germ cell regimens approved v4.02 nwlcn 29oct13.pdf

Germ Cell regimens Approved v4.02 NWLCN 29Oct13.doc Urology GCT page 1 of 22

GERM CELL TUMOURS Section by: Dr Philip Savage and Professor Michael Seckl Version: Germ Cell Tumour Regimens Approved 4.02 NWLCN 29Oct13 Section last updated: 17th October 2013 Last Corrected: 29th October 2013 Approved by Oncology GCT Lead Clinician: Dr Philip Savage Date Review date: October 2015

Page Treatment Options by IGCCC Prognostic Group Adjuvant Carboplatin 7AUC CTIS: 1103 2 BEP 5 day D1+8+15 CTIS: 817 3 First Line Good prognosis BEP 5day D1+8+15 CTIS: 817 3 EP 100/20 5day CTIS: 1106 7 Renal impairment CEB CTIS: 1124 6 Intermediate prognosis BEP 5day, D1+8+15 CTIS: 817 3 T-BEP D1+8+15 4 POMB/ACE CTIS: 60/61 8 Poor prognosis BEP 5day D1+8+15 CTIS: 817 3

POMB/ACE CTIS: 60/61 8 Poor prognosis plus Cerebral mets EP/OMB/ITMTX CTIS: 63/62/782 9 Emergency treatment EP 100/20 1 day CTIS: 64 10 2 day CTIS: 66/1513 10 3 day CTIS: 69 10 Second/Subsequent Line

TIP CTIS: 1120 11 PACE/PAC-PLAT CTIS: 648 / 641 12 GCP (ovarian GCT) CTIS: 1104 13 VelP CTIS: 632 15 Oxaliplatin-Gemcitabine CTIS: 1700 16 Etoposide 50mg/m2 oral CTIS: 1699 18

Under Consultant Direction Only Etoposide 500/Cisplat60 CTIS: 18 Cisplatin weekly/Etoposide CTIS: 1835 19 followed by Etoposide 50mg/m2 oral CTIS: 1699 20


GERM CELL TUMOURS Section by: Dr Philip Savage and Professor Michael Seckl Version: Germ Cell Tumour Regimens Approved v4.02 NWLCN 29Oct13 Section last updated: 17th October 2013 Last Corrected: 29th October 2013 Approved by Oncology GCT Lead Clinician: October 2013 Review date: October 2015 GERM CELL TUMOURS Teratoma/Seminoma 1. Carboplatin 7AUC (CTIS: 1103)

Carboplatin 7x(GFR+25)mg IV over 1 hour Day 1

Interval between cycles: one cycle only. No repeats Number of cycles: Adjuvant seminoma: one cycle only. No repeats Tests prior to single cycle of chemo: FBC, U&Es, LFTs, EDTA, CT TAP; Sperm storage

if wished. GFR � 40mls/min. If < 40mls/min discuss with

consultant. Neutrophils � 1.0 x 109/L and Platelets � 80 x

109/L. If below these levels discuss with consultant.

Supportive drugs: High risk antiemetics as per NWLCN guidelines or as per local policy

Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book) NWLCN Chemotherapy alert card

Macmillan drug specific information sheets/information prescription as appropriate NWLCN Neutropenia DVD

Additional information: Carboplatin Hypersensitivity Reactions Carboplatin may cause allergic reactions, which can occur within minutes of administration see below for SPC information. If any reaction occurs: stop infusion and discuss with consultant. After discussion with consultant; Mild reactions eg rash; May consider re-challenge after discussion with

consultant Severe reactions Do not re-challenge, discuss with consultant Carboplatin SPC (Hospira 09 June 2009). Infrequent allergic reactions to carboplatin have been reported, e.g. 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. Patients should be observed carefully for possible allergic reactions and managed with appropriate therapy, including antihistamines, adrenaline and/or glucocorticoids

