Network Chemotherapy Regimens - Minervation Ltd · 2014-03-15 · Mitoxantrone Prostate 10 Docetaxel Prostate 11 Docetaxel Weekly Advanced Prostate 12 CMV Bladder 14 Gemcitabine

Thames Valley Cancer Network

Network Chemotherapy Protocols – Urological Cancer 1

Network Chemotherapy

Regimens

Urological Cancer



Notes from the editor These protocols are available on the Network website www.tvcn.nhs.uk. Any correspondence about the protocols should be addressed to: Sally Coutts, Lead Pharmacist, Thames Valley Cancer Network email: [email protected] Tel : 01865 857166 Acknowledgements These protocols have been compiled by the Network Pharmacy Group in collaboration with the Urology TSSG with key contribution from Karen Carter, Senior Oncology Pharmacist, RBFT Dr Andrew Protheroe, Consultant Oncologist, OUH Dr Nicola Stoner, Principal Oncology Pharmacist, OUH Sandra Harding- Brown, Formerly Specialist Principal Pharmacist, Cancer Directorate, OUH Alison Ashman, Formerly Lead Pharmacist Thames Valley Cancer Network

© Thames Valley Cancer Network. All rights reserved. Not to be reproduced in whole or in part without the permission of the copyright owner.

http://www.tvcn.nhs.uk/



Network Chemotherapy Regimens Urological Cancer

Network Chemotherapy Protocols approved for use within the Thames Valley Cancer Network by the Urology TSSG Date published: October 2012 Date of review: October 2014

Chemotherapy Protocols

Name of protocol Indication Page

List of amendments to this version 5

Abiraterone Prostate 6

Cabazitaxel Prostate 8

Mitoxantrone Prostate 10

Docetaxel Prostate 11

Docetaxel Weekly Advanced Prostate 12

CMV Bladder 14

Gemcitabine / Cisplatin Bladder 16

Gemcitabine / Carboplatin Bladder 18

MVAC Bladder 20

MVAC accelerated Bladder 22

BEP 3 day (adjuvant) Non-seminomatous germ cell tumour 24

BEP 3 day (metastatic) Non-seminomatous germ cell tumour 26

BEP 5 day metastatic) Non-seminomatous germ cell tumour 28

Carboplatin AUC 7 Non-seminomatous germ cell tumour 31

Paclitaxel / ifosfamide / cisplatin (TIP) Salvage therapy 32

POMB / ACE Germ cell 36

PEC Relapsed germ cell 39

EP (seminoma) Seminoma 41

BEP (3 day) Adenocarcinoma of unknown primary 43

Axitinib Renal cell 45

Everolimus Renal cell 47

Interferon (Roferon) Renal cell 49

Pazopanib Renal cell 50

Sunitinib Renal cell 52



Name of protocol Indication Page

Mitomycin C bladder installation weekly Bladder 54

Mitomycin C bladder installation 14 day Bladder 55

Mitomycin C bladder installation post op Bladder 56

BCG bladder installation Bladder 57

Pre and post hydration 58

Common toxicity criteria 59



List of amendments in this version Protocol type: Urology Tumours Date due for review: October 2014 Previous Version number: 3.1 This version number: 3.2 Table 1 Amendments

Page Action

Type Amendment Made/

asked by

All Dose modifications updated

All Cisplatin inpatient duration removed

Table 2 New protocols to be approved and or checked by TSSG included in this version

Name of protocol Indication Reason / Proposer

Abiraterone Prostate cancer NICE approved

Cabazitaxel Prostate cancer CDF

Everolimus Kidney CDF



ABIRATERONE (Prostate) Indication: Advanced or metastatic castration resistant prostate cancer, previously treated with docetaxel, with PSA and / or radiographic evidence of disease progression.

DRUG REGIMEN Day 1 Abiraterone 1000mg orally once daily Prednisolone 5mg orally twice daily Cycle Frequency: Daily until progression

DOSE MODIFICATIONS Abiraterone: Any dose modifications should be discussed with a Consultant.

Renal impairment No dose adjustment necessary. Caution advised in patients with severe renal impairment.

Hepatic impairment For patients who develop hepatotoxicity during treatment, suspension of treatment and dose adjustment may be required. No dose adjustment is required in pre-existing mild hepatic impairment. Moderate (Child-Pugh class B) give 250mg daily. Elevations in ALT or AST >5xULN or bilirubin >3xULN in patients with moderate hepatic impairment discontinue abiraterone. Abiraterone should be avoided in severe hepatic impairment.

INVESTIGATIONS Routine Blood test 1) Blood results required before drug administration

Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5

Blood tests should be performed 2 weekly for 3 months for transaminases, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) 2) Non urgent tests Tests relating to disease response/progression

Abiraterone Urology TSSG Chair Authorisation: Date:

Page 1 of 2 Published: October 2012 Review: October 2014

Version 3.2



CONCURRENT MEDICATION

ANTIEMETIC POLICY Minimal emetic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Hypertension, hypokalaemia and fluid retention use with caution Adrenocortical insufficency Hepatotoxicity REFERENCES SPC September 2011

Abiraterone Urology TSSG Chair Authorisation: Date:


Version 3.2



CABAZITAXEL (Prostate) Indication: 2nd line treatment of hormone refractory metastatic prostate cancer following docetaxel based therapy Ensure funding is available for each patient before prescribing.

DRUG REGIMEN Day 1 Cabazitaxel 25mg/m2 in 250ml sodium chloride 0.9% IV infusion over 1 hour Prednisolone 10mg orally daily Cycle Frequency: Every 21 days for 6 cycles

DOSE MODIFICATIONS Cabazitaxel: Hepatic impairment Cabazitaxel is extensively metabolised by the liver. As a precautionary measure, cabazitaxel should not be given to patients with hepatic impairment (bilirubin 1 x ULN, or AST and/or ALT 1.5 x ULN). Renal impairment Mild renal impairment (creatinine clearance (CLCR): 50 to 80 ml/min) no dose adjustment necessary. Moderate (CLCR: 30 to 50 ml/min) limited data available Severe renal impairment (CLCR <30 ml/min) or end stage renal disease treat with caution and monitor carefully during treatment. Dose modifications should be made if patients experience the following adverse reactions: Adverse reactions Dose modification Prolonged grade 3 neutropenia (longer than Delay treatment until neutrophil count is 1 week) despite appropriate treatment >1.5x109/L, then reduce cabazitaxel dose including G-CSF from 25 mg/m2 to 20mg/m2. Febrile neutropenia or neutropenic infection Delay treatment until improvement or resolution, and until neutrophil count is >1.5x109/L, then reduce cabazitaxel dose from 25 mg/m2 to 20 mg/m2.

Cabazitaxel Urology TSSG Chair Authorisation: Date:


Version 3.2



Grade >=3 diarrhoea or persisting diarrhoea Delay treatment until improvement or Despite appropriate treatment, including fluid resolution, then reduce cabazitaxel dose and electrolytes replacement from 25 mg/m2 to 20mg/m2. Grade >= 2 peripheral neuropathy Delay treatment until improvement, then reduce cabazitaxel dose from 25 mg/m2 to 20 mg/m2. The treatment should be discontinued if a patient continues to experience any of these reactions at 20 mg/m2.


