Chapter 10: Urological Cancer

Contents Chapter 10: Urological Cancer ...... 1 Bladder Cancer - Transitional cell ...... 2 Neoadjuvant ...... 2 Cisplatin / gemcitabine ...... 2 Cisplatin / gemcitabine split dose ...... 2 Concurrent Chemotherapy / Radiotherapy ...... 3 Mitomycin C and fluorouracil ...... 3 Cisplatin ...... 3 Advanced ...... 4 Cisplatin / gemcitabine split dose ...... 4 Cisplatin / gemcitabine ...... 4 Carboplatin / gemcitabine ...... 5 Paclitaxel ...... 5 Renal cancer ...... 6 Advanced: ...... 6 First line ...... 6 Sunitinib ...... 6 Pazopanib ...... 6 *Temsirolimus...... 7 Second line therapy ...... 8 *Everolimus (Afinitor®) ...... 8 *Axitinib ...... 8 Prostate Cancer ...... 10 Docetaxel ...... 10 Weekly Docetaxel ...... 10 *Abiraterone First line therapy ...... 11 Second line treatment ...... 11 Mitoxantrone ...... 11 Abiraterone ...... 12 *Cabazitaxel ...... 13

Issue Date: June 2014 Page 1 of 13 Issue No: 11.10.0 Author: Helen Flint Authorised by: Dr I Syndikus Copy No:

Bladder Cancer - Transitional cell

Neoadjuvant

Cisplatin / gemcitabine

Cisplatin/gemcitabine Frequency Course length Every 21 Days 3 cycles Drug Dose Admin Day 1 Cisplatin 70mg/m2 IV infusion over 90 minutes

Day 1 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Day 8 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Laboratory investigations  Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle, normal FBC limits for administration apply

Cisplatin / gemcitabine split dose

Cisplatin/gemcitabine Frequency Course length Every 21 Days Upto 4 cycles Drug Dose Admin Day 1 Cisplatin 35mg/m2 IV infusion over 60 minutes Day 1 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Day 8 Cisplatin 35mg/m2 IV infusion over 60 minutes

Day 8 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Laboratory investigations  Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle, normal FBC limits for administration apply

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Concurrent Chemotherapy / Radiotherapy

Mitomycin C and fluorouracil

Mitomycin C and fluorouracil Frequency Course length Five week course One course Drug Dose Admin Day 1 Mitomycin C 12mg/m2 IV bolus (maximum dose 20mg) Days 1 to 5 Fluorouracil 500mg/m2 daily IV infusion over 24 hours

Days 16 to 20 Fluorouracil 500mg/m2 daily IV infusion over 24 hours

Laboratory investigations  Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply

Cisplatin

Cisplatin Frequency Course length Every 7 Days 4 to 6 weeks, concurrent with radiotherapy Drug Dose Admin

2 IV infusion over 60 minutes Day 1 Cisplatin 30 to 40mg/m IV (maximum dose 60mg)

XRT 55Gy in 20# (4 x weekly cisplatin infusions) or XRT 64Gy in 32# (6 x weekly cisplatin infusions) As possible alternative to standard mitomycin C and fluorouracil

Laboratory investigations  Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply

Issue Date: June 2014 Page 3 of 13 Issue No: 11.10.0 Author: Helen Flint Authorised by: Dr I Syndikus Copy No:

Advanced

Cisplatin / gemcitabine split dose

Cisplatin/gemcitabine Frequency Course length Every 21 Days Upto 4 cycles Drug Dose Admin Day 1 Cisplatin 35mg/m2 IV infusion over 60 minutes Day 1 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Day 8 Cisplatin 35mg/m2 IV infusion over 60 minutes

Day 8 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Laboratory investigations  Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply

Cisplatin / gemcitabine

Cisplatin/gemcitabine Frequency Course length Every 21 Days Upto 6 cycles Drug Dose Admin Day 1 Cisplatin 70mg/m2 IV infusion over 90 minutes Day 1 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Day 8 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Laboratory investigations  Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply

Issue Date: June 2014 Page 4 of 13 Issue No: 11.10.0 Author: Helen Flint Authorised by: Dr I Syndikus Copy No:

Carboplatin / gemcitabine

Carboplatin/gemcitabine Frequency Course length Every 21 Days Upto 6 cycles Drug Dose Admin Day 1 Carboplatin AUC 4 to 5 IV infusion over 60 minutes

Day 1 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

Day 8 Gemcitabine 1000mg/m2 IV infusion over 30 minutes

For patients with impaired renal function Interval between cycles can be increased to 28 days if prolonged immunosuppression

Laboratory Investigation  Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if clinically indicated  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle, normal FBC limits for administration apply