Dose modifications: Dose as per GFR. Do not give if GFR below 40mls/min

Reference: Lancet 2005;366 (9482):293-300 Oliver RT et al 2. BEP 5day +D8 +D15 (CTIS: 817) Etoposide 100mg/m2 IV over 1 hour Days 1 to 5 Prehydrations Days 1 to 5 Cisplatin 20mg/m2 IV over 2 hours Days 1 to 5 Post hydrations Days 1 to 5 Hydrocortisone 100mg IV 30-60 minutes before bleomycin Day 2, 8 and 15 Chlorphenamine 10mg IV 30-60 minutes before bleomycin Day 2, 8 and 15 Paracetamol 1gram oral, 30-60 minutes before bleomycin Day 2, 8 and 15 Bleomycin* 30,000iu IV over 6 hours Day 2, 8 and 15 Interval between cycles: Repeat every 21 days Number of cycles: Adjuvant: 2 cycles only Good prognosis: 3 cycles Intermediate prognosis: 4 cycles Poor prognosis; 4 cycles Test prior to course of chemo: FBC, U&Es, Mg, LFTs, EDTA (repeat prior

to cycle 3); Sperm storage if time permits; Respiratory function tests (and repeat prior to cycle 3); CT TAP; MRI brain. Aim to avoid routine antiemetic steroids,

Tests to OK/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs. Repeat EDTA if rising creatinine




Additional Information: *Bleomycin may be administered either on day 1 or 2 If GCSF support is required with this regimen, GCSF should be started on day 6 (24hours after the end of day 5 chemotherapy) and should continue as prescribed. Bleomycin may be administered on day 9 even if GCSF has been or is still being prescribed

Dose modifications: See BEP table page 4 Reference: Advanced Disease. Lancet 2001;357:739-745. Toner GC et al Adjuvant: J.Clin Oncol 1996;14(2):441-448. Pont J et al


Table: BEP Due to curative aim of treatment, dose modifications should be avoided and only made after discussion with and under direction of the consultant in charge. However, where a dose reduction is to be made the following may serve as guidance: Side effect; BEP-GCT Dose Modification (Source: )

Haematology Neutrophils Platelets x109/L x109/L �1.0 and �80

Full dose If counts below these limits delay and discuss with consultant. Consider GCSF to support subsequent cycles (discuss with consultant)

Renal function �60mls/min EDTA <60ml/min

<50ml/min

<30ml/min

Full dose Discuss with consultant, consider changing to carboplatin using the CEB regimen, or dose reduce Cisplatin. As above plus Omit bleomycin Discuss with consultant

Hepatic Impairment Bilirubin � ULN >ULN

Full dose Discuss with consultant

Pulmonary Toxicity

If bleomycin pulmonary toxicity (BPT) is suspected, stop bleomycin. Whilst there is no accurate test to predict who is likely to get this problem, it is more likely to occur in smokers, those aged over 40 years, those with poor renal function and those with previous RT treatment. Generally BPT presents after the end of chemotherapy treatment.

3. T-BEP Day 1,8,15 Dexamethasone 20mg Oral* 12 hours pre-paclitaxel Day 1 Dexamethasone 20mg Oral* 3-6 hours pre-paclitaxel Day 1 Ranitidine 50mg IV bolus 30-60mins pre-paclitaxel Day 1 Chlorphenamine 10mg IV bolus 30-60mins pre-paclitaxel Day 1 Paclitaxel 175mg/m2 IV over 3 hours Day 1 Etoposide 100mg/m2 IV over 1 hour Days 1 to 5 Cisplatin 20mg/m2 IV over 4 hours Days 1 to 5 Sodium chloride 0.18%, Glucose 4% plus 20mmols Kcl + 4grams MgSO4 1L IV over 8 hours Days 1 to 5 Sodium chloride 0.18%, Glucose 4% plus 20mmols Kcl + 4grams MgSO4 1L IV over 8 hours Days 1 to 5 Hydrocortisone 100mg IV 30-60 minutes before bleomycin Day 2, 8 and 15 Chlorphenamine 10mg IV 30-60 minutes before bleomycin Day 2, 8 and 15 Paracetamol 1gram oral, 30-60 minutes before bleomycin Day 2, 8 and 15 Bleomycin 30,000iu IV Over 30 minutes Days 2, 8,15 Neulasta 6mg SC 24 hours after end of last cisplatin infusion


*Dexamethasone premed may be changed to a single dose dexamethasone 20mg IV bolus 30-60minutes pre paclitaxel

Interval between cycles: Repeat every 21 days Number of cycles: Intermediate prognosis: 4 cycles Test prior to course of chemo: : FBC, U&Es, Mg, LFTs, EDTA (repeat prior

to cycle 3); Sperm storage if time permits; Respiratory function tests (and repeat prior to cycle 3); CT TAP; MRI brain. Aim to avoid routine antiemetic steroids,

Tests to OK/Confirm each cycle of chemo: FBC, U&Es, Mg, LFTs. Repeat EDTA if rising creatinine

Supportive drugs: High risk antiemetics as per NWLCN guidelines or as per local policy. GCSF as above



Additional Information: Magnesium Supplementation Trial protocol required all patients to receive supplementation of 8 grams MgSO4 IV per day to avoid cases of severe hypomagnesaemia observed during T-BEP dose finding study (Mg <0.4mmols/L despite 6 grams MgSO4/day).

