or less frequently thereafter.


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Low Molecular Weight Heparin for Treatment of Venous Thrombosis and Pulmonary Embolus

Route and Method of AdministrationSubcutaneous: Severe bruising may result if an incorrect injection technique is used.The injection should be made into the anterior abdominal wall, using a different site for each injection. The whole length ofthe needle should be introduced vertically into the thickness of a skin fold pinched up between thumb and forefinger. This

skin fold should be held throughout the duration of the injection. Pressure should then be applied to the site with the palm ofthe hand for 5 minutes.

DosageNote: 1mg enoxaparin is equivalent to 100 units anti-Xa activityEnoxaparin 1mg/kg bodyweight, to nearest 2.5kg bodyweight subcutaneously twice daily.Laboratory ControlBefore therapy is commenced, send 4ml of blood in a blue top container for determination of International Normalised Ratio(INR, previously called prothrombin ratio (PR)), and activated partial thromboplastin time (APTT) and to exclude a pre-existing coagulation problem. Once therapy has been commenced, laboratory monitoring of low molecular weight heparinanticoagulant activity is unnecessary, however platelet counts should be monitored weekly to detect heparin inducedthrombocytopaenia.

Duration of TherapyHeparin is usually ceased when the INR is therapeutic for 2 consecutive days, and oral anticoagulants are then continued forat least 3 months. Heparin should be continued until warfarin is having a therapeutic effect (see Section 2.2 for therapy withoral anticoagulants).

Overdosage or Bleeding ComplicationsIn emergency situations, the anti-coagulant activity of low molecular weight heparin may be largely neutralised byintravenous protamine sulfate, (1mg protamine sulfate neutralises 1mg of enoxaparin). However, some anti-Xa activity willremain. The Haematologist on call or the Pharmacy Drug Information Centre (Ext. 25546) should be consulted for furtheradvice concerning dosage in these situations.

Oral AnticoagulantsNote: It is recommended that prior to discharge of a patient with warfarin therapy for long term anticoagulation, the

patient is counselled and provided with written patient information.Contact clinical pharmacist Page 1507Alternatively the advice of the Drug Information Centre may be sought on Ext 25546.

Laboratory ControlBaseline coagulation studies should be performed before starting therapy; send 4ml of blood in a blue top container forInternational Normalised Ratio (INR), and activated partial thromboplastin time (APTT) determination and to exclude acoagulation disorder. R.A.H. ranges for normal INR and normal APTT are 0.8-1.2 and 20-39 seconds respectively.Subsequent monitoring is by the International Normalised Ratio (INR).

DosageThe recommended initial dosage for warfarin is 6 - 10mg/day (depending on age, according to loading protocol below),with daily adjustments made thereafter depending on laboratory results. The average maintenance dose varies from 2 to10mg although some patients require doses outside this range.Due to the long half-life of warfarin, the maximum effect of a dose is seen 48-72 hours after administration. Two to-3weeks are generally required for full stabilisation on warfarin therapy.

Warfarin dose should be given at 6pm each day during the loading phase

Blood samples for INR should be taken between 9am11am the next morning

INR must be performed daily for the first 5 days

Some patients may require further marginal dosing adjustment at the completion of the protocol

The goal of warfarin loading regimens is to rapidly attain a stable therapeutic INR without over-anticoagulation. If thebaseline INR (before commencement of warfarin) is 1.4 or more then careful consideration must be given to initiatingwarfarin for any condition.

The recommended therapeutic range for oral anticoagulant therapy is 2.0 - 3.0. For patients with prosthetic heart valves the

recommended ranges are 2.0 - 3.0 (low risk valves) and 2.5 - 3.5 (high risk valves).


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The following Age Adjusted Warfarin Loading Protocol* is a guide to warfarin dosing during the induction period.

Dose according to age (mg)

Day INR 50 years 5165 years 6680 years >80 years

1 4 0 0 0 0

4 (16hrs after 3rd dose) 1.5 1015 914 7.511 69

1.6 8 7 6 5

1.71.8 7 6 5 4

1.9 6 5 4.5 3.5

2.02.6 5 4.5 4 3

2.73.0 4 3.5 3 2.5

3.13.5 3.5 3 2.5 2

3.64.0 3 2.5 2 1.5

4.14.5 omit next dose, then

12 0.51.5 0.51.5 0.51

>4.5 Nil. Hold dose.

* Roberts GW, Gallus AS, Druskeit T et al. Comparison of an age adjusted warfarin loading protocol with empirical dosing

and Fennertys protocol. Aust NZ J Med. 1999; 29: 731-6.

Duration of Warfarin TherapyFor treatment of thromboembolism, warfarin therapy is usually continued for 3 months

Management of In-patient Maintenance Warfarin TherapyFollowing admission of any patient on maintenance warfarin therapy to the R.A.H., the maintenance warfarin dose should bewritten on the Medication Chart for Regularly And Intermittently (PRN) Administered Drugs (UR-71B). Testing for INR

should be performed every two or three days. The medical officer responsible for the care of the patient is responsible forchecking the INR result on the day of the test. However in the event that:

(a) A new drug is ordered, or a drug is ceased, which is suspected of interacting with warfarin, or(b) The INR falls below, or rises above, the recommended therapeutic level,

the order for regular doses of warfarin should be discontinued, and a new variable dose warfarin order commenced, withdaily testing of INR, followed by subsequent selection of an appropriate dose for that day guided by the results of the INRtest. The new variable dose warfarin order may be written on either the UR-71B, or Medication Chart For Variable DoseDrugs (UR-72), according to usual ward practice. Patients should not be changed from their usual brand of warfarin. TheRAH Pharmacy Department stocks both brands of warfarin.

Tablet strengths and colours are:COUMADIN

1mg (light tan), 2mg (lavender), 5mg (green) RAH brand of warfarin for initiation of warfarin therapyMAREVAN

1mg (brown), 3mg (blue), 5mg (pink) Specify this brand if patient usually takes it.


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Drug InteractionsRegular monitoring of warfarin is mandatory. There is significant potential for drug interactions with warfarin therapy.Caution should be exercised when adding or deleting any newly approved drug until its safety in combination with warfarinis known. Changes in warfarin effect can occur with either the introduction or cessation of drug therapy. Bleeding is the mostimportant adverse effect. The concomitant use of antiplatelet drugs (e.g aspirin, NSAIDs, clopidogrel, ticlopidine,dipyridamole) can also increase the risk of bleeding. Some complementary medicines (eg ginkgo, dong quai) may also havean antiplatelet effect.The elderly, the critically/acutely ill, those with impaired renal function, those with impaired hepatic function and thosetaking multiple drug therapies are particularly at risk. Those patients with fluctuating dietary intake may require morefrequent INR monitoring, e.g. patients with anorexia, nausea, vomiting and diarrohea.