Paclitaxel

Weekly paclitaxel Frequency Course length Every 7 days Until disease progression Drug Dose Admin Day 1 Chlorphenamine 10mg IV bolus IV bolus Day 1 Dexamethasone 8mg Reducing to 4mg from week 2 Day 1 Ranitidine 50mg IV bolus

Day 1 Paclitaxel 80mg/m2 IV infusion over 60 minutes

Laboratory investigations  Ensure normal renal function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Patients with abnormal hepatic function should be treated cautiously  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle.  Normal limits for administration apply

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Renal cancer

See also: http://www.mccn.nhs.uk/userfiles/documents/Renal%20Cancer%20Guidelines.pdf

Advanced:

First line

Sunitinib

Sunitinib Frequency Course length Every 42 days Until disease progression Drug Dose Admin Orally, daily for 4 weeks, followed by a two Days 1 to 28 Sunitinib 50mg daily week break

OR

Pazopanib

Pazopanib Frequency Course length Continuous Until disease progression Drug Dose Admin Daily Pazopanib 800mg daily Orally, daily

Laboratory Investigations  Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated. Where renal / hepatic function are abnormal treatment is at physician discretion  Weekly blood pressure monitoring initially  Thyroid function tests  FBC prior to each cycle, normal limits for administration apply

Interferon Alpha Interferon by s/c injection: (Intron) Week 1 Mon 5 million units Wed 5 million units Fri 10 million units Weeks 2+ 10 million units Mon / Wed / Fri

Patients should have 2 out of 3 following criteria: PS 0-1 Relapse post nephrectomy > 12 months Low volume disease

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Laboratory Investigations  Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle. Normal FBC limits for administration apply

*Temsirolimus

Temsirolimus Frequency Course length Every 7 days Until disease progression Drug Dose Admin Day 1 Chlorphenamine 10mg IV bolus Day 1 Temsirolimus 25mg IV infusion over 30 to 60 minutes

Laboratory Investigations  Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply

*NB available via the Cancer Drugs Fund CDF Criteria (as at 14th May 2014) The treatment of advanced renal cell carcinoma where all the following criteria are met: 1. Application made by and first cycle of systemic anti-cancer therapy to be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy 2. Renal cell carcinoma 3. 1st line indication 4. Poor risk patients (at least 3 of 6 prognostic risk factors)

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Second line therapy

*Everolimus (Afinitor®)

Everolimus Frequency Course length Continuous Until disease progression Drug Dose Admin Daily Everolimus 10mg daily Orally, daily

Laboratory Investigations  Ensure normal renal and hepatic function prior to each cycle 1  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply  Random blood sugar / lipid profile *NB available via the Cancer Drugs fund CDF Criteria (as at 14 May 2014) The treatment of advanced renal cell carcinoma where all the following criteria are met:

1. Application made by and first cycle of systemic anti-cancer therapy to be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy 2. Biopsy proven renal cell carcinoma 3. Use in patients: - who have previously been treated with VEGF targeted agent OR - with intolerance or contraindications to a VEGF inhibitor

*Axitinib

Axitinib Frequency Course length Continuous Until disease progression Drug Dose Admin Daily Axitinib 5mg BD initially Orally, twice daily

Patients not on anti-hypertensives when axitinib is started: After 4 weeks, for patients who tolerate this dose with no severe adverse reactions and whose blood pressure remains ≤ 150/90 mmHg without the need for antihypertensives, the dose may be increased to 7mg twice daily. Subsequently, using the same criteria above, patients who tolerate the 7 mg bd dose without the need for an antihypertensive may have their dose increased to a maximum 10 mg twice daily.

Patients on anti-hypertensive therapy before axitinib is started: After 4 weeks, for patients who tolerate the 5mg bd dose with no severe adverse reactions and whose blood pressure remains stable and ≤ 150/90 mmHg without the need for an increase in anti-

Issue Date: June 2014 Page 8 of 13 Issue No: 11.10.0 Author: Helen Flint Authorised by: Dr I Syndikus Copy No:

hypertensive therapy, the dose may be increased to 7mg twice daily. If in doubt, discuss with Consultant. Subsequently, using the same criteria above, patients who tolerate the 7 mg bd dose without the need for an increase in antihypertensive therapy may have their dose increased to a maximum of 10 mg twice daily.