Administration notes Paclitaxel; must be administered via a PVC free giving set. Polypropylene or polyolefin lined paclitaxel giving set with 0.22 micron inline filter will be provided by pharmacy if requested. Vital signs should be monitored for 1st hour of paclitaxel infusion on all cycles. Hypersensitivity Reactions Paclitaxel Hypersensitivity Reactions Paclitaxel may cause allergic reactions, see below for SPC information. If any reaction occurs: stop infusion and discuss with consultant. After discussion with consultant; Mild reactions eg rash: May consider re-challenge after discussion with consultant Severe reactions Do not re-challenge, discuss with consultant. Paclitaxel SPC (Hospira 31 Nov 2010). Significant hypersensitivity reactions: As characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticarial have occurred in <1% of patients receiving paclitaxel after adequate premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately, symptomatic therapy should be initiated and the patient should not be rechallenged with paclitaxel. Macrogolglycerol ricinoleate (polyoxyl castor oil), an excipient of this medicinal product, can cause these reactions.

Dose Modifications: Discuss with Consultant. Original protocol dose reductions can be found at http://jco.ascopubs.org/content/30/8/792/suppl/DC1

Reference: JCO 2012; 30(8):792-799. Ronald De Wit et al


4. CEB (CTIS: 1124) Etoposide 120mg/m2 IV over 1 hour Days 1,2 and 3 Carboplatin 5x(GFR+25)mg* IV over 1 hour Day 1 Hydrocortisone 100mg IV 30-60 minutes before bleomycin Day 2 Chlorphenamine 10mg IV 30-60 minutes before bleomycin Day 2 Paracetamol 1gram oral, 30-60 minutes before bleomycin Day 2 Bleomycin 30,000iu IV over 6 hours Day 2 *5x(GFR+25) if EDTA or if calculated Crcl reduce dose by 10%.

*Carboplatin dose in original trial was escalated if Day 16 platelets >150 x 109/L and WBC >1.5 x 109/L. Inferior to cisplatin based BEP, only use if unable to tolerate cisplatin

Interval between cycles: Repeat every 21 days Number of cycles: Poor renal function unable to tolerate cisplatin: 4 cycles Tests prior to course of chemo: FBC, U&Es, Mg, LFTs, EDTA (repeat prior

to 3rd cycle), CT TAP, MRI brain. Sperm storage if time permits. Respiratory function tests if indicated.

Aim to avoid routine steroid anti-emetics, Tests to ok/confirm each cycle of chemo: FBC, U&Es, Mg, LFTs. Repeat EDTA if

rising creatinine Supportive drugs: High risk antiemetics as per NWLCN guidelines or as per local

policy Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book) NWLCN Chemotherapy alert card

Macmillan drug specific information sheet/information prescription as appropriate NWLCN Neutropenia DVD

Additional information: Dose modifications: See CEB table below Reference: J. Clin Oncol 1997;15(5):1844-1852. Horwich A et al Table: CEB Due to curative aim of treatment, dose modifications should be avoided and only made after discussion with and under direction of the consultant in charge. However, where a dose reduction is to be made the following may serve as guidance: Side effect; CEB-GCT Dose Modification (Source: )


Full dose If counts below these limits delay and discuss with consultant. Consider GCSF to support subsequent cycles/escalated back at full dose (discuss with consultant)

Renal function EDTA �60ml/min

<60ml/min <50ml/min

Full dose Calculate carboplatin dose using Calvert equation Omit bleomycin


Side effect; CEB-GCT Dose Modification (Source: )

<30ml/min

Carboplatin dose as above Discuss with consultant

Hepatic Impairment Bilirubin �ULN >ULN


Pulmonary Toxicity

If bleomycin toxicity (BPT) is suspected stop bleomycin. Whilst there is no accurate test to predict who is likely to get this problem, it is more likely to occur in smokers, those aged over 40 years, those with poor renal function and those with previous RT treatment. Generally BPT presents after the end of chemotherapy treatment.