This is not an exhaustive list of potential drug interactions

Increased anticoagulant effect Decreased anticoagulant effect

Amiodarone, Anabolic steroids, Bicalutamide, Chloramphenicol,Cimetidine, Ciprofloxacin, Clarithromycin, Cotrimoxazole, Danazol,Disulfiram,Dong quai, Doxycycline, Erythromycin, Fluconazole,Flutamide, Gemfibrozil,Ginkgo biloba, Itraconazole, Ketoconazole, Metronidazole,Miconazole (including oral gel), Nilutamide, Norfloxacin, Protease

inhibitors (indinavir, saquinavir, ritonavir, nelfinavir), Quinidine(also decreased), Simvastatin, SSRIs, Sulphinpyrazone, Tamoxifen,Tetracycline, Thyroxine, Paracetamol.

*Small occasional doses of paracetamol do not normally affect INR.Larger amounts of paracetamol (2 to 4 grams daily) taken for severaldays may increase the INR. More frequent monitoring is indicatedespecially if paracetamol administration coincides with other riskfactors, eg febrile illness.

Barbiturates,

Carbamazepine

Cholestyramine

Griseofulvin

Non-nucleoside reverse transcriptase inhibitors (some -nevirapine, efavirenz)

Nutritional supplements rich in Vitamin K

Phenytoin (or more rarely increased)

Rifampicin

St. Johns Wort (Hypericum perforatum)

Sucralfate

Overdosage

In any case of overdosage specialist haematologist advice may be sought if necessaryThe appropriate antidotes to warfarin overdosage are Vitamin K1 (phytomenadione), alone or with fresh frozen plasma (2-4units) +/- Prothrombinex (Factor II, IX and X concentration) -1200-2400 units IV.Note: (a) The use of Prothrombinex has been associated with an increased incidence of thromboembolism.

(b) The dangers of viral transmission associated with blood products must be considered.(Patient consent must beobtained.

The effect of fresh frozen plasma is immediate whereas it takes 8-12 hours for the effects of Vitamin K1 to become apparent.Large doses of Vitamin K1 (eg 10-20mg) may produce some resistance to re-warfarinisation, but there is less resistance tosmaller doses of 1-5mg, which are still effective in correcting an abnormally high INR within 24 hours in most cases.

Vitamin K1 should be given by the oral route, except where there is malabsorption or obstructive jaundice. If using parenteral

vitamin K1 (Konakion MM), the IV route is recommended. The required dose should be given at a rate equivalent toadministering 10mg (1ml) over a minimum of 30 seconds. A maximum total dose of 40mg in 24 hours. IV phytomenadionemay in rare cases cause severe anaphylactoid reactions. It should not be administered intramuscularly as this route ofadministration exhibits depot characteristics which may cause difficulties in the reinstitution of anticoagulant therapy.

The following table provides a guide to reversal of the anticoagulant effect of warfarin

Clinical Picture INR Warfarin Vitamin K1 Dose FFP +/- Prothrombinex

Significant bleeding Therapeutic or above Hold 0mg (IV if bleeding severe) 2 - 4 units

No bleeding >10 Hold 1-3mg 2 units

No bleeding 7-10 Hold 1-3mg .

No bleeding 4.5-7 Hold for 1-2 days . .

Elective surgery Therapeutic Hold for 3-4 daysbefore surgery

. .

Semi elective surgery(24-48 hours available)

Therapeutic Hold 5mg .

Emergency surgery (< 24hours available)

Therapeutic Hold 5mg 2 - 4 units


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CONSTIPATION

Prevention/Treatment of Opioid Induced Constipation

Precautions:1. Neutropenic patients should not have rectal suppositories2. Prior to giving laxatives or enemas ensure that tumour related bowel obstruction is not the

underlying cause.

1. Commence regular laxative protocol on initiation of opioid analgesia.(a) Coloxyl with Senna 1-2 tablets twice daily strictly (acts in 6 to 12 hours).(b) Encourage mobilisation, fluids and increased fibre intake. (Note: Increased fibre

is contraindicated in bowel obstruction and in debilitated, dehydrated patients).

2. Chart and describe bowel actions daily.

3. Increase dose of Coloxyl with Senna if necessary up to 2 tablets three to four times daily.

4. Rectal examination should be performed if patient has:-(a) rectal discomfort(b) no bowel action for 3 days

5. If rectum full the following should be tried sequentially.(a) glycerin suppository or disposable enema (eg microlax).(b) high enema by flexible catheter (eg. glycerin and oil or tap water).(c) magnesia pellegrino (15 ml in water stat) (acts in 2 to 4 hours).(d) manual evacuation.

6. For persistent constipation add alternate day glycerin suppository or disposable enema to dailyColoxyl with Senna.

7. Patients presenting with pre-existing opioid-induced constipation require treatment as in (4) and (5)and commencement of regular laxative protocol as in (1).

8. Alternative laxatives eg. sorbitol (osmotic laxative) 20 ml TDS should be reserved as third line.Onset of effect may take several days. Requires good hydration to work, and does not stimulatebowel motility. Use with caution in diabetics as it may elevate blood glucose levels (usually afterextended use). Tolerance is also reported after prolonged use. Lactulose another osmotic laxative issignificantly more expensive than sorbitol and at RAH lactulose is ONLY available for treatment ofhepatic encephalopathy, NOT constipation. Many patients find sorbitol/lactulose unpalatable.

9. Remember diarrhoea may be due to faecal impaction with overflow.


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DIARRHOEADiarrhoea in the cancer patient can be:

an extension of chemotherapy-induced stomatitis (oral mucositis)

caused by drugs (e.g. capecitabine, fluorouracil, irinotecan)

a symptom of constipation (overflow)caused by radiotherapy especially to pelvic area (e.g. for colorectal; prostate or cervix cancer)

PREVENTION/TREATMENT

1. IRINOTECANIrinotecan can induce two distinct types of diarrhoea:

EARLY DIARRHOEA

early diarrhoea occurs during or soon after administration, is cholinergic in nature and may be accompanied by rhinitis,increased salivation, miosis, lacrimation, diaphoresis, flushing and hyperperistalsis that can cause abdominal cramping

atropine 250 micrograms to 1 mg IV or SC can be used to prevent or treat early diarrhoea

LATE DIARRHOEA

late diarrhoea occurs >24 hours after the dose, can be prolonged, and may lead to dehydration, electrolyte imbalance andis potentially life-threatening. PROMPT TREATMENT IS ESSENTIAL.

patients must have loperamide available and start taking it at the first episode of poorly formed or loose stools, or theearliest onset of more frequent than usual bowel movements for that patient.

high dose loperamide is used 4mg (2 capsules) STAT then 2mg every 2 hours (or 4mg every 4 hours during the night)until diarrhoea free for 12 hours. Patients should notify the doctor and need careful monitoring and fluid/electrolytereplacement if dehydrated. Make sure the patient understands that the dose will be higher than recommended on thepack, and that this is intentional.