*NB available via the Cancer Drugs fund CDF Criteria (as at 14th May 2014) The treatment of advanced renal cell carcinoma where all the following criteria are met: 1. Application made by and first cycle of systemic anti-cancer therapy to be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy 2. Histologically or cytologically confirmed renal cell carcinoma

3. Patient progressed after only 1st line cytokine or after only one line of treatment with a tyrosine kinase inhibitor

Issue Date: June 2014 Page 9 of 13 Issue No: 11.10.0 Author: Helen Flint Authorised by: Dr I Syndikus Copy No:

Prostate Cancer

Docetaxel

Docetaxel / prednisolone Frequency Course length Every 21 Days Upto 10 cycles Drug Dose Admin Orally for 3 days, commencing 24 hours Dexamethasone 8mg BD before docetaxel Day 1 Docetaxel 75mg/m2 IV infusion over 60 minutes Days 1 to 21 Prednisolone 10mg daily Orally, each morning

Reassessment after 2 cycles and continue to a maximum of 10 only if responding or stable disease.

Criteria: WHO Performance Status 0-1 Hormone resistant

If unable to tolerate 3 weekly regimen, then consider weekly docetaxel:

Weekly Docetaxel

Docetaxel / prednisolone Frequency Course length Every 7 days, for 5 out of 6 weeks Up to 5 cycles Drug Dose Admin Day 1 Dexamethasone 8mg IV bolus, one hour before docetaxel Day 1 Docetaxel 30mg/m2 IV infusion over 30 minutes

Days 1 to 21 Prednisolone 10mg daily Orally, each morning

Docetaxel administered on days 1, 8, 15, 22 and 29 of a 42 day (6 week) cycle.

Laboratory Investigations  Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply

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*Abiraterone - First line therapy

Abiraterone and prednisolone Frequency Course length Continuous Until disease progression Drug Dose Admin Daily Abiraterone 1000mg daily Orally, daily Orally, each morning until completion of Daily Prednisolone 10mg daily chemotherapy.

Dexamethasone 500 micrograms can be substituted for the prednisolone *NB available via the Cancer Drugs fund CDF Criteria (as at 14 May 2014) The treatment of castrate-resistant metastatic prostate cancer where all the following criteria are met: 1. Application made by and first cycle of systemic anti-cancer therapy to be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy 2. Castrate-resistant metastatic prostate cancer 3. Chemotherapy naïve for metastatic disease 4. PS 0 or 1 5. Asymptomatic or mildly symptomatic patients 6. Chemotherapy not yet indicated

Second line treatment

Mitoxantrone

Mitoxantrone Frequency Course length Every 21 days 6 cycles Drug Dose Admin Day 1 Mitoxantrone 12mg/m2 IV bolus (maximum single dose 20mg)

Maximum total/cumulative dose 140mg/m2

Criteria Endocrine refractory disease PS 0-1 Normal FBC, renal, liver function No cardiac failure Laboratory Investigations  Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle, normal FBC limits for administration apply

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*Enzalutamide Enzalutamide Frequency Course length Continuous Until disease progression Drug Dose Admin Daily Enzalutamide 160mg daily Orally, daily

*NB available via the Cancer Drugs fund CDF Criteria (as at 14 May 2014) The treatment of castrate-resistant metastatic prostate cancer where all the following criteria are met: 1. Application made by and first cycle of systemic anti-cancer therapy to be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy 2. Castrate-resistant metastatic prostate cancer 3. Progressive disease following docetaxel chemotherapy 4. PS 0 -2 5. No previous treatment with abiraterone before or after docetaxel

Abiraterone – second line treatment

Abiraterone and prednisolone Frequency Course length Continuous Until disease progression Drug Dose Admin Daily Abiraterone 1000mg daily Orally, daily Orally, each morning until completion of Daily Prednisolone 10mg daily chemotherapy.

Dexamethasone 500 micrograms can be substituted for the prednisolone

Criteria Castrate resistant Prior docetaxel chemotherapy

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*Cabazitaxel

Cabazitaxel and prednisolone Frequency Course length Every 21 days Upto 10 cycles Drug Dose Admin Day 1 Chlorphenamine 10mg IV bolus

Day 1 Dexamethasone 16mg IV bolus

Day 1 Ranitidine 50mg IV bolus Day 1 Cabazitaxel 25mg/m2 IV infusion over 60 minutes Orally, each morning until completion of Daily Prednisolone 10mg daily chemotherapy.

*NB available via the Cancer Drugs fund CDF Criteria (as at 14th May 2014) The treatment of castrate-resistant metastatic prostate cancer where all the following criteria are met: 1. Application made by and first cycle of systemic anti-cancer therapy to be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy 2. Castrate-resistant metastatic prostate cancer

3. Previous treatment with docetaxel based regimens

Laboratory Investigations  Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated  Where renal / hepatic function are abnormal treatment is at physician discretion  FBC prior to each cycle  Normal FBC limits for administration apply

Issue Date: June 2014 Page 13 of 13 Issue No: 11.10.0 Author: Helen Flint Authorised by: Dr I Syndikus Copy No: