BLADDER CANCER / TRANSITIONAL CELL …

1 BLADDER CANCER -TCC Regimens Approved NWLCN BLADDER page 1 of 18 BLADDER CANCER / TRANSITIONAL CELL carcinoma Section by: Dr Philip Savage, Professor Jonathan Waxman, Dr Alison Falconer, Dr Simon Stewart. Version: BLADDER CANCER /TCC Regimens Approved NWLCN 15 Oct13 Section last updated: 15th October 2013 Section last corrected: 15th October 2013 Approved by Urology Lead Oncology Clinician: Dr P Savage Date Review date: October 2015 I N D E X Page Gemcitabine Regimens 1. Gemcitabine-1250/Cisplatin-70 D1+8 CTIS 1695 2 2. Gemcitabine-1000/Carboplatin 5 AUC D1+8 CTIS 134 4 Taxane regimens 3. Paclitaxel-80 weekly CTIS 1698 5 4. Gemcitabine/Cisplatin/Paclitaxel D1+8 Additional private care CTIS 1696 7 5. Gemcitabine/Carboplatin/Paclitaxel D1+8 Additional private care CTIS 1697 9 Other regimens 6.

2 CMV CTIS 187 11 7. MVAC CTIS 682 12 8. Vinflunine (Additional private care, no longer CDF) 14 BLADDER CANCER -TCC Regimens Approved NWLCN BLADDER page 2 of 18 BLADDER CANCER / TRANSITIONAL CELL carcinoma Section by: Dr Philip Savage, Professor Jonathan Waxman,Dr Alison Falconer, Dr Simon Stewart. Version: BLADDER CANCER -TCC Regimens Approved NWLCN 15 Oct13 Section last updated: 15th October 2013 Section last corrected: 15th October 2013 Approved by Urology Lead Oncology Clinician: October 2013 Review date: October 2015 Gemcitabine Regimens 1. Gemcitabine1250-Cisplatin70 D1+8 (CTIS: 1695) Gemcitabine 1250mg/m2 IV over 30 mins Day 1 and 8 Prehydrations Day 1 Cisplatin 70mg/m2 IV over 2 hrs Day 1 Post hydrations Day 1 Gemcitabine dose changed April 2011 October 2013; Some clinician dose in line with POUT Trial; Gemcitabine 1000mg/m2 Day 1 and 8 October 2013; Some clinicians split Cisplatin dose in line with POUT trial ie for GFR 50-70mls/min administer cisplatin as split dose: ie Cisplatin 35mg/m2 days 1 and 8 Interval between cycles: Repeat every 21 days Number of cycles: Neoadjuvant: 3 cycles Adjuvant: 4 cycles Metastatic: 6 cycles Tests before starting course of chemo: FBC, U&Es, LFTs, EDTA Adequate renal function (Crcl 60mls/min).

3 Tests to OK/Confirm each cycle of chemo: Day 1; FBC, U&Es, LFTs, Crcl (calculated). Consider repeating EDTA cycle 3. Day 8 FBC, U&Es Supportive drugs with each cycle: Antiemetics as per NWLCN guidelines below or as per local policy; Day 1; Very high risk antiemetics Day 8; Low risk anti-emetics Chlorhexidine mouthwash 10ml qds prn. Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book) NWLCN Chemotherapy alert card Macmillan drug specific information sheets and information prescriptions as appropriate NWLCN Neutropenia DVD Additional information: Administration notes: Gemcitabine: must be administered over 30 minutes. In case of injection site reaction/vein irritation, the infusion may be slowed down slightly, but must not be infused over more than one hour.

4 Prolonged infusion increases the treatment toxicity and should be avoided. Peripheral venous comfort may be increased by warming the arm with a heat pad. BLADDER CANCER -TCC Regimens Approved NWLCN BLADDER page 3 of 18 Cisplatin Weigh patient before and after cisplatin infusion or monitor urine output. If weight gain > or symptomatic of fluid retention: inform doctor, patient may require diuretics Dose modifications: See table Gem-Cisp: BLADDER below References: J. Clin Oncol 2000;18:3068-77 Van der Maase et al EORTC 30994 protocol BC CANCER Agency Protocol summary GUAVPG March 2011 dose modifications Table: Gem-Cisp BLADDER If day 8 chemo is delayed, omit day 8 chemo and restart day 22 once counts recovered. Side-effect Gem-Cisp BLADDER Dose Modification Source: GC vs MVAC Trial/BCCA Haematology Neutrophils Platelets x 109L x109/L Day 1 and 100 or 75-99 < or <75 Day 8 and 100 or 75-99 < or <75 Full dose all drugs Gemcitabine 25% dose reduction Cisplatin full dose Delay until recovered.

5 Discuss with consultant. Full dose all drugs Gemcitabine 25% dose reduction Do not give Neurotoxicity WHO Grade 0-1 Grade 2 Grade 3 Grade 4 All drugs; Full dose Gemcitabine: Full dose Cisplatin: 50% dose reduction Gemcitabine: 50% dose reduction or omit Cisplatin: Omit Gemcitabine: 50% dose reduction or stop Cisplatin: Stop Renal Toxicity Crcl 60mls/min 50-59mls/min <50mls/min Creatinine WHO grade 0-2 3 (>5 x ULN) Cisplatin: Full dose Cisplatin: Check with consultant. Consider split dose of cisplatin ie. administer 35mg/m2 on day 1 and day 8 Cisplatin: Omit Gemcitabine: Full dose Gemcitabine: Omit Ototoxicity Tinnitus or significant clinical hearing loss: Reduce or stop Cisplatin. BLADDER CANCER -TCC Regimens Approved NWLCN BLADDER page 4 of 18 2.