2. CAPECITABINE, FLUOROURACIL

Determine the NCIC grade of diarrhoea, and follow the guidelines below.

Grade 2 Grade 3 Grade 4

Increase of 4 - 6 stools/day ornocturnal stools

Increase of 7-10 stools/day orincontinence and malabsorption

Increase in 10 stools/day orgrossly bloody diarrhoea or need for

parenteral support

*NCIC National Cancer Institute of Canada

If grade 2, 3 or 4 diarrhoea occurs, treatment should be immediately interrupted until the diarrhoea resolves or reduces toGrade 1.

Start standard antidiarrhoeal treatment with loperamide 4mg to start and 2mg after each loose stool until diarrhoea iscontrolled (maximum 16mg per 24 hours).

Subsequent dosing:-

NCIC Grade Dose

2 100%

3 1st occurrence - 25% reduction

2nd occurrence - 50% reduction

3rd occurrence - discontinue permanently

4 Discontinue permanently or reduce by 50%


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EMESIS

1. Chemotherapy-Induced Emesis

INTRODUCTION

Nausea and vomiting associated with cancer chemotherapy can be severely distressing and debilitating to patientsand may even lead to refusal of further chemotherapy unless controlled.

It is possible to categorise cyotoxics into five groups according to their emetogenic potential, and recommendappropriate antiemetics for each group.

It should be noted that combinations of cyototoxics are usually more emetogenic than single agents. Likewisecombined antiemetic regimens are significantly more effective than single agents particularly with severelyemetogenic cytotoxic drugs.

In addition to the variation in emetogenicity of individual cytotoxics, other factors may influence the severity ofemesis. These include the dose and schedule of the cytotoxic, the patients age, sex, alcohol intake history, prioremetic history and concurrent medical problems

All patients regardless of cytotoxic protocol should have PRN antiemetics available

TYPES OF EMESIS

Chemotherapy-induced nausea and vomiting are classified as acute, delayed, anticipatory, breakthrough or refractory.

Acute nausea and vomiting usually occurs within the first few hours after chemotherapy (see Table I) and lasts upto24 hours

Delayed vomiting starts about 24 hours after chemotherapy, and may last a week or longer. It is most common withcisplatin

Anticipatory nausea and vomiting is learned from previous experience with poorly controlled vomiting.

Breakthrough vomiting occurs despite optimum preventitive therapy, and requires additional therapy.

Refractory vomiting occurs after one or several cycles of chemotherapy when the patient no longer responds totreatment.

DRUG CLASSES AND RECOMMENDED ACUTE ANTIEMETIC PROTOCOL

Class V (very high emetic incidence - > 90% patients vomit)

DRUG & DOSE if relevant ONSET

(hours)

LASTS

(hours)

ANTIEMETIC PROPHYLAXIS PROTOCOL

Acute Emesis

carmustine 250mg/m2 2- 4 4-24

cisplatin# Acute 1- 6Delayed 16-24

>247days+

cyclophosphamide >1.5g/m2#

6-18 18-36

Dacarbazine 1- 3 6-24

lomustine > 60mg/m2 2- 6 6-12

Streptozocin 1- 4 12-24

Tropisetron 5mg oral (or IV if vomiting) orondansetron 8mg oral wafer (Zydis) if cannotswallow capsule (more expensive)+Dexamethasone 20 mg IV over 30 minutes prechemotherapy+

for severe acute or anticipatory emesis

Lorazepam 1 3mg oral or sublingual pre

chemotherapy

#requires delayed emesis antimemetic protocol

*Information unavailable.


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Class IV (moderate to high emetic incidence - 60-90% patients vomit)


(hours)

LASTS

(hours)


Acute Emesis

Carboplatin# 2-10 48

carmustine < 250mg/m2 2- 4 4-24

cyclophosphamide 750-1500mg/m2

4-12 4-10

cytarabine 1g/m2 6-12 3-5

dactinomycin > 1.5mg/m2 2- 6 12-24

Daunorubicin >50mg/m2 2- 6 60mg/m2 2- 6 6-24+

ifosfamide > 3.5g/m2 3- 6 6-24+

Irinotecan 2-6 6-12

lomustine < 60mg/m2 2-6 6-12

melphalan (high dose IV) 6-12 *

methotrexate _ 1g/m2 4-12 3-12

Tropisetron 5mg oral (or IV if vomiting) orOndansetron 8mg Zydis if cannot swallowcapsule (more expensive)+Dexamethasone 20 mg IV over 30 minutes prechemotherapy

#may require delayed emesis antiemetic protocol

*Information unavailable.

Class III (moderate emetic incidence - 30 - 60% patients vomit)


(hours)

LASTS

(hours)


Acute Emesisaltretamine 3-6 *

Cyclophosphamide 38.5oC or if a neutropaenic patient beginsto feel unwell, or develops rigors or hypothermia. Cultures of blood, urine plus sputum, skin lesions, throat orvagina if indicated should be taken. Perineal area can be a common source of infection. Chest x-ray should betaken.

EMPIRICAL ANTIBIOTIC THERAPY FOR FEBRILE NEUTROPAENIA

NO PENICILLINALLERGY

PENICILLIN ALLERGY SHOCK OR SEPSIS

Timentin3.1g 6 hourlyPLUS

Gentamicin(see Gentamicin Dosing

and MonitoringGuidelines)

cefepime 2 g 12 hourlyfor 72 hours, then 1 g 12hourly if clinically stable

and culture negative

PLUSGentamicin

(see Gentamicin Dosingand Monitoring

Guidelines)

ADDvancomycin to empiricregimen

(see Vancomycin Dosingand Monitoring

Guidelines)

In the presence of renalimpairment

CHANGE tomeropenem 500 mg

8-12 hourlydepending on creatinine

clearance

(Do not use cefepime ifprevious severe reaction toa beta-lactam. Obtain

Infectious Diseases adviceregarding an alternative

agent antibiotic.)

Review therapy ifpositive culture or noimprovement after 48hours (see InfectiousDiseases protocols)

Meropenemused whenrenal dysfunction precludes gentamicin use.Dose500 mg 8 hourlyIn renal impairment:

Creatinine clearance Meropenem Dose26-50 ml/min 500mg 12/24

10-25 ml/min 250mg 12/24


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3. GENTAMICIN DOSING & MONITORING

gentamicin is potentially nephrotoxic, ototoxic and vestibulotoxic

toxicity is largely predictable and, in the case of nephrotoxicity, reversible

toxicities are cumulative and even when appropriate doses are used, toxicity will inevitably occur after 10 to15 days of continuous treatment

gentamicin is cleared almost entirely unchanged by renal filtration failure to modify dose in renal dysfunction results in more rapid accumulation and a more rapid onset of

clinical toxicity single daily dose is as effective and less nephrotoxic than in divided doses

a) CALCULATE CREATININE CLEARANCE

CL CR = (140 age) x wt (lean BW if obese) X 0.85 if female

815 x se creatinineLean Body Weight Male: 50kg + 0.9kg for each cm > 150cm height;

Female: 45kg + 0.9kg for each cm > 150cm height

b) CALCULATE FIRST DOSE - THERE ARE 3 OPTIONS

CrCl > 60ml/min7 mg / kg (lean BW if obese)

over 15 mins

CrCl 20 to 60 ml/min5 mg / kg (lean BW if obese)

over 15 mins

CrCl < 20 ml/minDo not use gentamicin

(consult ID)ROUND all doses to nearest 40 mg max. dose 640 mg.

Write dose as variable and when dose determined write on administration chart

c) MONITOR LEVELS FOR FIRST DOSE THEN ONCE MORE(or more often if renal function unstable, or the patient will be on gentamicin for > 5days)

FIRST LEVEL PEAKTake blood at 30 mins to 2 hours after infusion

finished

SECOND LEVELTake blood at 6 to 10 hours after dose

(This is NOT a trough level)IF THE SAMPLING TIME IS NOT RECORDED IT AND CANNOT BE USED

d) DOSE CALCULATION VIA COMPUTER PROGRAMME

Weekdays 9am to 5pmPage Clinical Pharmacist 1507 or Antibiotics

Pharmacist 1609

Weekends 9am to 4.30pmRing Level 2 dispensary Ext.25418

WHAT INFORMATION SHOULD YOU HAVE READY?FIRST LEVEL

Patient nameUR number

WeightHeight

CreatinineAge

GenderDate givenDose givenTime started

Time levels taken and results

SUBSEQUENT LEVELSRing before the next dose is due (if you have several do them all at once)

Avoid doing levels on Fridays/Saturdays unless essential. If required on weekends, adispensary pharmacist will put the results through if you provide all the information

(Ext 25418).

If you order levels Friday or Saturday dont forget to tell the w/end MO for the nextday to check the results & have them put through the program for dose calculation

WHAT ARE WE AIMING FOR?

Cmax of15 ( 8-10 x MIC) or >20 for pseudomonas; AUC 70 to 100; Cmin


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4. HELICOBACTER PYLORI

First-Line Treatment:(commercially available as Losec HP7)

Omeprazole 20 mg bd

Amoxycillin 1 g bdClarithromycin 500 mg bd All for 7 days

For patients with penicillin allergy:

Omeprazole 20 mg bdClarithromycin 250 mg bdMetronidazole 400 mg bd All for 7 days

References:Misiewicz JJ, Harris AW, Bardhan KD et al. One week triple therapy for Helicobacter pylori: a

multicentre comparative study. Gut 1997;41:735-9.Lind T, Veldhuyzen Van Zanten S, Unge P et al. Eradication of Helicobacter pylori using one-weektriple therapies combing omeprazole with two antimicrobials: The MACH 1 Study. Helicobacter1996;1:138-44.

5. T.B. PROPHYLAXIS

In patients with a history of TBIsoniazid 300 mg oral dailyPyridoxine 25mg oral daily (to prevent neuropathy)

Consider the possibility of isoniazid resistance (e.g. younger patient, migrant) and in those cases seekthe advice of the Infectious Diseases Unit.

6. VANCOMYCIN DOSING AND MONITORING GUIDELINES

Dosage and Administration

usual dose: 1g IV 12 hourly

ideal daily dose (mg/day) = 15-20 x creatinine clearance (CrCl) mL/min

adjust total daily dose to the closest increment of 500mg

dosage based on renal function

CrCl > 75 mL/min: 1g every 12 hours

CrCl 50-75 mL/min: 500-750mg every 12 hours

CrCl 10-50 mL/min: 500mg-1g every 24-48 hours

CrCl < 10 mL/min: 500mg-1g every 4-10 days

infuse dose over 1-2 hours (10mg/minute)

higher doses may be necessary for endocarditis, meningitis, obesity and burns (consult InfectiousDiseases or Clinical Microbiology)

Therapeutic Drug Monitoring

Vancomycin levels should be monitored if:

concurrent treatment with nephrotoxic drugs (e.g. gentamicin, cyclosporin)


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unstable renal function

endocarditis or meningitis

duration of therapy longer than 7 days

Vancomycin levels are not indicated if: short term therapy (e.g. < 7 days) in patients with normal renal function

When levels are required:

take the first level before the 5th dose (usually on day 3)

take a trough level within 1 hour before the next dose

repeat level once weekly thereafter (if renal function is stable) normal trough level = 5-15 mg/L

In renal impairment:

take daily levels initially to determine dosing interval

give next dose when level falls within the normal range (5-15 mg/L)

once dosing interval is established, daily monitoring is no longer required (if renal function isstable)

for advice contact Pharmacy, Infectious Diseases or Clinical Microbiology

Additional information

vancomycin is a glycopeptide antibiotic, not an aminoglycoside (e.g. gentamicin)

vancomycin exhibits time-dependent bactericidal action

monitor serum creatinine during treatment

nephrotoxicity is rare without concomitant aminoglycoside use

routine monitoring of vancomycin levels for all infections is unnecessary

7. VIRAL INFECTIONS in Immunosuppressed Patients

See RAH formulary for details:

Primary Herpes Simplex Or Episodic Recurrent Herpes Simplex

Famciclovir 500mg every 8 hours for 7 daysor in severe casesAcyclovir 5 mg/kg IV every 8 hours for 7 days

Chicken Pox Primary Or Initial InfectionAcyclovir 10mg/kg IV every 8 hours for 10 daysor in less severe cases as an alternative to IV treatmentFamciclovir 500mg oral every 8 hours for 10 days

Herpes Zoster - to prevent disseminationFamciclovir 500mg oral every 8 hours for 10 daysorAcyclovir 10mg/kg IV every 8 hours for 10 days

Renal impairment may necessitate dosage reduction (see RAH formulary).


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MOUTH CARE GUIDELINES

1. CHEMO-RADIOTHERAPY MUCOSITIS PROTOCOL

All patients receiving potentially stomatotoxic drugs or head and neck radiotherapy, must be

commenced on a prophylactic mouth care protocol. Should mucositis occur, the mouth care protocol forthe appropriate signs/symptoms should be added.

Drugs likely to cause stomatoxicity include:

fluorouracil (infusion)

methotrexate

epirubicin

lomustine

etoposide

doxorubicin

bleomycin

ORDER OF ADMINISTRATION1. PAIN:- analgesic mouthwash first (before meals and if severe pain before other mouth care).2. CLEANSING:- after meals and at night (wait 10 minutes before using other mouthcare)

3. ANTIFUNGAL TREATMENT

4. MOISTURISER to lips (e.g. lanolin)

2. DRY MOUTHFor dry mouth secondary to radiotherapy

Pilocarpine Solution 1mg/ml, 5mg tds to start. Add 5mg at bedtime after 7 daysResults may take 90 days or longer

Adverse Effects - flushing and sweating which may be dose limiting.