Give Discuss

Hb x g/dL ≥10 < 10


. Creatinine Liver function tests (LFT) 2) Non urgent tests Tests relating to disease response/progression


ANTIEMETIC POLICY Low emetic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Hypersensitivity reactions Peripheral neuropathy REFERENCES SPC April 2011

Cabazitaxel Urology TSSG Chair Authorisation: Date:


Version 3.2



MITOXANTRONE (Prostate) Indication: Hormone refractory metastatic prostate cancer

DRUG REGIMEN Day 1 MITOXANTRONE 12mg/m2

IV in 50ml sodium chloride 0.9% infusion over 15 minutes Cycle Frequency: Every 21 days maximum 9 cycles

DOSE MODIFICATIONS Mitoxantrone: Bilirubin >60micromol/L and good performance status give 60% dose Bilirubin >60micromol/L and poor performance status omit Maximum cumulative dose = 110 mg/m2

INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Cardiac function if required. 2) Non-urgent tests Tests relating to disease response/progression

CONCURRENT MEDICATION Prednisolone 5mg bd (or 10mg od) orally continuously

ANTI-EMETIC POLICY Low emetogenic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cardiotoxicity – monitor cardiac function. Mitoxantrone may be stopped in future cycles if signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue.

REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic

impairment. 2009, The North London Cancer Network.

Mitoxantrone Urology TSSG Chair Authorisation: Date:


Version 3.2



DOCETAXEL Indications: Hormone refractory prostate cancer

NICE recommend docetaxel as a possible treatment for men with hormone-refractory metastatic prostate cancer.

DRUG REGIMEN Day 1 PREMEDICATION: DEXAMETHASONE

DOCETAXEL 75mg/m2

in 250ml sodium chloride 0.9% infusion over 1 hour

Cycle Frequency: Every 21 days maximum 10 cycles NB It is recommended that the treatment should be stopped at a MAXIMUM of 10 cycles, if adverse events occur or in the presence of disease progression.

DOSE MODIFICATIONS Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Hepatic impairment: Patients who have both elevations of transaminases (ALT and/or AST) > 1.5 x ULN and ALP > 2.5 x ULN: give 75% dose Patients with serum bilirubin > ULN and/or ALT and AST > 3.5 x ULN associated with ALP > 6 x ULN: docetaxel should not be used unless strictly indicated.


Give Discuss

Hb x g/dL ≥10 < 10


2) Non urgent tests. Tests relating to disease response/progression

CONCURRENT MEDICATION Prednisolone 5mg bd po continuously.

ANTIEMETIC POLICY Low emetogenic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Ensure pre-medication is given Dermatology – hand-foot syndrome

Docetaxel Urology TSSG Chair Authorisation: Date:


Version 3.2



DOCETAXEL weekly Indications: Advanced prostate cancer

NICE recommend docetaxel as a possible treatment for men with hormone-refractory metastatic prostate cancer.

DRUG REGIMEN Day 1 PREMEDICATION: DEXAMETHASONE

DOCETAXEL 30mg/m2

in 250ml sodium chloride 0.9% infusion over 1 hour Day 8 PREMEDICATION: DEXAMETHASONE

DOCETAXEL 30mg/m2


DOCETAXEL 30mg/m2


DOCETAXEL 30mg/m2


DOCETAXEL 30mg/m2

in 250ml sodium chloride 0.9% infusion over 1 hour

Cycle Frequency: Every 42 days for 2 cycles

DOSE MODIFICATIONS Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Hepatic impairment: Patients who have both elevations of transaminases (ALT and/or AST) > 1.5 x ULN and ALP > 2.5 x ULN: Give 75% dose. Patients with serum bilirubin > ULN and/or ALT and AST > 3.5 x ULN associated with ALP > 6 x ULN: docetaxel should not be used unless strictly indicated.


Give Discuss

Hb x g/dL ≥10 < 10


2) Non urgent tests. Tests relating to disease response/progression

CONCURRENT MEDICATION Prednisolone 5mg bd po continuously.

Docetaxel weekly

Urology TSSG Chair Authorisation: Date:


Version 3.2



ANTIEMETIC POLICY Low emetogenic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Ensure pre-medication is given Dermatology – hand-foot syndrome REFERENCES 1. Tax 327 trial. NEJM, 2004, Vol 351, No. 15, 1502-1512. 2. Hainsworth et al. Weekly Docetaxel/estramustine for prostate cancer: a phase II trial. Clin

Genitourin Cancer, 2006, 4 (4): 287-92. 3. Joshua et al. Weekly Docetaxel as second-line treatment after Mitoxantrone for androgen

independent prostate cancer. Intern Med J. 2005, 35 (8): 468-72. 4. Bertelli et al. Weekly Docetaxel and zoledronic acid every four weeks in hormone refractory

prostate cancer. Cancer Chemother Pharmacol. 2006, 57 (1) 46-51. 5. Di Lorenzo et al, Weekly docetaxel and vinorelbine as first line treatment in patients with

hormone refractory prostate cancer. Eur Urol, 2004, 46 (6): 712-716. 6. Ferrero et al. A weekly schedule for docetaxel for metastatic hormone refractory prostate

cancer. Oncology, 2004, 66 (4): 281-7. 7. Beer et al. Weekly docetaxel in elderly patients with prostate cancer. Clin Prostate Cancer,

2003, 2 (3): 167-72. 8. Gravis et al. Weekly Docetaxel for symptomatic metastatic hormone refractory prostate cancer.

Cancer 2003, 98 (8), 1627-34. 9. Petrioli et al. Weekly low dose docetaxel in advanced hormone resistant prostate cancer

patients previously exposed to chemotherapy. 2003, Oncology, 64 (4): 300-305. 10. Beer et al, Weekly high dose calcitriol and docetaxel in metastatic androgen independent

prostate cancer. 2003, 21 (1): 123-8. 11. Beer et al. Phase II study of weekly docetaxel in symptomatic androgen-independent

prostate cancer. Ann Oncol, 2001, 12 (9): 1273-9.

Docetaxel weekly



Version 3.2



CMV (Bladder) Indications Metastatic bladder cancer and adjuvant bladder cancer

DRUG REGIMEN Day 1 Pre-hydration regimen

METHOTREXATE 30mg/m2

IV bolus VINBLASTINE 4mg/m2

(Max. 10mg) in 50ml sodium chloride 0.9% IV infusion over 10 minutes CISPLATIN 100mg/m2

in 1000ml sodium chloride infusion over 2 hours Post-hydration regimen Day 8 METHOTREXATE 30mg/m2


(Max. 10mg) in 20ml sodium chloride 0.9% IV over 10 minutes

Cycle Frequency: Every 21 days maximum 6 cycles

DOSE MODIFICATIONS Cisplatin: GFR > 60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss with Consultant or Registrar before administration Methotrexate: GFR 60ml/min give 65% dose GFR 45ml/min give 50% dose GFR <30 ml/min omit Bilirubin 51-85micromol/L or AST>180 give 75% dose Bilirubin >85micromol/L omit Vinblastine: Bilirubin 26-51 micromol/L or AST/ALT>60-80 give 50% dose Bilirubin >51 micromol/L and AST/ALT normal give 50% dose Bilirubin >51 micromol/L and AST/ALT >180 omit

CMV Urology TSSG Chair Authorisation: Date:


Version 3.2




Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) 2) Non-urgent tests Tests relating to disease response/progression

CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV For patient requiring Folinic acid support the dose is Folinic acid 15mg PO/IV every 6 hours for 6 doses starting 24 hours after Methotrexate especially if: . ● Pleural effusions/ascites . ● Previous mucositis . ● Serum creatinine > 120micromols/L

ANTI-EMETIC POLICY Highly emetogenic day 1 Minimal emetogenic risk day 8

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Methotrexate induced mucositis - folinic acid (calcium folinate) rescue (see concurrent medication) Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Caution with furosemide. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


CMV Urology TSSG Chair Authorisation: Date:


Version 3.2



CISPLATIN / GEMCITABINE (Bladder) Indications: Metastatic bladder cancer and neoadjuvant or adjuvant bladder cancer

