I N D E X Page. Relapse Regimens 8. Methotrexate-40 IV CTIS Docetaxel-75 CTIS Mr M. Gilhooly Date: Review date: July 2012

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1 UPPER AERODIGESTIVE TRACT CANCERS Section by: Dr Simon Stewart and Dr Sarah Partridge Version; Upper Aerodigestive Tract v4.1 NWLCN 16Jun11 Section last updated: 16 th June 2011 Section last corrected 16 th June2011 Approved by Oncology UAT Lead Dr S. Stewart Date: Approved by NWLCN UAT TWG Mr M. Gilhooly Date: Review date: July 2012 I N D E X Page Chemotherapy Alone First Line 1. Cisplatin20 x 5dy/5FU1200 x4day CIS20/5FU 1200 CTIS Carbo 5AUC/5FU1200 x 4day CARBO/5FU 1200 CTIS Cisplatin75/5FU 1000 x 4day CIS75/5FU1000 CTIS Docetaxel/5FU/Cisplatin DOCE-5FU-CISP CTIS Docetaxel/Cisplatin-IP DOCE-CISP-IP CTIS Chemo-Radiation 6a. Cisplatin-100 D1+22+RT (1 day) CIS100+RT D1+22 CTIS b. Cisplatin-50 D1+22+RT (2 day) CIS50+RT D1+22 CTIS c. Cisplatin-25 D1+22+RT (4 day) CIS25+RT D1+22 CTIS Cetuximab Single Agent CTIS 1249, Relapse Regimens 8. Methotrexate-40 IV CTIS Docetaxel-75 CTIS UAT Regimens doc UAT Page 1 of 15

2 UPPER AERODIGESTIVE TRACT CANCERS Section by: Dr Simon Stewart and Dr Sarah Partridge Version; Upper Aerodigestive Tract v4.1 NWLCN 16Jun11 Section last updated: 16 th June 2011 Section last corrected: 16 th June 2011 Approved by Oncology UAT Lead: July 2011 Approved by NWLCN UAT TWG Julu 2011 Review date: July 2012 Chemotherapy Alone First Line 1. Cisplatin 20/5FU day (CTIS: 717) Pre-hydrations - Days 1 to 5 Cisplatin 20mg/m 2 IV over 2 hours Days 1 to 5 Post hydration Days 1 to 5 5-Fluorouracil 1200mg/m 2 /day* IV over 24 hours Days 1 to 4 Start 5FU at same time as prehydrations day 1. *5FU dose may be given as 1000mg/m 2 /day days 1 to 5 Interval between cycles: Repeat every 21 days Number of cycles: Up to 6 cycles Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA, ECG Tests to Ok/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs Crcl (calculated) redo EDTA if rising serum creatinine High risk antiemetics as per NWLCN Mouthcare directed by Head & Neck Clinic Additional information: Administration notes: Hydration and cisplatin can be infused at the same time as 5-FU. Maintain fluid output over 100ml/hour during and for 6-8 hours after cisplatin administration. Alternatively, weigh patient prior to and after cisplatin infusion. If weight gain is greater than 1.5kg, or patient is symptomatic of fluid retention, contact medical team for diuretic. Encourage patients to drink 2-3 litres of fluid following cisplatin. Stop infusion of 5FU if chest pain occurs and consult medical team. Patient information: Dose modifications: Table Cisplatin page 3 Chemotherapy treatment booklet (local information/macmillan) UAT Regimens doc UAT Page 2 of 15