Contraindication - uncontrolled asthma or when miosis is undesirable.

PROPHYLAXIS1.Good toothbrushing technique2. Warm water/saline rinse after meals and at night

(Amosansachet in a glass of warm water may be used as an alternative)

IF MUCOSITIS OCCURS

Continue cleansing as for prophylaxis, and add the following as required

FOR PAIN, ULCERS

Benzydamine mouthwash 10ml swishedfor 3 minutes BEFORE meals (may be

diluted with warm water if stingingoccurs)AND/OR

systemic analgesia 60 minutes beforemeals if necessary.

FOR CANDIDA

Nystatin drops1ml swished in mouth

QID after meals(miconazole oral gel

spoon QID is analternative)


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4. DRUG THERAPY

4.1 Mild to Moderate Pain (Step 1 Analgesic Ladder)

DRUG DOSEParacetamol 500mg 2 tablets 4 hourly

IF PAIN NOT CONTROLLED USEParacetamol 500mg/Codeine Phosphate 8mg 2 tablets 4 hourly

(Panadeine, Codalginor Dymadon Co)

ORParacetamol 500mg/Codeine Phosphate 30mg 1 - 2 tablets 4 hourly(Panadeine Forte)

ORParacetamol 1000mg/Codeine Phosphate 60mg/10ml 5 - 10ml 4 hourly(Panadeine Forte Syrup) Prepared by RAH Pharmacy

Although these drugs are mentioned here, for persistent ongoing pain codeine is not the opioid of choice, and fixedcombinations of drugs are not recommended.

4.2 Moderate to Severe Pain (Steps 2 and 3 of Analgesic Ladder)

Simple analgesicParacetamol 500mg 2 tablets 4 hourly

OR

Anti-inflammatory (if appropriate) Particularly useful in bone pain, by inhibition of prostaglandin synthetase,

Salicylates use aspirin with caution in potentially thrombocytopaenic patients.

NSAIDS according to usual prescribing guidelines. COX II inhibitors - if compliant with RAH Drug Committee restrictions.

PLUS

Opioid

Morphine is the usual first choice opioid.

There is no maximum dose for pain relief. The correct dose is that which relieves pain without producing intolerable sideeffects.

Morphine dose should be titrated carefully until pain is relieved using a short acting (immediate release) formulation. Slow release morphine formulations should not be commenced until dose requirements are known.

4.2.1 Oral Morphine

DOSAGE FORM DOSE SCHEDULE

Morphine oral solutionAvailable in strengths of 1mg/ml, 2mg/ml, strictly 4 hourly5mg/ml, 10mg/ml

Tip: Patients should be taught to think of their dose in mg of morphine, not mls of solution

Morphine sulfate tablets strictly 12 hourly

controlled releaseMS Contin (sometimes needed 8 hourly)5mg, 10mg, 15mg, 30mg, 60mg, 100mg

Tip: tablets must not be crushed or chewed.

Morphine sulfate capsules(two brands, different strengths available)

sustained releaseKapanol strictly 12 hourly or10mg, 20mg, 50mg, 1000mg strictly once every 24 hours

Tip: capsules may be opened and the pellets sprinkled on soft foodpellets must not be crushed or chewed.

sustained releaseMS MONO strictly 12 hourly or10mg, 30mg, 60mg, 90mg strictly once every 24 hours

Morphine sulfate suspension

sustained release sachetsMS Contin strictly 12 hourly30mg, 60mg, 100mg (sometimes needed 8 hourly)Tip: The granules in 1 sachet should be reconstituted with 10ml water, mixed thoroughly and taken immediately. Suitable for use

through wider bore feeding tubes.


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Dose

Starting dose of morphine depends on: previous opioid use eg Panadeine Forte, oxycodone

age

intensity of pain.

eg. opioid naive patient with mild to moderate pain, usual starting range morphine is 2.5 to 10mg orally 4 hourly, with

breakthrough dose of 2.5 to 5mg as needed. If pain is not controlled after 2 to 3 oral doses, increase dose for a further 2 to 3doses and titrate until pain is controlled for 4 hour period.

Starting Slow Release Formulations

establish the total dose of oral morphine needed in a 24 hour period to control pain and divide into two for the 12 hourlydose

give the last dose of mixture with the first dose of slow release morphine

prescribe oral morphine solution for breakthrough pain usually 1/6 1/10 total daily dose every two hours if needed.

Tip: Remember as total daily dose increases breakthrough dose will need to be increased.eg

For MS Contin 30mg bd, breakthrough dose 10-15mg morphine solution 2 hourly prnFor MS Contin 200mg bd, breakthrough dose 50-70mg morphine solution 2 hourly prn

4.2.2 Subcutaneous morphine

The subcutaneous route is used:

for rapid pain relief in severe pain*

if oral route unavailable eg vomiting

if side effects are troublesome eg constipation, nausea, confusion S/C route enables dose reduction.

* In severe acute pain the intravenous route and Acute Pain Protocol can be used to allow more rapid titration of opioid. Use ofthis protocol is restricted to approved units.

Method

A butterfly needle is inserted eg into infraclavicular region and morphine administered either: intermittently bolus doses 4 hourly with breakthrough doses as required, OR by continuous infusion eg Graseby syringe driver pump

the improved bioavailability compared to the oral route means the equ ivalent S/C dose is 1/3 oral dose

to commence S/C infusion, calculate previous total daily opioid use as morphine oral equivalents and d ivide by 3

remember to order S/C breakthrough dose, usually 1/6 - 1/10 of the total daily dosether drugs - compatibilityOther drugs compatible with morphine in syringe: (Usual maximum of three drugs combined)

anti-emetics - metoclopramide 40mg/24 hours (or less) to start- haloperidol 2.5 mg/24 hours to start (larger doses may precipitate

anxiolytic -midazolam 5-7.5/mg25hours to start (at 10-15mg/24 hours sedation seen)anticholinergic - hyoscine hydrobromideantispasmodic - hyoscine butylbromide60 to 80 mg/24 hours to start

Intraspinal morphine4.2.3 Other Routes

Epidural or intrathecal routes allow further reduction in morphine dose and possible combination with local anaesthetic agents. Contact

Chronic Pain Service for advice.

Morphine intolerance

If side effects from morphine prevent dose escalation to achieve pain control, consider:

dose reduction by using an alternative route of delivery eg. oral S/C, S/C intrathecal.

adding suitable co-analgesics to reduce morphine requirements changing to alternative opioid


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4.2.4 Alternative Opioids

4.2.4.1 Fentanyl

indicated for use in patients with morphine intolerance, renal failure, or intermittent or sub-acute bowel obstruction

single doses are very short acting but fentanyl can be delivered by continuous S/C infusion or continuous transdermal patch

transdermal fentanyl patches (Durogesic

) are available as 25 mcg/hr, 50 mcg/hr, 75 mcg/hr and 100 mcg/hr (see RAH DrugCommittee Guideline for conversion dose). The duration of the patch is 72 hours the lowest strength patch, 25mcg/hr, is equivalent to a daily dose of 60-90mg oral morphine

when commencing transdermal fentanyl, remember slow onset (24 to 72 hours to peak analgesia, so additional analgesia may berequired at first) and offset 12-24 hours

transdermal fentanyl should not be commenced in the opioid nave patient.

4.2.4.2 Oxycodone

Oxycodone immediate release oral tablets (Endone 5mg) or capsules (Oxynorm 5mg, 10mg, 20mg) every 4 to 6 hours

Oxycodone 30 mg rectal suppositories (Proladone) usually for night time use

Oxycodone 10mg, 20mg, 40mg, or 80mg slow release tablets (Oxycontin) every 12 hours.

4.2.4.3 Methadone

Methadone has variable equianalgesic dose compared with other opioids which is due to its complex pharmacokinetic andpharmacodynamic properties. There is potential for severe toxicity due to accumulation, and it is suggested to seek advice from ChronicPain or Palliative Care units before use. Factors include:

prior opioid use

long and highly variable half life - need to titrate cautiously, preferably as an in-patient

wide interpatient variability in bioavailability and duration of analgesia

prolonged time to steady state after dose change (4 to 5 days) age (use particular caution in the elderly)

Methadone blocks NMDA receptors.

4.2.4.4 Hydromorphone

recently re-marketed in Australia higher lipid solubility than morphine

better oral bioavailability and 5 - 7 times more potent than morphine

may replace pethidine

refer to RAH Drug Committee Guidelines for use

5. EQUIANALGESIC DOSES TABLE

Equianalgesic DosesDrug

IM (S/C) ORAL

Duration OfEffect (hours)

Other Comments

Morphine 10 30 3 - 4 Extensive first pass effect

Methadone variations seen in

equianalgesic dose

variations seen in

equianalgesic dose

4 - 48 + Initial doses need careful

titration. Accumulationoccurs

Pethidine 100 300 400 2 - 3 Not recommended for use inchronic cancer pain

Fentanyl 0.15 - 0.5 - 1 Less constipation thanmorphine

Oxycodone 30 4 - 6 Suppository has longerduration (8-10 hours)

Hydromorphone 2 4 6 3 - 4

Codeine 130 200 4 - 6 Very constipating


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6. CO-ANALGESICS (ALSO KNOWN AS ANALGESIC ADJUVANTS)Use of co-analgesics will generally allow pain control at lower opioid doses. They should be considered from the start ofpain treatment.6.1 Tricyclic antidepressants

Useful for continuous or lancinating neuropathic pain.Response is usually seen in the first few days, at doses lower than antidepressant action. A trial of 2 weeks should be

considered before discontinuing.

amitriptyline or 25 75mg oral at nightdoxepin ordothiepin

6.2 AnticonvulsantsParticularly useful in lancinating or episodic pain, but can be tried in any neuropathic pain

clonazepam 0.25 0.5mg TDS oral or S/Csodium valproate 200mg BD to TDS oral with mealscarbamazepine 100 - 200mg BD oral

6.3 Local anaesthetics

For burning dysaesthesia, or lancinating painlignocaine S/C 500 - 1000mg/24 hoursmexiletine 50 - 200mg TDS oral

6.4 CorticosteroidsUsed for pain related to nerve compression, capsular stretching and soft tissue infiltration.

dexamethasone 4mg 15mg daily oral, S/C, I/Vprednisolone 25mg daily oral

6.5 Ketamine (refer to Pain or Palliative Care Services)Probable role in neuropathic or chronic cancer pain

NMDA receptor antagonist

used in subanaesthetic doses eg 25 - 200mg per 24 hours appears to be compatible with morphine in a syringe driver for S/C use6.6 ClonidineFor anxiolytic and opioid sparing action. Clonidine may also prevent withdrawal effects during opioid changeover.

adrenergic agonist

dose range 150 - 300mcg daily continuous S/C infusion or 2 divided doses oral

compatible with morphine in syringe driver7. MANAGEMENT OF SIDE EFFECTS OF OPIOIDS

Opioids induce constipation in 95% of patients due to decreased intestinal secretions and reduced peristalsis. Regularprophylactic stool softener/peristaltic stimulant should be used e.g. Coloxyl with Senna. If possible the patient should bewell hydrated and active. Refer to RAH Guidelines For Prevention And Treatment Of Opioid-Induced Constipation.

Opioids induce nausea and vomiting in about 30% of patients. Regular antiemetics may be needed at commencement oftherapy. This side effect usually wears off in a few days.

Drowsiness is predictable when commencing morphine. It usually passes within a few days and should not preventregular administration or dose increment if necessary.

Dependence and respiratory depression are not a problem when the dose of opioid is titrated against the patients pain.

Tolerance is rarely a significant clinical problem. Dose escalation may be required if pain increases.

Pruritus occurs occasionally with systemic opioids. The mechanism is poorly understood and currently recommendedtreatments are usually ineffective. Opioid rotation should be considered.

8. PATIENT EDUCATIONMany patients are reluctant to take regular analgesia, particularly morphine. This often involves a number of fears, including

fear that there will be nothing left for the end

fear of addiction to morphine

fear that if they use morphine it must mean the end is near.Education, counselling and reinforcement by the health care team is important to allay concerns of the patient and family.

Revised 2001


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PLEURODESIS

DETAILS OF PROCEDURE:

(a) Complete drainage of pleural space by a (24Fr Argyle catheter) inserted in the 6th-7thintercostal space in the posterior axillary line and connected to an underwater seal drain.

(b) When drainage is completed (shown by chest X-ray), the following substances in order areinstilled into the pleural space using a 23 gauge needle injected tangentially through thedrainage tubing:-

(i) 5 ml of 1% Lignocaine(ii) Steritalc-F, 100ml dispersion

orBleomycin 60 units

(iii) 200 ml of air.

(c) The tube is clamped for 2 hours (in the absence of a bronchopleural fistula). During this timethe patient is instructed to rotate through prone, supine, right and left lateral positions at 30minute intervals.

(d) At the end of 2 hours the tube is unclamped for approximately 48 hours until drainage is lessthan 150mls/24 hours for 2 consecutive days.

(e) Careful nursing observation is implemented according to procedure in S2 using intercostaldrain nursing chart.

(f) If, after 48 hours, there has been no evidence of an irritative response (temperature, tachycardiafor 12-24 hours) or the drainage is still greater than 150 mls/24 hours, a repeat instillation oftalc is given as above.

(g) The tube is removed and the procedure is complete provided the repeat chest x-ray examinationindicates that the lung is appropriately expanded.

(h) Follow up chest x-ray at 2-3 weeks.


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POST-MENOPAUSAL SYMPTOM MANAGEMENT

Oestrogen used alone (oestrogen replacement therapy) or with the addition of progesterone (Hormonereplacement therapy HRT) is known to be effective in reducing menopausal symptoms including hotflushes, vaginal dryness and urinary symptoms. Oestrogen is also beneficial in preventing osteoporosisand less certainly cardiovascular disease. Concerning use in women with a prior diagnosis of breastcancer, there are basic scientific data but little methodologically strong observational data, and nonefrom randomised studies.

Alternatives for menopausal symptoms include:

KY Jelly (or similar) for vaginal dryness and local menopausal symptoms

venlafaxine for hot flushes - starting dose 37.5mg daily gradually increasing to 75mg daily if noteffective (higher doses produce more side effects) (currently non-PBS and non-Formulary forthis indication)

Alternatives the prevention of osteoporosis include:

calcium supplements, bisphosphonates, diet and exercise,

Alternatives for cardiovascular disease include:

diet, exercise and statins.

References:Pritchard KI. Hormone replacement in women with a history of breast cancer. Oncologist. 2001;6(4):353-62.

Barton D, La VB, Loprinzi C, Novotny P, Wilwerding MB, Sloan J. Venlafaxine for the control of hot flashes: results of a longitudinalcontinuation study. Oncol Nurs Forum. 2002 Jan-Feb;29(1):33-40.Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, ChristensenBJ. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000 Dec

16;356(9247):2059-63.


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PRURITUS

For itch associated with skin irritation or allergy a trial of sedating antihistamines is recommended.

e.g.

Promethazine 10 to25mg every 6 hoursOrHydroxyzine 25 to 50mg every 6 to 8 hours

For itch associated with cholestasis

(1) Cholestyramine 1 sachet (4g) qid.

If this is unsuccessful

(2) Rifampicin 150 to 300 mg bd.

Reference:Price TJ, Patterson WK, Olver IN. Rifampicin as treatment for pruritis in malignant cholestasis. Support Care Cancer, 1998, 6: 533-535.Connolly C S; Kantor G R; Menduke H Hepatobiliary Pruritus: What Are Effective Treatments?J Am Acad Dermatol, vol 33, iss 5I, p 801-

805, yr 1995


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SPERM COLLECTION & STORAGEREPRODUCTIVE MEDICINE UNITThe University of Adelaide, The Queen Elizabeth Hospital

INFORMATION STATEMENT ON THE CRYOPRESERVATION AND STORAGE OF SPERMPrepared in accordance with the Code of Ethical Clinical Practice (Reproductive Technology Act, 1988)

Sperm can be cryopreserved (frozen) and stored in liquid nitrogen at - 196oC for may years.

The effectiveness of sperm cryopreservation is quite variable, however, and there is no guarantee that the sperm will survivethawing. There is also no guarantee that the thawed sperm will be fertile or that they will give rise to a conception if they areused in conjunction with reproductive technologies such as artificial insemination, in vitro fertilization and spermmicroinjection.

Before we cryopreserve your sperm, we may ask you to undergo a blood test to check for infectious diseases such as HIV(the AIDS virus), syphilis and hepatitis. This is merely a precaution against cross-infection from one sample to anotherduring storage. If these tests have recently been done, then we wont repeat them and we will obtain the results from yourdoctor.

If you are infected with hepatitis, we will store your frozen sperm in a separate container which also contains sperm fromother men who are infected with hepatitis. We do not routinely store sperm from men who carry infectious diseases such asHIV.

Semen Collection:

The procedure for semen collection will be explained to you by one of the laboratory staff. A separate information statementis also available.

It is important that you do not ejaculate for at least 2 days (ideal period is 3-7 days) prior to the collection of each semensample so that the best sample is stored each time.

It is usually advisable to store more than one sample so that enough semen is available for future use. However, this alsodepends on your semen quality and the reason for storage - the laboratory staff will advise you on the number of samples. If

you are concerned about the cost of storing more than one sample, bear in mind that the recommended number of sampleswill enable us to consider the most suitable treatment option(s) if you need to use the frozen semen.

Please make an appointment for each sample. Phone the Andrology Laboratory on (08) 8222 6827.

Sperm Cryopreservation and Storage:

After collection, the semen will be analysed, mixed with a solution to reduce the freezing damage and then frozen in colour-coded, labelled plastic straws and stored at -196oC in a tank containing liquid nitrogen. The semen analysis andcyropreservation results will be sent to your doctor.

While all reasonable care will be taken during the handling, cyropreservation and storage of sperm, there is a slight risk ofdamage to or loss of viability of the sperm.

If the semen is frozen at a site other than The Queen Elizabeth Hospital, it may be necessary to transfer it to the ReproductiveMedicine Unit at The Queen Elizabeth Hospital for long term storage. And in the future, it may be necessary to transfer itbetween the Reproductive Medicine sites and/or other sites. There is a slight risk of damage to or loss of the frozen spermduring such transfers.LEGAL REQUIREMENTS:The Reproductive Technology Act (1988) sets guidelines on sperm storage. A copy of the Act, the regulations under the Act,and the standards and codes of practice adopted by or referred to in the regulations are available for inspection during normalworking hours at the Reproductive Medicine Units. There is no charge for inspection.The Act requires that a consent form is signed prior to sperm cyropreservation, and that anyone who give consent for spermcyropreservation and storage under the Code of Ethical Clinical Practice is entitled to a copy of the signed consent form.

Consent may be revoked at any time by notice in writing to the Head of the Reproductive Medicine Unit. If consent isrevoked, the Reproductive Medicine Unit will dispose of the frozen sperm.


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The Head of the Reproductive Medicine Unit may require personal information to be provided in order to comply with theAct or the Code of Ethical Clinical Practice and must ensure that confidential information kept by the ReproductiveMedicine Unit is disclosed only as authorised by the Act or the Code of Ethical Clinical Practice. If the Head of theReproductive Medicine suspects that confidential information has been disclosed in breach of the Act or the Code of EthicalClinical Practice, he/she must investigate and submit a written report to the South Australian Health Commission (and to theCommissioner of Police if there is suspicion that an offence has been committed).

A person in relation to whom the Head of the Reproduction Medicine Unit keeps a record may consent to the disclosure ofany information in that record relating to his or her personal affairs.

Cost of Sperm Cryopreservation and StorageA standard semen analysis fee is charged for analysing EACH semen sample - this is covered by Medicare and will either bebulk-billed directly to Medicare or you will be sent an account.

There is an additional $50.00 fee PER SAMPLE for cyropreservation and storage for up to 12 months. At the end of 12months, and again every 12 months thereafter, a storage of $100.00 will be charged to cover continued storage of thesample(s) for up to 12 months.