6 Gemcitabine1000-Carboplatin 5 AUC D1+8 (CTIS: 134) Gemcitabine 1000mg/m2 IV over 30 mins Day 1 and 8 Carboplatin 5(GFR+25)mg IV over 1 hour Day 1 Interval between cycles: Repeat day 21 (for patients unable to tolerate Gemcitabine/cisplatin) Number of cycles: Neoadjuvant: 3 cycles Adjuvant: 4 cycles Metastatic: 6 cycles Tests before starting course of chemo: FBC, U&Es, LFTs, EDTA, adequate renal function (Cr 50mls/min) or discuss with consultant. Tests to OK/Confirm each cycle of chemo: Day 1; FBC, U&Es, LFTs, Crcl (calculated), Consider repeating EDTA after cycle 3. Day 8: FBC, U&Es Supportive drugs with each cycle: Antiemetics as per NWLCN guidelines as below or as per local policy; Day 1; High risk antiemetics Day 8; Low risk antiemetics Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book) NWLCN Chemotherapy alert card Macmillan drug specific information sheets and information prescriptions as appropriate NWLCN Neutropenia DVD Additional information: Administration notes: Gemcitabine administration notes; see page 2 Carboplatin Hypersensitivity Reactions Carboplatin may cause allergic reactions which can occur within minutes of administration.

7 See below for SPC information. If any reaction occurs: stop the 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. Carboplatin SPC (Hospira (09 June 2009): Infrequent allergic reactions to carboplatin have been reported, erythematous rash, fever with no apparent cause or pruritus. Rarely, anaphylaxis, angio oedema and anaphylactoid reactions including bronchospasm, urticaria and facial oedema have occurred. These reactions are similar to those observed after administration of other platinum containing compounds and may occur within minutes. The incidence of allergic reactions may increase with previous exposure to platinum therapy; however, allergic reactions have been observed upon initial exposure to carboplatin.)

8 Patients should be observed carefully for possible allergic reactions and managed with appropriate therapy, including antihistamines, adrenaline and/or glucocorticoids. Dose modifications: See table Gem-Carbo BLADDER table page 5 References: Carboplatin substitution. J. Clin Oncol 2000;18:3068 Van der Maase et al BLADDER CANCER -TCC Regimens Approved NWLCN BLADDER page 5 of 18 Table: Gem-Carbo BLADDER If day 8 chemo is delayed then omit day 8 chemo and restart next cycle day 22 once counts recovered Side-Effect Gem-Carbo BLADDER Dose Modification (Dr P Savage) Haematology Neutrophils Platelets x109/L x 109/L Day 1 and 100 < or <100 Day 8 and 75 < or <75 Full dose all drugs Wait until recovery. Discuss with consultant. Consider Gemcitabine: 20% dose reduction day 1 and 8 Carboplatin: 20% dose reduction day 1 Wait until recovery and discuss with consultant Gemcitabine day 8 full dose Do not give day 8 and restart next cycle of chemotherapy on day 22 Renal Function 30mls/min < 30mls/min Dose as per Calvert formula Do not give.

9 Discuss with consultant Taxane Regimens 3. Paclitaxel-80 Weekly (CTIS: 1698) Dexamethasone 8mg* IV bolus 30minutes before paclitaxel Day 1 Chlorphenamine 10mg IV bolus 30minutes before paclitaxel Day 1 Ranitidine 50mg IV bolus 30 minutes before paclitaxel Day 1 Paclitaxel 80mg/m2 IV over 1 hour Day 1 *Cycle 2 onward dexamethasone may be reduced to 4mg if no problems with first cycle at 8mg Interval between cycles: Repeat every 7 days Number of cycles: Relapsed BLADDER 6 cycles Tests before starting course of chemo: FBC, U&Es, LFTs Tests to OK/Confirm each cycle of chemo: FBC, U&Es, LFTs Supportive drugs with each cycle: Moderate risk antiemetics as per NWLCN guidelines or as per local policy Dexamethasone pre-medication as above Patient information.

10 Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book) NWLCN Chemotherapy alert card Macmillan drug specific information sheets and information prescriptions as appropriate NWLCN Neutropenia DVD Additional information: Administration notes: Paclitaxel: Use administration set (polyethylene lined with inline filter microns) provided by pharmacy only for paclitaxel. Acute hypersensitivity reactions can occur, observe closely especially during the first two cycles. BLADDER CANCER -TCC Regimens Approved NWLCN BLADDER page 6 of 18 Hypersensitivity Reactions Paclitaxel Hypersensitivity Reactions Paclitaxel may cause allergic reactions. See below for SPC information. If any reaction occurs: stop the infusion and discuss with consultant After discussion with consultant: Mild reactions rash: May consider re-challenge after discussion with consultant.