3 Table Cisplatin UAT Side effect Cisplatin UAT Haematology Neutrophils Platelets x10 9 /L x10 9 /L 1.5 and 100 <1.5 or <100 Renal Function (NLCN 2009) Crcl 60mls/min 45-59mls/min <45mls/min Dose Modification Full dose Do not give. Discuss with consultant Full dose Cisplatin: 25% dose reduction Do not give cisplatin, consider carboplatin 2. CARBO/5FU day (CTIS: 339) Carboplatin 5(GFR+25)mg IV over 1 hour Day 1 5-Fluorouracil 1200mg/m 2 /day* IV over 24 hours Days 1 to 4 *5FU dose may be given as 1000mg/m 2 /day days 1 to 5 (CTIS: ) Interval between cycles: Repeat every 21 days Number of cycles: Up to 6 cycles Tests before starting course of chemo: FBC, U&Es, LFTs, EDTA Tests to OK/Confirm each cycle of chemo: FBC, U&Es, LFTs, Crcl (calculated). Redo EDTA if rising serum creatinine High risk antiemetics as per NWLCN Mouthcare directed by Head & Neck clinic Additional information: Administration notes: Stop infusion of 5FU if chest pain occurs and consult medical team. Dose modifications: Discuss with consultant 3. Cisplatin 75/5FU day (CTIS: 118) Pre hydrations Day 1 Cisplatin 75mg/m 2 IV over 2 hours Day 1 Post hydrations Day 1 5-Fluorouracil 1000mg/m 2 /day* Via infusor Days 1 to 4 *May increase dose to 1200mg/m 2 /day days 1 to 4 to achieve dose intensity of regimens 1&2 above Interval between cycles: Repeat every 21 days Number of cycles: Up to 6 cycles Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA, ECG Tests to Ok/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs, Crcl (calculated). Redo EDTA if rising serum creatinine UAT Regimens doc UAT Page 3 of 15

4 Patient information: UAT Regimens doc UAT Page 4 of 15 Very high risk antiemetics as per NWLCN Mouthcare directed by Head & Neck clinic Chemotherapy treatment booklet (local information/macmillan) Additional information: See notes for CIS20/5FU-1200 (CTIS 717) page 2 Dose modifications: Table Cisp page 3 4 DOCE-CISP-5FU (CTIS: 1357) Dexamethasone 8mg Oral BD For 3 days starting the day before docetaxel Docetaxel 75mg/m 2 IV over 1 hour Day 1 Pre hydrations Day 1 Cisplatin 75mg/m 2 IV over 2 hours Day 1 Post hydrations Day 1 5-Fluorouracil 750mg/m 2 IV over 24 hours Days 1 to 5 Interval between cycles: Repeat every 21 days Number of cycles: Good performance status induction chemotherapy or metastatic disease Up to 6 cycles Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA, ECG Tests to Ok/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs, Crcl (calculated). Redo EDTA if rising serum creatinine Very high risk antiemetics as per NWLCN Dexamethasone pre-medication used to reduce incidence and severity of fluid retention and severity of hypersensitivity reactions. Consider PPI (eg. lansoprazole) during dexamethasone administration as per local policy. Ciprofloxacin 500mg oral BD days 5 to 14 Mouthcare directed by Head & Neck clinic. If secondary prophylaxis with GCSF is required, consider Pegfilgrastim according to local policy. Additional information: Administration notes: Docetaxel Make sure patient has taken oral dexamethasone pre-medication at home/on ward (to reduce the risk of fluid retention and hypersensitivity reaction).

5 Patients should be observed closely, especially during the first 2 treatments, because of risk of anaphylaxis. Inform prescriber if patient reports any abnormal sensation which may be indicative of drug-induced neuropathy. Mucositis may be a problem with docetaxel, advise patients accordingly on mouth care Docetaxel Hypersensitivity Reactions Docetaxel may cause allergic reactions, see SPC information below. If any reaction occurs: stop infusion and discuss with consultant. After discussion with consultant: Mild reactions: eg. rash: May consider re-challenge after discussion with consultant Severe reactions: Do not re-challenge, discuss with consultant. Docetaxel reactions (SPC Sanofi-Aventis 24 August 2010): Patients should be observed closely for hypersentivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised cutanous reactions do not require interruption of therapy. However, severe reactions, such as severe hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions should not be re-challenged with docetaxel. Cisplatin/5FU Hydration and cisplatin can be infused at the same time as 5-FU. Maintain fluid output over 100ml/hour during and for 6-8 hours after cisplatin administration. Alternatively, weigh patient prior to and after cisplatin infusion. If weight gain is greater than 1.5kg, or patient is symptomatic of fluid retention, contact medical team for diuretic. Encourage patients to drink 2-3 litres of fluid following cisplatin. Stop infusion of 5FU if chest pain occurs and consult medical team. Dose modifications: Table below Table Doce-5FU-Cisp Head & Neck Side-effect: Doce-5FU-Cisp Renal Function Crcl 60mls/min 45-59mls/min <45mls/min Dose Modification (Source: SPC/S.Stewart) full dose Cisplatin: 25% dose reduction Do not give cisplatin, consider carboplatin UAT Regimens doc UAT Page 5 of 15