DRUG REGIMEN Day 1 Pre-hydration regimen GEMCITABINE 1000mg/ m2 in 250ml sodium chloride 0.9% infusion over 30 minutes CISPLATIN 70mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours Post-hydration regimen Day 8 GEMCITABINE 1000mg/ m2 in 250ml sodium chloride 0.9% infusion over 30 minutes

Cycle Frequency: Every 21 days (6 cycles for metastatic disease, 4 cycles for adjuvant)

DOSE MODIFICATIONS Cisplatin: GFR > 60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration Gemcitabine: CrCl <30ml/min consider dose reduction (Clinical decision)

Neutrophils >1.0x109/L and platelets >100x109/L give 100% dose Neutrophils 0.5-1.0x109/L or platelets 50-100x109/L give 75% dose or delay based on clinical assessment Neutrophils <0.5x109/L or platelets <50x109/L delay treatment Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose Omit if treatment is delayed for more than 4 weeks but continue with Cisplatin

Gemcitabine / cisplatin



Version 3.2




Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion. (Cisplatin) 2) Non-urgent tests Tests relating to disease response/progression

CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV

ANTI-EMETIC POLICY Highly emetogenic day 1 Low emetogenic risk days 8, 15

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Diarrhoea – see dose modifications Mucositis – see dose modifications Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Gemcitabine / cisplatin



Version 3.2



GEMCITABINE / CARBOPLATIN (Bladder) Indications: Metastatic bladder cancer when cisplatin is contra-indicated or unsuitable

DRUG REGIMEN Day 1 GEMCITABINE 1000mg/m2

in 250ml sodium chloride 0.9% infusion over 30 minutes CARBOPLATIN (AUC= 4.5) in 500ml glucose 5% infusion over 1 hour Dose = (25 + GFR) x AUC

Day 8 GEMCITABINE 1000mg/m2

in 250ml sodium chloride 0.9% infusion over 30 minutes

Cycle Frequency: Every 21 days for 6 cycles NB Ideally GFR should be measured using EDTA If not it may be calculated

DOSE MODIFICATIONS Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/L Contraindicated if CrCl<20ml/min Gemcitabine: If CrCl <30ml/min consider dose reduction (Clinical decision)

Neutrophils >1.0x109/L and platelets >100x109/L give 100% dose Neutrophils 0.5-1.0x109/L or platelets 50-100x109/L give 75% dose or delay based on clinical assessment Neutrophils <0.5x109/L or platelets <50x109/L delay treatment Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose Omit if treatment is delayed for more than 4 weeks but continue with Cisplatin

Gemcitabine / carbo



Version 3.2




Give Discuss

Hb x g/dL ≥10 < 10


Liver function tests (LFT)

Creatinine clearance (GFR) ideally measured by 51Cr-EDTA or calculated at the Consultants discretion (Carboplatin). 2) Non-urgent tests Tests relating to disease response/progression

CONCURRENT MEDICATION Carboplatin- Anaphylaxis treatment should be prescribed if the patient has had an anaphylactic episode previously. DEXAMETHASONE 20mg IV bolus CHLORPHENAMINE 10mg IV bolus RANITIDINE 50mg IV bolus Carboplatin should be given at a slower rate e.g. 2-4 hours.

ANTI-EMETIC POLICY Moderately emetogenic day 1 Low emetic risk day 8

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Diarrhoea – see dose modifications Mucositis – see dose modifications REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Gemcitabine / carbo



Version 3.2



MVAC (Bladder) Indications: Metastatic bladder cancer and adjuvant bladder cancer




in 50ml sodium chloride 0.9% IV infusion over 10 minutes DOXORUBICIN 30mg/m2

IV bolus CISPLATIN 70mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours Post-hydration regimen Day 15 METHOTREXATE 30mg/m2


in 50ml sodium chloride 0.9% IV infusion over 10 minutes Day 22 METHOTREXATE 30mg/m2


in 50ml sodium chloride 0.9% IV infusion over 10 minutes

Cycle Frequency: Every 28 days (6 cycles for metastatic disease, 4 cycles for adjuvant)

DOSE MODIFICATIONS Doxorubicin: Dose reduce in severe renal impairment. Bilirubin 20-50micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit If ALT/AST is 2-3 x ULN give 75% dose If ALT/AST is >3 x ULN give 50% dose Maximum cumulative dose = 450-550 mg/m2

(in normal cardiac function) = 400 mg/m2

(in patients with cardiac dysfunction or exposed to mediastinal irradiation)

Cisplatin: GFR > 60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss with Consultant or Registrar before administration Vinblastine: Bilirubin 26-51 micromol/L or AST/ALT>60-80 give 50% dose Bilirubin >51 micromol/L and AST/ALT normal give 50% dose Bilirubin >51 micromol/L and AST/ALT >180 omit

MVAC Urology TSSG Chair Authorisation: Date:


Version 3.2



Methotrexate: GFR 60ml/min give 65% dose GFR 45ml/min give 50% dose GFR < 30 ml/min omit Bilirubin 51-85micromol/L or AST>180 give 75% dose Bilirubin >85micromol/L omit


Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) 2) Non-urgent tests; tests relating to disease response/progression

CONCURRENT MEDICATION For patient requiring Folinic acid support the dose is Folinic acid 15mg PO/IV every 6 hours for 6 doses starting 24 hours after Methotrexate especially if: . ● Pleural effusions/ascites . ● Previous mucositis . ● Serum creatinine >120 micromols/L

Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV

ANTI-EMETIC POLICY Highly emetogenic day 1 Minimal emetogenic risk days 15, 22

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Methotrexate induced mucositis - folinic acid (calcium folinate) rescue (see concurrent medication) Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. Cardiotoxicity – monitor cardiac function



MVAC Urology TSSG Chair Authorisation: Date:


Version 3.2



MVAC ACCELERATED (Bladder) Indications: Neoadjuvant bladder cancer pre surgery and metastatic bladder cancer




in 50ml sodium chloride 0.9% IV infusion over 10 minutes DOXORUBICIN 30mg/m2

IV bolus CISPLATIN 70mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours Post-hydration regimen Days 4 to 10 GCSF as per local policy

Cycle Frequency: Every 14 days for 3 cycles pre-surgery neoadjuvant, 6 cycles for metastatic disease

DOSE MODIFICATIONS Doxorubicin: Dose reduce in severe renal impairment. Bilirubin 20-50micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit If ALT/AST is 2-3 x ULN give 75% dose If ALT/AST is >3 x ULN give 50% dose Maximum cumulative dose = 450-550 mg/m2

(in normal cardiac function) = 400 mg/m2

(in patients with cardiac dysfunction or exposed to mediastinal irradiation)

Cisplatin: GFR > 60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss with Consultant or Registrar before administration Vinblastine: Bilirubin 26-51 micromol/L or AST/ALT>60-80 give 50% dose Bilirubin >51 micromol/L and AST/ALT normal give 50% dose Bilirubin >51 micromol/L and AST/ALT >180 omit

MVAC accelerated



Version 3.2



Methotrexate: GFR 60ml/min give 65% dose GFR 45ml/min give 50% dose GFR < 30 ml/min omit Bilirubin 51-85micromol/L or AST>180 give 75% dose Bilirubin >85micromol/L omit


Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5

Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) 2) Non-urgent tests; tests relating to disease response/progression

CONCURRENT MEDICATION For patient requiring Folinic acid support the dose is Folinic acid 15mg PO/IV every 6 hours for 6 doses starting 24 hours after Methotrexate especially if: . ● Pleural effusions/ascites . ● Previous mucositis . ● Serum creatinine >120 micromols/L

Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV

ANTI-EMETIC POLICY Highly emetogenic day 1

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Methotrexate induced mucositis - folinic acid (calcium folinate) rescue (see concurrent medication) Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. Cardiotoxicity – monitor cardiac function



MVAC accelerated



Version 3.2



BEP (3 day) adjuvant (NSGCT) Indications: Adjuvant treatment for non-metastatic non-seminomatous germ cell tumour (stage 1 only) in patients with vascular or lymphatic invasion (risk of relapse up to 40% without treatment). Consider for patients who are unable to attend for intensive outpatient surveillance.


ETOPOSIDE 120mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours CISPLATIN 50mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours Post-hydration regimen Day 2 Pre-hydration regimen

ETOPOSIDE 120mg/m2


in 1000ml sodium chloride 0.9% infusion over 2 hours BLEOMYCIN 30,000units in 3ml Lidocaine 1% IM injection (daypatient) or in 1000ml sodium chloride 0.9% IV infusion over 12 hours (inpatient)

Post-hydration regimen Day 3 ETOPOSIDE 120mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours Day 9 HYDROCORTISONE 100mg IM

BLEOMYCIN 30,000units in 3ml 1% lidocaine IM Day 16 HYDROCORTISONE 100mg IM

BLEOMYCIN 30,000units in 3ml 1% lidocaine IM Cycle Frequency: Every 21 days for TWO cycles ONLY

DOSE MODIFICATIONS Any delays with/without dose modification may cause treatment failure. Discuss with Consultant before delaying treatment or reducing doses of any drug

Cisplatin: GFR > 60ml/min give 100% dose GFR 45 - 59 mL/min give 75% dose (to be discussed with consultant, consider full dose) GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss Consultant before administration

Bleomycin: GFR > 50ml/min give 100% dose GFR 10-50ml/min give 75% dose GFR <10ml/min give 50% dose

BEP 3 day adjuvant



Version 3.2



Etoposide: CrCl > 50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L 50% give dose Bilirubin >51micromol/L or AST >180u/L Clinical decision

INVESTIGATIONS Check patient has had sperm-banking prior to starting first treatment Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin)

2) Non-urgent tests relating to disease response/progression

CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 200ml Mannitol 10% IV or consider 20 - 40mg Furosemide PO/IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 200ml Mannitol 10% IV or consider 20 ¬ 40 mg Furosemide PO/IV

ANTI-EMETIC POLICY Highly emetogenic. days 1, 2 Low emetogenic risk day 3 Minimal emetogenic risk days 8, 15

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Pulmonary function tests (including transfer factor) prior to commencement of BEP. If breathlessness or infiltrates appear not attributable to tumour or co-existence of lung disease bleomycin must be stopped immediately. Consider treatment with corticosteroids and a broad spectrum antibiotic and / referral to chest team. Investigation of choice high resolution CT chest. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.



BEP 3 day adjuvant



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BEP (3 day) metastatic (NSGCT) Indications: Good prognosis metastatic non-seminomatous germ cell tumour (3 cycles only)


ETOPOSIDE 166mg/m2



ETOPOSIDE 166mg/m2




in 1000ml sodium chloride 0.9% infusion over 2 hours Day 9 HYDROCORTISONE 100mg IM

BLEOMYCIN 30,000units in 3ml 1% lidocaine IM Day 16 HYDROCORTISONE 100mg IM

BLEOMYCIN 30,000units in 3ml1% lidocaine IM

NB Day 9 may be given on day 8 instead. Day 16 may be given on day 15 instead (RBH). NB Day 9 and 16 are given as outpatient treatments Cycle Frequency: Every 21 days for THREE cycles ONLY can give 4 cycles (good prognosis metastatic germ cell tumour, 4th cycle excluding bleomycin)

DOSE MODIFICATIONS Any delays with/without dose modification may cause treatment failure. Discuss with Consultant before delaying treatment or reducing doses of any drug.

Cisplatin: GFR > 60ml/min give 100% dose GFR 45 - 59 mL/min give 75% dose (to be discussed with consultant, consider full dose) GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss with Consultant before administration

Bleomycin: GFR > 50ml/min give 100% dose GFR 10-50ml/min give 75% dose GFR <10ml/min give 50% dose

BEP 3 day metastatic



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Etoposide: CrCl > 50 ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl<15 ml/min give 50% dose Confirm with Consultant Bilirubin 26-51 micromol/L or ALT/AST 60-180 u/L give 50% dose Bilirubin >51 micromol/L or ALT/AST >180 u/L Clinical decision

INVESTIGATIONS Check patient has had sperm banking prior to first treatment. Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 EDTA or Creatinine clearance (GFR) calculated at the Consultants discretion (Cisplatin)

2) Non-urgent tests Tests relating to disease response/progression

CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 200ml Mannitol 10% IV or consider 20 - 40mg Furosemide PO/IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 200ml Mannitol 10% IV or consider 20 - 40mg Furosemide PO/IV

ANTI-EMETIC POLICY Highly emetogenic days 1, 2 Low emetogenic risk day 3 Minimal emetogenic risk days 9, 16

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Pulmonary function tests (including transfer factor) prior to commencement of BEP. If breathlessness or infiltrates appear not attributable to tumour or co-existence of lung disease bleomycin must be stopped immediately. Consider treatment with corticosteroids and a broad spectrum antibiotic and / referral to chest team. Investigation of choice high resolution CT chest. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.



BEP 3 day metastatic



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BEP (5 day) metastatic (NSGCT) Indication: Intermediate or poor prognosis non-seminomatous germ cell tumour


ETOPOSIDE 100mg/m2



ETOPOSIDE 100mg/m2



Post-hydration regimen Day 3 Pre-hydration regimen

ETOPOSIDE 100mg/m2



ETOPOSIDE 100mg/m2



ETOPOSIDE 100mg/m2

in 1000ml sodium chloride infusion over 2 hours CISPLATIN 20mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours Post-hydration regimen Day 9 HYDROCORTISONE 100mg in 2ml water for injection IM

BLEOMYCIN 30,000 units in 3ml Lidocaine 1% IM Day 16 HYDROCORTISONE 100mg in 2ml water for injection IM

BLEOMYCIN 30,000 units in 3ml Lidocaine 1% IM

NB Day 9 may be given on day 8 instead. Day 16 may be given on day 15 instead (RBFT) NB Day 9 and 16 are given as daypatient treatments

Cycle Frequency: Every 21 days for FOUR cycles ONLY

BEP 5 day Urology TSSG Chair Authorisation: Date:


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DOSE MODIFICATIONS Any delays with/without dose modification may cause treatment failure. Discuss with Consultant before delaying treatment or reducing doses of any drug Cisplatin: GFR > 60ml/min give 100% dose GFR 45 - 59 mL/min give 75% dose (to be discussed with consultant, consider full dose) GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss. Bleomycin: GFR > 50ml/min give 100% dose GFR 10-50 ml/min give 75% dose GFR < 10 ml/min give 50% dose Confirm with SpR or Consultant If patient is breathless discuss with Consultant Etoposide: CrCl > 50 ml/min give 100% dose CrCl 15-50 ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51 micromol/L or ALT/AST 60-180 u/L give 50% dose Bilirubin >51 micromol/L or ALT/AST >180 u/L omit dose

INVESTIGATIONS Check patient has had sperm-banking prior to first cycle of chemotherapy Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss

Hb x g/dL ≥10 < 10


Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) 2) Non-urgent tests Tests relating to disease response/progression



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CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV Consider GCSF for next cycle if patient experiences an episode of neutropenic sepsis

ANTI-EMETIC POLICY Highly emetogenic days 1, 2, 3, 4, 5 Minimal emetogenic risk days 9, 16

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Pulmonary function tests (including transfer factor) prior to commencement of BEP. If breathlessness or infiltrates appear not attributable to tumour or co-existence of lung disease bleomycin must be stopped immediately. Consider treatment with corticosteroids and a broad spectrum antibiotic and / referral to chest team. Investigation of choice high resolution CT chest. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic




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CARBOPLATIN (Seminoma) Indication: Seminoma stage 1 (adjuvant single dose)

DRUG REGIMEN Day 1 CARBOPLATIN (AUC = 7) in 500ml glucose 5% infusion over 60 minutes

Dose = (25 + GFR) x AUC

Cycle Frequency: ONCE only

DOSE MODIFICATIONS Discuss if patient has a serum creatinine > 150 micromol/L Contraindicated if CrCl<20ml/min


Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) ideally measured by 51Cr-EDTA (or calculated) at the Consultants discretion (Carboplatin).


CONCURRENT MEDICATION Anaphylaxis treatment should be prescribed if the patient has had an anaphylactic episode previously. DEXAMETHASONE 20mg IV bolus CHLORPHENAMINE 10mg IV bolus RANITIDINE 50mg IV bolus Carboplatin should be given at a slower rate e.g. 2-4 hours.

ANTI-EMETIC POLICY Moderately emetogenic

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS



Carboplatin seminoma



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PACLITAXEL / IFOSFAMIDE / CISPLATIN (TIP) Indications: Salvage for metastatic germ cell

DRUG REGIMEN Days 1 PRE-MEDICATION 30 mins prior to infusion: DEXAMETHASONE 20mg IV bolus RANITIDINE 50mg IV bolus CHLORPHENAMINE 10mg IV bolus

PACLITAXEL 175mg/m2

in 500ml sodium chloride 0.9% infusion over 3 hours (PVC free) Days 1 to 5 MESNA 200mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes

IFOSFAMIDE 1g/m2 with MESNA 1g/m2 in 1L sodium chloride 0.9% infusion over 1 hour MESNA 600mg/m2 in 500ml sodium chloride 0.9% over 12 hours Pre-hydration CISPLATIN 20mg/m2 IV in 1000ml sodium chloride 0.9% infusion over 2 hours Post hydration

Cycle Frequency: Every 21 days for 4 to 6 cycles

DOSE MODIFICATIONS If patient complains of tinnitus, tingling of fingers and/or toes or motor weakness or has/had previous neutropenic sepsis, discuss with Consultant or Registrar before administration.

Cisplatin: GFR > 60ml/min give 100% dose GFR 45 - 59 mL/min give 75% dose GFR < 45ml/min consider carboplatin Ifosfamide: GFR >60ml/min give 100% dose GFR 40-59ml/min give 70% dose GFR <40ml/min clinical decision. Creatinine >120micromol/L ifosfamide not recommended Discuss if *Bilirubin >17 micromol/L *AST and Alk Phos > 2.5 x upper limit of normal Paclitaxel: Bilirubin <1.25xULN and AST <10xULN dose at 175mg/m2 Bilirubin <26micromol/L give 135mg/m2 Bilirubin 27-51micromol/L give 75mg/m2 Bilirubin >51micromol/L give 50mg/m2

TIP Urology TSSG Chair Authorisation: Date:


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Give Discuss

Hb x g/dL ≥9 < 9

Plt x 109/L ≥100 < 100 WBC x 109/L ≥3.0 < 3.0

Bilirubin ≥25 <25 Creatinine clearance (GFR) ideally measured by 51Cr-EDTA or calculated at the Consultants discretion Neurological assessment and neurological toxicity 2) Non urgent tests. Tests relating to disease response/progression

CONCURRENT MEDICATION Ensure Pre medication given with paclitaxel Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is <100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV

ANTIEMETIC POLICY High emetic risk all days

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cisplatin Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.

Paclitaxel- (2% risk of severe hypersensitivity) Reactions range from mild hypotension (lightheadedness) to full cardiac collapse (anaphylactic shock). Discontinue infusion and resuscitate appropriate to reaction. If reaction is mild and settles promptly (i.e. within 5 10mins), cautiously restart at a slower rate under close supervision. If further reactions occur stop treatment. Ensure pre-medication is given.

Ifosfamide encephalopathy - methylene blue and supportive therapy Methylthioninium chloride (methylene blue) Methylthioninium chloride (methylene blue) can be given as prophylaxis against, or treatment of, ifosfamide-induced encephalopathy (See specific neural toxicity grade and nomogram below). This should be started on the day of ifosfamide administration and continued for 24 hours after administration or until neurotoxic symptoms subside. Other risk factors include cisplatin, brain irradiation, hepatic failure and advancing age. Dose: 50mg tds IV or orally. (NB. 50mg = 5ml of 1% solution.)



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Administration IV: administer 50mg in 50 to 100ml sodium chloride 0.9% or glucose 5%, over 15 to 30 minutes Orally: use injection for oral administration. Dilute one ampoule in 100ml water before taking orally to minimise GI effects. Drink through a straw to avoid staining teeth. 53-97% oral absorption Nephrotoxicity-Irreversible renal failure and tubular damage can occur, and this is more frequent with cumulative doses over 25 – 50g/m2

of Ifosfamide. Dose reductions should be instituted for GFR and changes in fractional phosphate clearance (Tmp/GFR mmol/l). Neural toxicity grade Classify toxicity as grade 0-1, 2 or 3-4 and adjust ifosfamide treatment as indicated if either GFR or Tp/Ccrea (Tmp/GFR) or HCO3 is reduced.

Toxicity Grade* GFR (ml/min/1.73m2)

Tp/Ccrea (Tmp/GFR) (mmol/l)

HCO3** (mmol/l)

Action (apply worst grade)

Grade 0/1 ≥60 ≥1.00 ≥17.0 Ifos dose 100%

Grade 2 40-59 0.8-0.99 14.0-16.9 Ifos dose 70% of total

Grade 3/4 ≤40 ≤0.8 ≤14.0 ***Switch to Cyclophosphamide

*Toxicity is scored from 0-4, analogous to the CTC system, but for the purpose of modifying treatment grades 0-1 and 3-4 are considered together. ** Low values of HCO3 should be re-checked when the patient is clinically stable (to rule out infection as a cause, etc) before modifying treatment ***Discuss with consultant before and to confirm substitution of ifosfamide with cyclophosphamide 1500mg/m2/day Fractional phosphate clearance calculated as below Tp/Ccrea = Phosphateserum – Phosphateurine x creatinineserum Creatinineurine [mmol/ml]



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Neural toxicity nomogram

REFERENCES 1. ASWCS Chemotherapy handbook Jan 2005 2. Mead G et al on behalf of the MRC Testicular tumour working party. A phase 2 trial of TIP given

as second line (post BEP) 3. Salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council

trial. British Journal of Cancer (2005) 93, 178-184 4. Motzer RJ et al Paclitaxel, ifosfamide and cisplatin second line therapy for patients with

relapsed testicular germ cell cancer. J Clin Oncol 18: 2413-2418



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POMB / ACE (Germ cell) Indication: Metastatic germ cell

DRUG REGIMEN POMB Day 1 VINCRISTINE 1mg/m2 (max 2mg) IV infusion in 50ml sodium chloride 0.9% METHOTREXATE 300mg/m2 in 1000ml sodium chloride 0.9% over 12 hours 1000ml sodium chloride 0.9% + 20mmol KCl over 4 hours Day 2 BLEOMYCIN 30,000iu in 2000ml sodium chloride 0.9% infusion over 24 hours FOLINIC ACID 15mg qds PO for 6 doses starting 24 hours after methotrexate Day 3 Pre-hydration regimen CISPLATIN 60mg/m2 in 500ml sodium chloride 0.9% infusion over 4 hours CISPLATIN 60mg/m2 in 500ml sodium chloride 0.9% infusion over 4 hours Post-hydration regimen

Cycle Frequency: Every 14 days alternating with ACE (see regimen sequence below) ACE Day 1 DACTINOMYCIN 500micrograms IV bolus ETOPOSIDE 100mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours Day 2 DACTINOMYCIN 500micrograms IV bolus ETOPOSIDE 100mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours Day 3 CYCLOPHOSPHAMIDE 500mg/m2 IV bolus DACTINOMYCIN 500micrograms IV bolus ETOPOSIDE 100mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours Cycle frequency: Every 14 days alternating with POMB (see regimen sequence below) Regimen sequence: POMB POMB ACE POMB ACE POMB ACE

POMB-ACE Urology TSSG Chair Authorisation: Date:


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DOSE MODIFICATIONS POMB Bleomycin: GFR >50ml/min give 100% dose GFR 10-50 ml/min give 75% dose GFR < 10 ml/min give 50% dose Vincristine: Bilirubin 25-51 or AST 60-180u/Lgive 50% dose Bilirubin >51 micromol/L and normal AST give 50% dose Bilirubin >51micromol/L and AST >180u/L omit Methotrexate: CrCl 60 mL/min give 65% dose CrCl 45 mL/min give 50% dose CrCl < 30 mL/min omit dose Bilirubin 51 - 85 micromol/L or AST >180 u/L give 75% dose Bilirubin >85micromol/L omit Cisplatin: GFR > 60ml/min give 100% dose

GFR 45 - 59 mL/min give 75% dose GFR < 45ml/min consider carboplatin

ACE Etoposide: CrCl > 50ml/min give 100% dose CrCl 15-50 ml/min give 75% dose CrCl < 15 ml/min give 50% dose Bilirubin 26-51 micromol/L or AST 60-180 u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Cyclophosphamide: GFR >20ml/min give 100% dose GFR 10 - 20 mL/min give 75% dose GFR < 10 mL/min give 50% dose Dactinomycin: Consider dose reduction in severe hepatic disease.



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Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) ideally measured by 51Cr-EDTA or calculated at the Consultants discretion. 2) Non-urgent tests Tests relating to disease response/progression

CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per inpatient schedule at the end of the TVCN protocols. If fluid balance is > 2L positive after 8 hours post hydration OR if patient gains >2kg in weight or urine output <100ml//hour during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV

ANTI-EMETIC POLICY Moderately emetogenic for POMB day 1 Minimal emetogenic for POMB day 2 Highly emetogenic for POMB day 3 Moderately emetogenic risk for ACE

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Pulmonary function tests (including transfer factor) prior to each cycle of BEP. If breathlessness or infiltrates appear not attributable to tumour or co-existence of lung disease bleomycin must be stopped immediately. Treat patients with corticosteroids and a broad spectrum antibiotic. Cyclophosphamide may irritate bladder, drink copious volumes of water. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. Methotrexate induced mucositis - folinic acid (calcium folinate) rescue (see drug regimen). REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic




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PEC (Germ cell)

Indication: relapsed germ cell tumour

DRUG REGIMEN Day 1 PRE-MEDICATION 30 mins prior to infusion: DEXAMETHASONE 20mg IV bolus RANITIDINE 50mg IV bolus CHLORPHENAMINE 10mg IV bolus

PACLITAXEL 90mg/m2

in 500ml sodium chloride 0.9% infusion over 3 hours ETOPOSIDE 150mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours Day 15 PRE-MEDICATION 30 mins prior to infusion: DEXAMETHASONE 20mg IV bolus RANITIDINE 50mg IV bolus CHLORPHENAMINE 10mg IV bolus

PACLITAXEL 90mg/m2

in 500ml sodium chloride 0.9% infusion over 3 hours Pre-hydration regimen CISPLATIN 60mg/m2 in 1000ml sodium chloride 0.9% infusion over 4 hours Post-hydration regimen

Cycle Frequency: Every 28 days for 6 cycles

DOSE MODIFICATIONS If patient complains of tinnitus, tingling of fingers and/or toes or motor weakness discuss with Consultant or Registrar before administration.

Paclitaxel: Bilirubin <1.25xULN and AST <10xULN dose at 100% Bilirubin >17micromol/L dose reduction required AST and Alk phos > 3x normal dose reduction required

Cisplatin: GFR > 60ml/min give 100% dose GFR 45 - 59 mL/min give 75% dose GFR < 40ml/min consider carboplatin

Etoposide: CrCl > 50ml/min give 100% dose CrCl 15-50 mL/min give 75% dose CrCl <15mL/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision

PEC Urology TSSG Chair Authorisation: Date:


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Give Discuss

Hb x g/dL ≥10 < 10


Liver function tests (LFT)

Creatinine clearance (GFR) ideally measured by 51Cr-EDTA or calculated at the Consultants discretion 2) Non urgent tests Tests relating to disease response/progression

CONCURRENT MEDICATION Ensure pre medication given Ensure adequate pre-and post-hydration prescribed as per inpatient schedule at the end of the TVCN protocols. If fluid balance is > 2L positive after 8 hours post hydration, or weight gain of >2kg, OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV

ANTIEMETIC POLICY Moderately emetogenic day 1 Highly emetogenic day 15

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Paclitaxel (2% risk of severe hypersensitivity) Reactions range from mild hypotension (light-headedness) to full cardiac collapse (anaphylactic shock). Discontinue infusion and resuscitate appropriate to reaction. If reaction is mild and settles promptly (i.e. within 5-10 minutes), cautiously restart at a slower rate under close supervision. If further reactions occur stop treatment. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


PEC Urology TSSG Chair Authorisation: Date:


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EP (Seminoma) Indication: First line for metastatic seminoma


ETOPOSIDE 166mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours

CISPLATIN 50mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours (daypatient) or 4 hours (inpatient) Post-hydration regimen

Day 2 Pre-hydration regimen ETOPOSIDE 166mg/m2


in 1000ml sodium chloride 0.9% infusion over 2 hours Post-hydration regimen Day 3 ETOPOSIDE 166mg/m2

in 1000ml sodium chloride 0.9% infusion over 2 hours

Cycle Frequency: Every 21 Days for FOUR cycles ONLY

DOSE MODIFICATIONS Any delays with/without dose modification may cause treatment failure. Discuss with Consultant before delaying treatment or reducing doses of any drug if patient has had neutropenic sepsis. Cisplatin: GFR > 60ml/min give 100% dose GFR 45 - 59 ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss with Consultant before administration Etoposide: CrCl > 50ml/min give 100% dose GFR 15 - 50 ml/min give 75% dose GFR < 15 ml/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L clinical decision

EP seminoma



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INVESTIGATIONS Check patient has had sperm-banking prior to starting first treatment Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss

Hb x g/dL ≥10 < 10


Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) 2) Non-urgent tests Tests relating to disease response/progression


ANTI-EMETIC POLICY Highly emetogenic. days 1, 2 Low emetic risk day 3

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


EP seminoma



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BEP (3 day) (Unknown primary adenocarcinoma) Indications: Adenocarcinoma of unknown primary


ETOPOSIDE 166mg/m2



ETOPOSIDE 166mg/m2


in 1000ml sodium chloride 0.9% infusion over 2 hours (daypatient) or 4 hours (inpatient) BLEOMYCIN 30,000units in 3ml Lidocaine 1% IM injection (daypatient) or in 1000ml sodium chloride 0.9% IV infusion over 12 hours (inpatient)


in 1000ml sodium chloride 0.9% infusion over 2 hours Cycle Frequency: Every 21 days for up to 6 cycles

DOSE MODIFICATIONS Any delays with/without dose modification may cause treatment failure. Discuss with Consultant before delaying treatment or reducing doses of any drug. Cisplatin: GFR > 60ml/min give 100% dose GFR 45 - 59 mL/min give 75% dose (to be discussed with consultant, consider full dose) GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes discuss with Consultant before administration Bleomycin: CrCl > 50ml/min give 100% dose CrCl 10-50 ml/min give 75% dose CrCl < 10 ml/min give 50% dose

BEP adeno Urology TSSG Chair Authorisation: Date:


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Etoposide: CrCl > 50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or ALT/AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L clinical decision

INVESTIGATIONS Check patient has had sperm banking prior to first treatment. Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated using or EDTA at the Consultants discretion (Cisplatin)

2) Non-urgent tests- Tests relating to disease response/progression


ANTI-EMETIC POLICY Highly emetogenic days 1, 2 Low emetogenic risk day 3

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Pulmonary function tests (including transfer factor) prior to each cycle of BEP. If breathlessness or infiltrates appear not attributable to tumour or co-existence of lung disease bleomycin must be stopped immediately. Treat patients with corticosteroids and a broad spectrum antibiotic. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.



BEP adeno Urology TSSG Chair Authorisation: Date:


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AXITINIB (Renal cell carcinoma) Indication: Treatment of advanced and renal cell carcinoma after failure of prior treatment with Sunitinib or a cytokine. Funding for this should be obtained for each individual patient.

DRUG REGIMEN Day 1 Axitinib 5mg orally twice daily Patients who tolerate the axitinib starting dose of 5mg twice daily with no adverse reactions > Grade 2 for two consecutive weeks may have their dose increased to 7mg twice daily unless the patient’s blood pressure is > 150/90 mmHg or the patient is receiving antihypertensive treatment. Subsequently, using the same criteria, patients who tolerate an axitinib dose of 7mg twice daily may have their dose increased to a maximum of 10mg twice daily. Cycle Frequency: Continuous (28 day cycles)

DOSE MODIFICATIONS Axitinib: Any dose modifications should be discussed with a Consultant.

Management of some adverse reactions may require temporary or permanent discontinuation and/or dose reduction of axitinib therapy. When dose reduction is necessary, the axitinib dose may be reduced to 3mg twice daily and further to 2mg twice daily.

Hepatic impairment A dose decrease is recommended when administering axitinib to patients with moderate hepatic impairment (Child-Pugh class B). Axitinib has not been studied in patients with severe hepatic impairment (Child-Pugh class C) and should not be used in this population.

Axitinib Urology TSSG Chair Authorisation: Date:


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Give Discuss

Hb x g/dL ≥10 < 10


Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) Thyroid function tests Ask GP to monitor blood pressure on a regular basis, weekly initially. 2) Non urgent blood tests Tests relating to disease response/progression


ANTIEMETIC POLICY

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Skin - skin discolouration and depigmentation of the hair and skin may occur. Haemorrhage – an increased risk of bleeding may occur. Hypertension – treatment induced hypertension. Axitinib dose should be reduced if persistent hypertension despite use of anti-hypertensives. Gastrointestinal –gastrointestinal complications including gastrointestinal perforation or fistula should be monitored for throughout treatment. Hypothyroidism / hyperthyroidism REFERENCES 1. SPC September 2012

Axitinib Urology TSSG Chair Authorisation: Date:


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EVEROLIMUS (Renal cell carcinoma) Indication: Treatment of advanced renal cell carcinoma. Ensure funding is available for patient prior to prescribing.

DRUG REGIMEN Day 1 Everolimus 10mg orally daily Cycle Frequency: Daily for 4 weeks continuously until progression

DOSE MODIFICATIONS Pazopanib: Any dose modifications should be discussed with a Consultant.

Renal impairment No dose adjustment is required in patients with renal impairment.

Hepatic impairment For patients with moderate hepatic impairment (Child-Pugh class B), the dose should be reduced to 5 mg daily. Everolimus has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C) and is not recommended for use in this patient population.


Give Discuss

Hb x g/dL ≥10 < 10

Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Routine bloods: FBC, renal function, liver function. Random blood sugar, lipid profile; if elevated to repeat on fasting blood Baseline imaging: CT and/or MRI at baseline and every three months. 2) Non urgent tests Tests relating to disease response/progression



Everolimus Urology TSSG Chair Authorisation: Date:


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ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Increased glucose, lipids and triglycerides Decreased haemoglobin, lymphocytes, neutrophils and platelets Hypersensitivity reactions Pneumonitis, Infections Oral ulceration REFERENCES 1. SPC May 2010 2. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22.

Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group.

3. Cancer. 2010 Jun 14. [Epub ahead of print] Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors.Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; for the RECORD‐1 Study Group.

4. Med Oncol. 2010 Aug 10. [Epub ahead of print] Long-term response with everolimus for metastatic renal cell carcinoma refractory to sunitinib. Molina AM, Ginsberg MS, Motzer RJ.

Everolimus Urology TSSG Chair Authorisation: Date:


Version 3.2



INTERFERON (Roferon-A) (Renal) Indication: Advanced renal cell cancer

DRUG REGIMEN Week 1 ONLY Dose 1 & 2 INTERFERON 2α (Roferon) 4.5 million Units subcutaneous for the first TWO doses

ONLY either Mon, Wed or Fri in the evening

Dose 3 INTERFERON 2α (Roferon) 9 million Units subcutaneous either Mon, Wed or Fri in the evening

Week 2 onwards

Doses 1 - 3 INTERFERON 2α (Roferon) 9 million Units subcutaneous THREE times per week. Mon, Wed and Fri in the evening

Cycle Frequency: Continuous treatment dependent on tolerance and response with reviews every 2 - 3 months

DOSE MODIFICATIONS Reduce according to toxicity, discuss with Consultant or Registrar


Give Discuss

Hb x g/dL ≥10 < 10



CONCURRENT MEDICATION Paracetamol should be administered 1 hour prior to treatment

ANTI-EMETIC POLICY Non emetogenic


Interferon Roferon



Version 3.2



PAZOPANIB (Renal cell carcinoma) Indication: Treatment of advanced and/ or metastatic renal cell carcinoma. Nice guidance: Pazopanib is recommended as a first-line treatment option for people with advanced renal cell carcinoma: who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and if the manufacturer provides pazopanib with a 12.5% discount on the list price, and provides a possible future rebate linked to the outcome of the head-to-head COMPARZ trial, as agreed under the terms of the patient access scheme and to be confirmed when the COMPARZ trial data are made available.

DRUG REGIMEN Day 1 Pazopanib 800mg orally daily for 4 weeks Cycle Frequency: Daily for 4 weeks continuously until progression

DOSE MODIFICATIONS Pazopanib: Any dose modifications should be discussed with a Consultant.

Renal impairment No dose adjustment is required in patients with creatinine clearance above 30 ml/min. Caution is advised in patients with creatinine clearance below 30 ml/min as there is no experience of pazopanib in this patient population.

Hepatic impairment Administration of pazopanib to patients with mild or moderate hepatic impairment should be undertaken with caution and close monitoring due to potentially increased exposure to the medicinal product. Insufficient data are available in patients with mild hepatic impairment to provide a dose adjustment recommendation but a reduced pazopanib dose of 200 mg once daily is recommended in patients with moderate hepatic impairment. Pazopanib is contraindicated in patients with severe hepatic impairment.


Give Discuss

Hb x g/dL ≥10 < 10


Pazopanib Urology TSSG Chair Authorisation: Date:


Version 3.2



Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) Thyroid function tests Ask GP to monitor blood pressure on a regular basis, weekly initially 2) Non urgent tests Tests relating to disease response/progression



ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS REFERENCES 1. SPC February 2011 2. NICE guidance February 2011

Pazopanib Urology TSSG Chair Authorisation: Date:


Version 3.2



SUNITINIB (Renal cell carcinoma) Indication: Treatment of advanced and/ or metastatic renal cell carcinoma. Nice guidance: Sunitinib is recommended as a first-line treatment option for people with advanced and/or metastatic renal cell carcinoma who are suitable for immunotherapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

DRUG REGIMEN Day 1 Sunitinib 50mg orally daily for 4 weeks Cycle Frequency: Daily for 4 weeks then a 2 week rest period (6 week cycle)

DOSE MODIFICATIONS Sunitinib: Any dose modifications should be discussed with a Consultant.

Renal impairment No data available for use in impaired renal function

Hepatic impairment No dose adjustment is required in mild or moderate hepatic impairment. No data available for severe hepatic impairment


Give Discuss

Hb x g/dL ≥10 < 10


Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) Thyroid function tests Ask GP to monitor blood pressure on a regular basis, weekly initially 2) Non urgent tests Tests relating to disease response/progression

Sunitinib Urology TSSG Chair Authorisation: Date:

Page 1 of 2 Published: Review:

Version final





ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Skin - skin discolouration and depigmentation of the hair and skin may occur. Palmar / plantar syndrome Neutropenia Mouth pain / irritation / sensitivity may occur Haemorrhage – an increased risk of bleeding may occur. Hypertension – treatment induced hypertension. Sunitinib treatment should temporarily be suspended until hypertension is controlled. Gastrointestinal – serious gastrointestinal complications including gastrointestinal perforation have occurred rarely. Hypothyroidism REFERENCES 1. SPC September 2008 2. NICE guidance March 2009

Sunitinib Urology TSSG Chair Authorisation: Date:

Page 2 of 2 Published: Review:

Version final



MITOMYCIN C bladder installation weekly (Bladder)

Indications: Superficial bladder tumours

DRUG REGIMEN Day 1 MITOMYCIN C 40mg in 40-50ml water or sodium chloride 0.9% intravesically

Cycle frequency: Every 7 days for 6 cycles

DOSE MODIFICATIONS Urine dipsticks – if positive for nitrites, leucocytes, blood or protein then delay by 1 week.

INVESTIGATIONS Urine dipsticks




Intravesical mitomycin



Version 3.2



MITOMYCIN C bladder installation 14 day (Bladder)

Indication: Superficial bladder tumours DRUG REGIMEN Day 1 MITOMYCIN C 40mg in 40-50ml water or sodium chloride 0.9% intravesically Cycle frequency: Every 14 days for 6 cycles






Intravesical mitomycin 14



Version 3.2



MITOMYCIN C bladder installation post-op (Bladder)

Indication: Superficial bladder tumours post operatively

DRUG REGIMEN Day 1 MITOMYCIN C 40mg in 40-50ml water or sodium chloride 0.9% intravesically

Cycle frequency: Once only






Intravesical mitomycin post op



Version 3.2



BCG bladder installation (Bladder)

Indication: Superficial bladder tumours

DRUG REGIMEN Day 1 BCG 1 vial (12.5mg) in 50ml sodium chloride 0.9% intravesically

Cycle frequency: Every 7 days for 6 cycles






Intravesical BCG



Version 3.2



Pre-hydration and post-hydration regimens

Ensure adequate diuresis is obtained prior to administration and maintained during and after administration. 1. Inpatient

Pre 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours Give cisplatin in 1000ml volume over 4 hours Post 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours

NB 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 6 hours if oral intake is inadequate

2. Day case / Outpatient Pre 1L sodium chloride 0.9% + 20 mmol KCl + 8mmol MgSO4 infusion over 2 hours 100ml mannitol 20% infusion over 30 minutes Give cisplatin in 1000ml volume over 2 hours Post 1L sodium chloride 0.9% + 20 mmol KCl + 8mmol MgSO4 infusion over 2 hours

Hydration Urology TSSG Chair Authorisation: Date


Version 3.2

NB Furosemide 40mg may be added if required



Common toxicity criteria Toxicity 0 1 2 3 4

Allergic None Transient rash,

drug fever <38C

(100.4F)

Urticaria, drug

fever 38C

(100.4F) and/or asymptomatic bronchospasm

Symptomatic bronchospasm requiring parenteral medication(s) with or without urticaria; allergy related oedema / angioedema

Anaphylaxis

Alopecia Normal Mild hair loss Pronounced hair loss

- -

Anorexia None Loss of appetite Oral intake significantly decreased

Requiring IV fluids Requiring feeding tube or parenteral nutrition

Blood counts Neutrophils

Within normal limits

1.5x109/l - normal 1.0-1.4x109/l 0.5-0.9x109/l <0.5x109/l

Blood counts Haemoglobin


10.0g/dl – normal 8.0 9.9g/dl 6.5-7.9g/dl <6.5g/dl

Blood counts Platelets


75x109/l - normal 50-74x109/l 10-49x109/l <10x109/l

Blood counts White blood count


3.0x109/l - normal 2.0-2.9x109/l 1.0-1.9x109/l <1.0x109/l

Diarrhoea (patients with colostomy)

None Mild increase in loose, watery colostomy output compared with pre-treatment

Moderate increase in loose, watery colostomy output compared with pre-treatment, but not interfering with normal activity

Severe increase in loose, watery colostomy output compared with pre-treatment, interfering with normal activity

Physiologic consequences requiring intensive care, or haemodynamic collapse

Diarrhoea (patients without colostomy)

None Increase of <4 stools/day over pre-treatment

Increase of 4-6 stools/day, or nocturnal stools

Increase of 7 stools/day, or incontinence; or need for parenteral support for dehydration

Physiological consequences requiring intensive care, or haemodynamic collapse

Hand-foot skin reaction

None Skin changes or dermatitis without pain

Skin changes with pain, not interfering with function

Skin changes with pain, interfering with function

-

Hepatic – alk phos

UNL >ULN – 2.5x ULN >2.5 – 5.0xULN 5.0 – 20.0xULN >20.0XULN

Hepatic – bilirubin

UNL >ULN – 1.5x ULN >1.5 – 3.0xULN 3.0 – 10.0xULN >10.0XULN



Lethargy None Increased fatigue over baseline, but not altering normal activities

Moderate (decrease in performance status by level 1) or causing difficulty performing some activities

Severe (decrease in performance

status by 2 levels), or loss of ability to perform some activities

Bedridden or disabling

Nausea None Able to eat Oral intake significantly decreased

No significant intake, requiring IV fluids

-

Neuropathy - motor

Normal Subjective weakness but no objective findings

Mild objective weakness interfering with function, but not interfering with activities of daily living

Objective weakness interfering with activities of daily living

Paralysis

Neuropathy - sensory

Normal Loss of deep tendon reflexes or paresthesia (including tingling) but not interfering with function

Objective sensory loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living

Sensory loss of paresthesia interfering with activities of daily living

Permanent sensory loss that interferes with function

Pain None Mild pain not interfering with function

Moderate pain: pain or analgesics interfering with function but not interfering with activities of daily living

Severe pain: pain or analgesics severely interfering with activities of daily living

Disabling

Stomatitis None Painless ulcers, erythema or mild soreness

Painful erythema, oedema or ulcers but can eat or swallow

Painful erythema oedema, or ulcers requiring IV hydration

Severe ulceration or requires parenteral or enteral nutritional support or prophylactic intubation

Vomiting None 1 episode in 24 hours

2-5 episodes in 24 hours

6 episodes in 24 hours, or need for IV fluids

Requiring parenteral nutrition, or physiological consequences requiring intensive care; haemodynamic collapse

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