The cyropreservation and annual storage fees are not covered by Medicare or private health insurance. Accounts will be

issued by the Reproductive Medicine Unit (Repromed Pty Ltd).

Public patients who are about to undergo chemotherapy or radiotherapy, and patients with a health care card (HCC), areeligible for 50% concessional rates on the cyropreservation and storage fees.

If you have difficulty paying the fees, please phone the Reproductive Medicine Unit Accounts Department on 08 8222 6782.We are happy to accept part payments until the full account is settled.

The FutureIt is your responsibility to inform the Reproductive Medicine Unit of any changes of address. Otherwise we wont be able tocontact you each year to obtain instructions regarding your frozen sperm.

If the fees are not paid or you cannot be contacted, the Reproductive Medicine Unit is under no obligation to

continue storage and the frozen sperm may be discarded.

You are welcome to discuss sperm cyropreservation or your future fertility with the medical staff and/or counsellor of theReproductive Medicine Unit. Ask the laboratory staff for assistance.

If you are having chemotherapy, radiotherapy or surgery which might impair your fertility, it is advisable to have a follow-upsemen analysis to determine the long term effect of the treatment on your sperm production. This should be done about 2years after the finish of chemotherapy or radiotherapy.

Additional InformationTelephone the Andrology Laboratory at the Queen Elizabeth Hospital on (08) 8222 6827

Account enquiries should be directed to the Repromed Accounts Department on (08) 8222 6782


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SYMPTOM CONTROL - TERMINAL CARE

TERMINAL RESTLESSNESS

Midazolam - 2.5-10 mg subcutaneous 2-4 hourly or10-30 mg per 24 hours subcutaneous infusion

Diazepam - 5-10 mg oral or rectal

TERMINAL RESPIRATORY CONGESTION (or Death Rattle)Hyoscine - 0.4-0.8 mg subcutaneous 2-4 hourly prnAtropine - 0.3-0.6 mg subcutaneous 2-4 hourly prn

DEHYDRATION (symptomatic)Hypodermoclysis i.e. subcutaneous fluidsUse normal saline 500 ml - 2L per 24 hours

COUGH/BREATHLESSNESS

Morphine mixture - 2.5-5 mg 4-6 hourlyPholcodine Linctus

If above fails trymethadone 2.5 mg at night - up to 2.5mg b.d.nebulized morphine - 5-20 mg in 5 mls normal salinenebulized lignocaine - 1-2% 5 mls

Recent data suggest nebulized normal saline 5 mls is as effective as nebulized morphine for manypatients.ANOREXIA:

Loss of appetite frequently causes anxiety and tension between patient and family.Acknowledgment of the problem and reassurance may help.

Steroids may stimulate appetite in the short terme.g. Prednisolone 15-25mg orally

Dexamethasone 1-4 mg orally daily

Look for and treat correctable causese.g. Oral Candidiasis

Topical

Nystatin suspension 1-4mls 4-6 hourlyMiconazole oral gel spoonful 4-6 hourly

SystemicFluconazole 50 mg daily (available only on advice from Infectious Diseases Unit)If patient has dentures these should be soaked in 0.5% chlorhexidine overnight, then applynystatin ointment 100,000 U/ml (ad lib) to mucosal surface before reinsertion.

Anorexia may indicate underlying nausea and anti-emetic, eg. Metoclopramide, may be helpful.INTESTINAL OBSTRUCTION:

Nasogastric tubes are avoided where possible.

Try nil orally, ice chips. Avoid the oral route for analgesics and other medications

Hypodermoclysis should be considered for thirst e.g. N Saline 1 Litre SC over 8-12 hours.

Symptoms caused by the intestinal obstruction are identified and treated eg.


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pain - S/C morphinecolic - S/C Hyoscine butylbromide (Buscopan) 20-80 mg/24 hoursnausea -S/C Haloperidol 5-10 mg/24 hoursThese three drugs can all be combined in a S/C infusion.

Metoclopramide and other pro-kinetic drugs are not usually recommended once the bowel is

obstructed. Other anti-emetics that can be useful:- Hyoscine hydrobromide 400-800mcg/24 hours S/C

Prochlorperazine suppositories 25mg/6-8 hourly PR

Chlorpromazine suppositories 100mg mg/6-8 hourly PR

A short course of Dexamethasone - dose range 8-6mg/24 hours S/C which acts possibly by reducingbowel wall or tumour oedema, is worth considering,

For intractable vomiting percutaneous endoscopic gastrostomy (PEG) as a venting procedure is veryuseful

Reference:Ashby MA., Game PA, Devitt P, Britten-Jones R, Brooksbank MA, Davy MLJ, Keam E. Percutaneous gastrostomy as a venting procedure

in palliative care. Palliative Medicine 1991, 5: 147-150).


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TUMOUR LYSIS SYNDROME

1. Characteristic biochemical disturbances K+ Uric acid

PO4

Ca++

Lactic acidosis

2. The likelihood of developing acute tumour lysis can be predicted by:

Bulky disease

Marked sensitivityu of tumour ro Rx modality

Pre-existing renal impairment

Raised LDH (pretreatment >1500)

Raised uric acid

Mild Moderate SevereAllopurinol Allopurinol Allopurinol

+ +Hydration Hyperhydration

3. Corrective Action

Uric acid PO4 K+ Fluid overloadAlkalinizationDialysis

Fluids+DiureticStop AlkalinizationDialysis

Monitor ECGFluids + DiureticResonium/ Insulin glucoseCa GluconateAlkalinizationDialysis

DiureticDialysis

Allopurinol

300mg/day. May give loading dose of 600 mg daily for 2-3 days in high risk patients with normal renalfunction. Need dose reduction in renal impairment in relation to creatinine clearance.

Hyper-hydration3 litres /m2/day with NS or1/5 NS continued till the period of risk is over , as judged by stablebiochemical indices and decrease in assessable disease. Aim to keep urine output > 100ml/hour

Hydration1.5 litres/m2/day orally or intravenously

Alkalinization

50-100 Meq NaHCO3 /litre of hydration fluid, aiming for urine PH 7.0-8.0 (note: uric acid is 13x moresoluble at PH 7 than PH 5 ); Yet alkalization can exacerbate nephrocalcinosis associated withhyperphosphataemia.

Insulin - Glucose10 units of Actrapid in 50 ml D50 over 30 minutes. Avoid if haemodialysis can be arranged within hour.

Haemodialysis:For progressive renal failure or rapidly deteriorating metabolic disturbances

Reference:RC Chasty, JA Liu-yin. Acute tumour lysis syndrome Br J Hosp Med 1993;49:88-492


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SECTION TWO

CHEMOTHERAPY PROTOCOLS


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ANAL CANCER:Combined chemotherapy/radiotherapy

Chemot

Chemotherapy Guidelines Adelaide

Documents

Transcript of Chemotherapy Guidelines Adelaide