6 Side-effect: Doce-5FU-Cisp Haematology Neutrophils Platelets x10 9 /L x10 9 /L 1.5 and 100 <1.5 or <100 Febrile neutropenia (N=<0.5) For more than 1 week OR Severe cumulative cutaneous reactions OR Severe peripheral neuropathy Hepatic Impairment (SPC) Bilirubin >ULN And/or ALT/AST >3.5xULN And ALP >6xULN Dose Modification (Source: SPC/S.Stewart) Full dose Delay until recovery. Discuss next cycle dose with consultant Docetaxel: Reduce dose from 75 to 60mg/m 2 If reactions continue at 60mg/m 2 discontinue Do not give docetaxel 5. DOCE-CISP IP (CTIS: 1358) Dexamethasone 8mg Oral BD For 3 days starting day before docetaxel Docetaxel 75mg/m 2 IV over 1 hour Day 1 Pre hydrations Day 1 Cisplatin 75mg/m 2 IV over 2 hours Day 1 Post hydrations Day 1 Interval between cycles: Repeat every 21 days Number of cycles: Good performance status induction chemotherapy or metastatic disease where 5FU contraindicated Up to 6 cycles Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA, ECG Tests to Ok/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs, Crcl (calculated). Redo EDTA if rising serum creatinine Very high risk antiemetics as per NWLCN Dexamethasone pre-medication used to reduce incidence and severity of fluid retention and severity of hypersensitivity reactions Ciprofloxacin 500mg oral BD days 5 to 14 Mouthcare directed by Head & Neck clinic UAT Regimens doc UAT Page 6 of 15

7 Additional information: Administration notes: Docetaxel Make sure patient has taken oral dexamethasone pre-medication at home/on ward (to reduce the risk of fluid retention and hypersensitivity reaction). Patients should be observed closely, especially during the first 2 treatments, because of risk of anaphylaxis. Inform prescriber if patient reports any abnormal sensation which may be indicative of drug-induced neuropathy. Mucositis may be a problem with docetaxel, advise patients accordingly on mouth care. Docetaxel Hypersensitivity Reactions Docetaxel may cause allergic reactions, see SPC information on page 5 If any reaction occurs: stop infusion and discuss with consultant. After discussion with consultant: Mild reactions: eg. rash: May consider re-challenge after discussion with consultant Severe reactions: Do not re-challenge, discuss with consultant. Cisplatin Maintain fluid output over 100ml/hour during and for 6-8 hours after cisplatin administration. Alternatively, weigh patient prior to and after cisplatin infusion. If weight gain is greater than 1.5kg, or patient is symptomatic of fluid retention, contact medical team for diuretic. Encourage patients to drink 2-3 litres of fluid following cisplatin. Stop infusion of 5FU if chest pain occurs and consult medical team. Dose modifications: Table Doce-5FU-Cisp page 4 UAT Regimens doc UAT Page 7 of 15

8 Chemo-Radiation Regimens 6. Cisplatin with Radiotherapy Cisplatin administered weeks 1 and 4 of a six week course of radiotherapy using one of the three regimen below. 6a. Cisp100 D1+22+RT (CTIS: 770) 1 day regimen Pre hydrations Day 1 and 22 Cisplatin 100mg/m 2 IV over 2 hours Day 1 and 22 Post hydrations Day 1 and 22 Repeat: No repeats 1 cycle only. Chemo administered with fractions 1 and 15 (Day 1 and 22) of a 6 week cycle of radiotherapy. For post nasal space may administer an additional dose on day 42 Interval between cycles: No repeats Number of cycles: 1 cycle only. No repeats Tests before starting course of chemo: FBC, U&Es, Mg, LFTs EDTA Tests to OK/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs Crcl (calculated), redo EDTA if creatinine is rising Very high risk antiemetics as per NWLCN Mouthcare directed by Head & Neck clinic Additional information: See page 7 Dose modification: See table Cisplatin page 3 6b. Cisp50+RT D1+22 (CTIS: 732) 2 day regimen Pre hydrations Days 1, 2, 22, 23 Cisplatin 50mg/m 2 IV over 2 hours Days 1, 2, 22, 23 Post hydrations Days 1, 2, 22, 23 Repeat: Chemo administered with fractions 1 and 15 (Day 1 and 22) of a 6 week cycle of radiotherapy. For post nasal space may administer additional doses on day 42 and 43 Interval between cycles: No repeats Number of cycles: 1 cycle only. No repeats. Prescribed if patient unable to tolerate cisplatin 100mg/m 2 Day 1 and 22 above Tests before starting course of chemo: FBC, U&Es, Mg, LFTs EDTA Tests to OK/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs Crcl (calculated), redo EDTA if creatinine is rising High risk antiemetics as per NWLCN Mouthcare directed by Head & Neck clinic UAT Regimens doc UAT Page 8 of 15

9 Additional information: See page 7 Dose modification: See table Cisplatin page 3 6c. Cisplatin-25 Day 1+22_RT (CTIS: 1756) 4 day regimen Pre hydrations Day 1 to 4 and Day 22 to 25 Cisplatin 25mg/m 2 IV over 2 hours Day 1 to 4 and Day 22 to 25 Post hydrations Day 1 to 4 and Day 22 to25 Repeat: No repeats. 1 cycle only chemotherapy administered week 1 and week 4 of a 6 week cycle of radiotherapy. Interval between cycles: No repeats Number of cycles: 1 cycle only. No repeats. Prescribed if patient unable to tolerate cisplatin 100mg/m 2 day 1 and 22 or cisplatin 50mg/m 2 day 1,2,22 and 23 Tests before starting course of chemo: FBC, U&Es, Mg, LFTs EDTA Tests to OK/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs Crcl (calculated), redo EDTA if creatinine is rising High risk antiemetics as per NWLCN Mouthcare directed by Head & Neck clinic Additional information: Administration notes: See page 7 Dose modification: See table Cisplatin page 3 UAT Regimens doc UAT Page 9 of 15

10 7. Cetuximab In line with NICE for locally advanced squamous cell carcinoma of Head and Neck, where patient has Karnofsky performance status score is 90%, is suitable for radical radiotherapy but unsuitable for all forms of platinum based therapy. (NICE June 2008) Loading dose to be administered 7 days before radiotherapy. (CTIS: 1249) Chlorphenamine 10mg IV bolus dose Pre cetuximab Day 1 Dexamethasone* 8mg IV bolus dose Pre cetuximab Day 1 Cetuximab 400mg/m 2 IV over 2 hours Day -7 ie. 7 days before radiotherapy Maintenance dose administered 1 hour prior to radiotherapy (CTIS: 1250) Chlorphenamine 10mg IV bolus dose Pre cetuximab Day 1 Dexamethasone* 8mg IV bolus dose Pre cetuximab Day 1 Cetuximab 250mg/m 2 IV over 1 hour Days 1,8,15,22,29 *Dexamethasone dose reduced to 4mg cycle 2 onwards if no reaction to cycle 1 Repeat: Repeat every 7 days as detailed below. Cetuximab loading dose administered 7 days before radiotherapy starts. If start of radiotherapy is delayed, do not repeat loading dose provided radiotherapy commences within 1 month of loading dose. Cetuximab maintenance dose administered once a week, one hour before radiotherapy during a 5 week cycle of radiotherapy. Some patients may receive 7 weeks of radiotherapy in this case cetuximab is administered weekly for 7 weeks of radiotherapy (days 1,8,15,22,29,36 and 43) Interval between cycles: No repeats 1 cycle only Number of cycles: 1 cycle only in line with NICE Tests before starting course of chemo: FBC, U&Es, Mg, Ca, LFTs Tests to OK/Confirm each cycle of chemo: FBC, U&Es, Mg, Ca for 8 weeks after last dose, LFTs Low risk antiemetics as per NWLCN Chlorphenamine, dexamethasone, paracetamol and ranitidine to prevent infusion related reactions. Mouthcare by Head and Neck Clinic Doxycycline 100mg once a day General advice about EGFR Skin Reactions UAT Regimens doc UAT Page 10 of 15

11 Additional information: Administration notes: (SPC) Cetuximab: Close monitoring is required during and for at least 1 hour after the end of the infusion. Availability of resuscitation equipment must be ensured. Patients must receive premedication with antihistamine and corticosteroid prior to every cetuximab infusion. The first cetuximab infusion is infused over 2 hours. If well tolerated then subsequent infusions may be administered over 1 hour. If the patient experiences mild/moderate infusion related reactions consult the doctor as the infusion rate must be decreased. The maximum rate of infusion must not exceed 10mg/min. If cetuximab is administered in combination with other chemotherapy, the chemotherapy must be administered at least 1 hour after the end of the cetuximab infusion. Dose modifications: EGFR Related Skin Reactions General advice: Sun: Dry Skin: Advise patient to avoid sun and use sun-block Use oil for washing instead of soap Avoid hot water for baths/shower Emollient creams help Topical corticosteroid creams NOT recommended Fissures may occur in dry skin and topical dressings eg. hydrocolloid dressings as advised by dermatologists are helpful Pruritis; Consider oral antihistamines Nail toxicity: Seek dermatological advice Daily salt baths and local antiseptic/astringent ointments have been found to be helpful Anti-inflammatory drugs may help to ease the pain Dose modifications: Table: Cetuximab Head & Neck Side-effect Haematology Cetuximab has not been studied in patients presenting with one or more of the following laboratory parameters: Haemoglobin <9g/dl Leukocyte count <3.0 x 10 9 /L Absolute neutrophil count <1.5 x 10 9 /L Platelet count <100 x 10 9 /L Renal Function Serum creatinine > 1.5 x ULN Hepatic Function Very common elevated mild to moderate increase in liver enzyme levels (ASAT, ALAT, AP). If transaminases >5 x ULN And/or Bilirubin > 1.5 x ULN UAT Regimens doc UAT Page 11 of 15 Dose Modification (Source: SPC) Do not treat unless FBC parameters are above these levels. SPC states only patients with adequate renal function have been investigated to date Discuss with consultant in charge if serum creatinine >1.5 x ULN SPC states: Only patients with adequate hepatic function have been investigated to date (transaminases 5 x ULN, bilirubin 1.5 x ULN). Discuss with consultant in charge

12 Side-effect Elderly No dose adjustment is required in the elderly, but there is only limited experience in patients over 75 years of age Mucositis Very common Skin Toxicity Dose Modification (Source: SPC) Discuss with consultant in charge Discuss with MDT in the Head & Neck radiotherapy on treatment clinic General Information (SPC) Skin reactions may develop in more than 80% of patients and mainly present as acne-like rash and/or less frequently as pruritus, dry skin, desquamation or nail disorders (eg. paronychia). Approximately 15% of skin reactions are severe including single cases of skin necrosis. The majority of skin reactions develop within the first 3 weeks of therapy. They generally resolve, without sequelae over time following cessation of treatment if the recommended adjustments in dose are followed. Skin lesions induced by cetuximab may predispose patients to suprainfections (eg. S Aureus) which may lead to subsequent complications eg. cellulitis, erysipelas or potentially with fatal outcome, staphylococcal scalded skin syndrome or sepsis. Nail Toxicity (COIN B) Nail toxicity occurs in 8% of patients with cetuximab characterised by paronychial inflammation with associated swelling of the lateral skin folds of toes and fingers, especially big toes and thumb which may be painful. This may persist for up to 12 weeks after cessation of cetuximab. Skin Toxicity (Dr Stewart) NCI-CTC Grade 1 acneform eruption If skin reactions occur within the field of radiation, stop Cetuximab until reaction resolved. If skin reaction occurs outside of radiation field discuss with consultant. Nail problems Electrolyte Disturbances (SPC) Magnesium (up to 65% of patients) <0.6mmol/L Hypokalaemia Refer to dermatologist (see general advice page 41) Correct electrolyte depletions as appropriate Progressively decreasing serum magnesium levels occur frequently and may lead to severe hypomagnesaemia which may last up to 8 weeks after the last dose. Hypomagnesaemia is reversible following discontinuation of cetuximab. Correct by intravenous supplementation if symptomatic or <0.4mmol/L (grade 3). Lesser degrees of hypomagnesaemia may be corrected with oral magnesium glycerophosphate. May develop as a consequence of diarrhoea Hypocalcaemia UAT Regimens doc UAT Page 12 of 15 May occur. In combination with platinum-based chemotherapy, the frequency of severe hypocalcaemia may be increased

13 Side-effect Hypersensitivity Reactions (Erbitux Dosage, Preparation and Administration Guide ZZ30054 Merck Oncology July 2004) Grade 1 (transient rash, drug fever <38 o C) Grade 2 (Urticaria, drug fever 38 o C and/or asymptomatic bronchospasm) Grade 3 or 4 (Grade 3: symptomatic bronchospasms requiring parenteral medication, with or without urticaria; hypersensitivity-related oedema, angiodema) Grade 4: Anaphlyaxis Recurrent allergic/hypersensitivity reactions (Crystal) Dose Modification (Source: SPC) Decrease the cetuximab infusion rate by 50% and monitor closely for any worsening. The total infusion time for cetuximab should not exceed 4 hours (400mg/m 2 ) or 2 hours (250mg/m 2 ) respectively. Stop cetuximab infusion. Administer bronchodilators, oxygen etc as medically indicated. Once allergic/hypersensitivity reaction has resolved or decreased to grade 1 in severity resume infusion at 50% of previous rate and monitor closely for any worsening. Stop cetuximab infusion immediately and disconnect infusion tubing from the patient. Administer adrenaline/epinephrine, bronchodilators, antihistamines, glucocorticoids, intravenous fluids, vasopressor agents, oxygen etc as medically indicated. Patients have to be withdrawn immediately from the treatment and must not receive any further cetuximab treatment. Do not re-challenge with cetuximab If patient has a second allergic hypersensitivity reaction on the slower infusion rate, stop the cetuximab infusion and treat reaction. DO NOT re-challenge with cetuximab. UAT Regimens doc UAT Page 13 of 15

14 Upper Aeordigestive Tract Cancer Relapse Regimens 8. Methotrexate-40 IV (CTIS: 1029) Methotrexate 40mg/m 2 IV bolus Day 1 Interval between cycles: Repeat every 7 days Number of cycles: Continues depending on response/toxicity. Often weekly for 6 weeks then 2 weeks off, then repeat Tests before starting course of chemo: FBC, U&E, LFTs Tests to OK/Confirm each cycle of chemo: FBC, U&Es, LFTs Low risk antiemetics as per NWLCN Mouthcare as directed by Head & Neck clinic. ) Additional information: Dose modifications: See table below Table: Mtx UAT Side-effect Mucositis Grade 0-1 Grade 2 Grade 3 Dose Modification Full dose Delay until recovery Delay until recovery then methotrexate 20% dose reduction 9. Docetaxel-75 (CTIS: 1360) Dexamethasone 8mg Oral BD For 3 days starting the day before Docetaxel 75mg/m 2 IV over 1 hour Day 1 Interval between cycles: Repeat 21 days Number of cycles: After failure of Cisplatin/5FU and Methotrexate: 6cycles Tests before starting course of chemo: FBC, U&Es, LFTs, Tests to OK/Confirm each cycle of chemo: FBC, U&Es, LFTs, weight (check fluid retention) High risk antiemetics as per NWLCN guidelines or as per local policy. Dexamethasone pre-medication used to reduce incidence and severity of fluid retention and severity of hypersensitivity reactions. Consider PPI cover if appropriate. Mouthcare as directed by Head & Neck Clinic UAT Regimens doc UAT Page 14 of 15

15 Additional information: Administration notes Make sure patient has taken oral dexamethasone pre-medication at home/on ward (to reduce the risk of fluid retention and hypersensitivity reaction). Patients should be observed closely, especially during the first 2 treatments, because of risk of anaphylaxis. Inform prescriber if patient reports any abnormal sensation which may be indicative of drug-induced neuropathy. Mucositis may be a problem with docetaxel, advise patients accordingly on mouth care. Docetaxel Hypersensitivity Reactions Docetaxel may cause allergic reactions, see SPC information on page 5 If any reaction occurs: stop infusion and discuss with consultant. After discussion with consultant: Mild reactions: eg. rash: May consider re-challenge after discussion with consultant Severe reactions: Do not re-challenge, discuss with consultant. Dose modifications: See table below Table Docetaxel-75 UAT Side effect Docetaxel-75-UAT Haematology Neutrophils Platelets x10 9 /L x10 9 /L 1.5 and 100 <1.5 or <100 Febrile neutropenia (N=<0.5) For more than 1 week OR Severe cumulative cutaneous reactions OR Severe peripheral neuropathy Dose Modification (SPC) Full dose Delay until recovery. Discuss next cycle dose with consultant Docetaxel: Reduce dose from 75 to 60mg/m 2 If reactions continue at 60mg/m 2 discontinue Hepatic Impairment (SPC) Bilirubin >ULN And/or ALT/AST >3.5xULN And ALP >6xULN Do not give docetaxel UAT Regimens doc UAT Page 15 of 15