5. EP-100/20 5 day (CTIS: 1106) Etoposide 100mg/m2 IV over 1 hour Days 1,2,3,4,5 Prehydrations Days 1,2,3,4,5 Cisplatin 20mg/m2 IV over 2 hours Days 1,2,3,4,5 Post hydrations Days 1,2,3,4,5 Interval between cycles: Repeat every 21 days Number of cycles: Good prognosis 4 cycles

Tests prior to course of chemo: FBC, U&Es, Mg, LFTs; Crcl/EDTA (repeat prior to cycle 3); CT TAP; MRI brain. Sperm storage if time permits; Aim to avoid routine antiemetic steroids.

Tests to ok/confirm each cycle of chemo: FBC, U&Es, Mg, LFTs. Repeat EDTA if rising creatinine

Supportive drugs High risk antiemetics as per NWLCN guidelines or as per local policy



Additional information: Dose modifications: Discuss with consultant

Reference: J. Clin Oncol 1988;6(8):1231-1238. Bosl GJ et al

Table: EP-GCT Due to curative aim of treatment, dose modifications should be avoided and only made after discussion with and under direction of the consultant in charge. However, where a dose reduction is to be made the following may serve as guidance: Side effect; EP-GCT Dose Modification Haematology Neutrophils Platelets x109/L x109/L �1.0 and �80

Full dose If counts below these limits delay and discuss with consultant.


Side effect; EP-GCT Dose Modification Consider GCSF to support subsequent cycles/escalated back at full dose (discuss with consultant)

Renal function EDTA �60mls/min

<60ml/min

<50ml/min <30ml/min

Full dose Consider changing to carboplatin calculating dose using Calvert equation or dose reduce cisplatin As above plus Etoposide: 25% dose reduction Discuss with consultant

Hepatic Impairment Bilirubin �ULN >ULN


6. POMB/ACE

Chemo every two weeks beginning with POMB, POMB, ACE, POMB, ACE etc. 6a. POMB (CTIS: 60) Vincristine 1mg/m2 (max 2mg) IV in minibag over 10mins Day 1 Methotrexate 300mg/m2 IV over 12 hours Day 1 Hydrocortisone 100mg IV 30-60 minutes before bleomycin Day 2 Chlorphenamine 10mg IV 30-60 minutes before bleomycin Day 2 Paracetamol 1gram oral, 30-60 minutes before bleomycin Day 2 Bleomycin 15,000iu IV over 12 hours Day 2 Bleomycin 15,000iu IV over 12 hours Day 2 Folinic acid 15mg Oral/IV at 24, 36, 48 and 60 hours after start of methotrexate Pre-hydrations Day 3 Cisplatin 40mg/m2 IV over 4 hours Day 3 Cisplatin 40mg/m2 IV over 4 hours Day 3 Cisplatin 40mg/m2 IV over 4 hours Day 3 Post hydrations Day 3 6b. ACE (CTIS: 61)

Etoposide 100mg/m2 IV over 30mins-1 hour Day 1, 2, 3 Actinomycin-D 0.5mg IV bolus Day 1, 2, 3 Cyclophosphamide 500mg/m2 IV over 30mins-1 hour Day 3 Interval between cycles: Chemo every 2 weeks beginning POMB, POMB, ACE POMB, ACE, POMB etc.

Alternate every two weeks with ACE (see above) ie: POMB every 28 days

Number of cycles: Intermediate prognosis: 5 cycles (ie P.P.A.P.A.) or to marker normalisation plus 2 cycles Poor prognosis: 7 cycles (ie. P.P.A.P.A.P.A.) or to Marker normalisation plus 2 cycles

Tests before starting course of chemo: FBC, U&E, Mg, LFTs, EDTA (repeat prior to cycle 3); CT TAP; MRI brain; Sperm storage if time permits; Respiratory function tests (and repeat prior to cycle 3). Aim to avoid routine antiemetic steroids.



Supportive drugs: Antiemetics below as per NWLCN guidelines or as per local policy

POMB ; Very high risk anti-emetics ACE; Moderate risk anti-emetics.


Macmillan drug specific information sheets /information prescription as appropriate NWLCN Neutropenia DVD

Additional information: Dose modifications: Discuss with consultant Reference: Ann. Oncol. 1997;8(5):477-83. Bower M et al.

7. Poor Prognosis Plus Cerebral Metastases at Presentation EP/OMB – MTX 1gram + Intrathecal Methotrexate EP 150/75 (CTIS: 63)

Etoposide 150mg/m2 IV over 30mins-1 hour Day 1 Cisplatin 25mg/m2 IV over 4 hours Day 1 Cisplatin 25mg/m2 IV over 4 hours Day 1 Cisplatin 25mg/m2 IV over 4 hours Day 1 Post hydrations Day 1

OMB – MTX 1gram (CTIS: 62) Vincristine 1mg/m2 (max 2mg) IV in minibag over 10mins Day 1 Methotrexate 500mg/m2 IV over 12 hours Day 1 Methotrexate 500mg/m2 IV over 12 hours Day 1 Hydrocortisone 100mg IV 30-60 minutes before bleomycin Day 2 Chlorphenamine 10mg IV 30-60 minutes before bleomycin Day 2 Paracetamol 1gram oral, 30-60 minutes before bleomycin Day 2 Bleomycin 15,000iu IV over 12 hours Day 2 Bleomycin 15,000iu IV over 12 hours Day 2

Folinic acid 30mg IV bolus every 6 hours to a total of 12 doses, starting 32 hours after start of methotrexate Intrathecal Methotrexate (CTIS: 782)

Given with EP in EP/OMB-CNS regimen Methotrexate 12.5mg intrathecal dose Folinic acid 7.5mg oral given at 24 and 48 hours post methotrexate

Where folinic acid rescue is prescribed for both intrathecal and IV methotrexate – omit rescue doses for intrathecal methotrexate. Interval between cycles: EP 150/75 alternates weekly with OMB-MTX 1gram if CNS

disease. Intrathecal methotrexate given with EP 150/75. Alternating chemo every week Number of cycles: 8 cycles (ie. EP-OMB x 4) or to normalisation of markers plus 2

cycles. Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA (repeat prior

to cycle 3); Sperm storage if time permits;


Respiratory function tests (and repeat prior to cycle 3) CT TAP; MRI brain. Aim to avoid routine antiemetic steroids.

Test to ok/confirm each cycle of chemo: FBC, U&Es, Mg, LFTs. Repeat EDTA if rising creatinine

Supportive drugs: Antiemetics below as per NWLCN guidelines or as per local policy

EP: Very high risk antiemetics OMB: High risk antiemetics



Additional information: Dose Modifications: Discuss with Consultant Reference: Cancer 1986;57(11):2108-13. Rustin GJ et al

8. Emergency Treatment Sick Patients EP 100/20 (CTIS: 1day: 64, 2day: 66, 3day: 69, 2day emergency: 1513) Most commonly used as initial treatment in patients with very extensive disease particularly

pulmonary disease. Same Chemotherapy is given on 1,2 or 3 consecutive days. Note: these doses are the same as 1-2-3 days of BEP (but without bleomycin). Etoposide 100mg/m2 IV over 30mins-1 hour Prehydrations Cisplatin 20mg/m2 IV over 2 hours Post hydrations Interval between cycles: Repeat determined by consultant often weekly. Number of cycles: Depends on response, often change regimen once condition

improves. Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA (repeat prior

to cycle 3) CT TAP; MRI brain; Sperm storage if time permits. Aim to avoid routine antiemetic steroids.





Additional information: Dose modifications: Discuss with consultant

Reference: Ann.Oncol. 2004;15(9):1377-99. Rustin GJ et al


9. TIP (CTIS: 1120) Dexamethasone* 20mg Oral 12 hours pre paclitaxel Day 1 Dexamethasone* 20mg Oral 3-6 hours pre paclitaxel Day 1 Ranitidine 50mg IV bolus 30-60mins pre-paclitaxel Day 1 Chlorphenamine 10mg IV bolus 30-60mins pre-paclitaxel Day 1

Paclitaxel 175mg/m2 IV over 3hrs Days 1 Prehydrations Days 1,2,3,4,5 Cisplatin 20mg/m2 IV over 2 hrs Days 1,2,3,4,5 Mesna 340mg/m2 IV over 20 mins Days 1,2,3,4,5 Ifosfamide 1200mg/m2 }IV over 1hr Days 1,2,3,4,5 Mesna (in bag with 1200mg/m2 } Days 1,2,3,4,5 Ifosfamide) Mesna 720mg/m2 IV over 12hrs Days 1,2,3,4,5 Neulasta 6mg SC stat 24 hours after last dose of ifosfamide


Interval between cycles: Repeat every 21 days Number of cycles: Relapsed refractory disease: 3-4 cycles Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA (repeat prior

to cycle 3) CT TAP; MRI brain. Aim to avoid routine antiemetic steroids.


Supportive drugs: High risk antiemetics as per NWLCN guidelines or as per local policy. GCSF support starting day 9 for 5 to 7 days



Additional information: Dose modifications: Table See table below Reference: J. Clin Onc 2000 18(12) 2313-8. Motzer RJ et al J. Clin Onc 2009 2a(15S) abstract el6094. Mardiak J et al BCCA protocol adopted February 2012


Table: TIP Due to curative aim of treatment, dose modifications should be avoided and only made after discussion with and under direction of the consultant in charge. However, where a dose reduction is to be made the following may serve as guidance: Side effect; TIP-GCT Dose Modification (Dr P Savage) Haematology Neutrophils Platelets X109/L x109/L �1.0 and �90

Full dose If counts below these limits, delay and discuss with consultant. Consider GCSF to support subsequent cycles escalated back to full dose

Renal Function (PS/NLCN 2009) �60mls/min

40-59mls/min <40mls/min

Full dose all drugs Ifosfamide 30% dose reduction Redo EDTA. If still below 40mls/min Do not give cisplatin If renal function recovered above 40mls/min restart cisplatin with 25% dose reduction. If renal function recovers further to baseline, full dose cisplatin may be resumed after discussion with consultant.

Hepatic Function (SPC) Ifosfamide SPC Bilirubin >ULN Or Transaminases/ALP >2.5 x ULN

No reduction for cisplatin or paclitaxel Discuss with Consultant. Do not give ifosfamide Discuss with consultant. Do not give ifosfamide

10. PAC-E / PAC/PLAT

Regimen used to determine if GCT is still chemosensitive. High dose therapy with stem cell rescue is considered in chemosensitive patients.

10a. PAC-E (CTIS: 648) (New paclitaxel dose Oct 2005)

Etoposide 150mg/m2 IV over 1 hour Day 1 Dexamethasone* 20mg Oral 12 hours pre paclitaxel Day 1 Dexamethasone* 20mg Oral 3-6 hours pre paclitaxel Day 1 Ranitidine 50mg IV bolus 30-60mins pre-paclitaxel Day 1 Chlorphenamine 10mg IV bolus 30-60mins pre-paclitaxel Day 1

Paclitaxel 135mg/m2 IV over 3 hours Day 1

10b. PAC-PLAT (CTIS: 641) Dexamethasone* 20mg Oral 12 hours pre paclitaxel Day 1 Dexamethasone* 20mg Oral 3-6 hours pre paclitaxel Day 1 Ranitidine 50mg IV bolus 30-60mins pre-paclitaxel Day 1 Chlorphenamine 10mg IV bolus 30-60mins pre-paclitaxel Day 1

Paclitaxel 135mg/m2 IV over 3 hours Day 1 Cisplatin 60mg/m2 IV over 2 hours Day 1 Post hydrations Day 1



Interval between cycles: PAC-E alternates with PAC/PLAT every 14 days ie. PAC-E

repeated every 28 days Number of cycles: Relapsed refractory disease: 2-4 cycles

(PACE-PAC/PLAT) x 2-4 Tests before starting course of chemo: FBC, U&Es, Mg, LFTs , EDTA (repeat prior



Supportive drugs: High risk anti-emetics below as per NWLCN guidelines or as per local policy

PAC-E: High risk anti-emetics PAC-PLAT: Very high risk antiemetics



Additional information: Dose modifications: Table below Reference: Reprod. Med. 2004;49(8):655-61 Osbourne R et al

Table: PAC-E / PAC-PLAT Due to curative aim of treatment, dose modifications should be avoided and only made after discussion with and under directions of the consultant in charge. However, where a dose reduction is to be made the following may serve as guidance: Side effect; PAC-E/PAC-PLAT Dose Modification Haematology Neutrophils Platelets x109/L x109/L �1.0 and �80

Full dose If counts below these limits delay and discuss with consultant.

Renal Function Crcl �50mls/min <50mls/min

Full dose all drugs Consider switching to carboplatin 4AUC Etoposide: 25% dose reduction Paclitaxel: Full dose

Hepatic Function Bilirubin >ULN

Discuss with consultant

11. GCP (Hansen Regimen) (CTIS: 1104) Dexamethasone* 20mg Oral 12 hours pre paclitaxel Day 1 Dexamethasone* 20mg Oral 3-6 hours pre paclitaxel Day 1 Ranitidine 50mg IV bolus 30-60mins pre-paclitaxel Day 1 Chlorphenamine 10mg IV bolus 30-60mins pre-paclitaxel Day 1


Gemcitabine 800mg/m2 IV over 1hr Day 1 and 8 Paclitaxel 175mg/m2 IV over 3hrs Day 1 Carboplatin 5(GFR+25)mg IV over 1hr Day 1 *Dexamethasone premed may be changed to a single dose dexamethasone 20mg IV bolus 30-60minutes pre paclitaxel

Interval between cycles: Repeat every 21 days Number of cycles: Relapsed/refractory ovarian

Germ cell tumours: 2-4 cycles Tests before starting course of chemo: FBC, U&Es, LFTs, EDTA (repeat prior to

cycle 3) CT TAP; MRI brain. Aim to avoid routine antiemetic steroids. Aim to avoid routine antiemetic steroids.

Tests to ok/confirm each cycle of chemo: Day 1; FBC, U&Es, LFTs. Repeat EDTA if rising creatinine

Day 8; FBC, U&Es Supportive drugs; Antiemetics as per NWLCN guidelines or as per local policy

Day 1; High risk antiemetics Day 8; Low risk antiemetics



Additional information: Dose modifications: Table below Reference: Gynecol.Oncol. 2005;96(2):444-51 Du Bois A. et al

Table: GCP Due to curative aim of treatment, dose modifications should be avoided and only made after discussion with and under direction of the consultant in charge. However, where a dose reduction is to be made the following may serve as guidance: Side effect; GCP-GCT Dose Modification Haematology Neutrophils Platelets x109/L x109/L Day 1 �1.0 and �80 <1.0 or <80 Day 8 �1.0 and �80 <1.0 or <80 If Neutrophils <0.5 for 4 days Or Neutropenic sepsis Or Platelets <25 Or Platelets <50 for 5 days

Full dose all drugs. Do not treat below these limits. Delay until recovery. Discuss doses with consultant Full dose gemcitabine Omit day 8 chemo and restart next cycle day 22 as planned } } Gemcitabine: Omit day 1 and 8 } }


Side effect; GCP-GCT Dose Modification Renal Function CrCl

�30mls/min

<30mls/min

Carboplatin dose as Calvert equation. Paclitaxel: Full dose Gemcitabine: Full dose Discuss with consultant

Hepatic Function Bilirubin <27micromol/L 27-50micromol/L >50micromol/L

Discuss any dose modification with consultant Full dose all drugs Gemcitabine: 25% dose reduction Paclitaxel: 25% dose reduction Gemcitabine: 25% dose reduction Paclitaxel: 50% dose reduction

12. VeIP (CTIS: 632) Vinblastine 0.11mg/kg (max 10mg) IV in minibag over 10mins Day 1and 2 Prehydrations Day 1,2,3,4,5 Cisplatin 20mg/m2 IV over 2hrs Day 1,2,3,4,5 Mesna 240mg/m2 IV over 20mins Day 1,2,3,4,5 Ifosfamide 1200mg/m2 } IV over 1 hrs Day 1,2,3,4,5 Mesna (in bag 1200mg/m2 } Day 1,2,3,4,5 with ifosfamide) Mesna 720mg/m2 IV over 12hrs Day 1,2,3,4,5

Interval between cycles: Repeat every 21 days Number of cycles: Relapsed/refractory: 4 cycles Tests before starting course of chemo: FBC, U&Es, Mg, LFTs, EDTA (repeat prior






Additional information: Dose modifications: Table below Reference: Ann Inter Med 1988;109(10):846. Loehrer PJ et al Ann Inter Med 1988;109:540-546. Loehrer PJ et al

Table: VelP Due to curative aim of treatment, dose modifications should be avoided and only made after discussion with and under direction of the consultant in charge. However, where a dose reduction is to be made the following may serve as guidance: Side effect; VeIP-GCT Dose Modification (Source: )


Full dose If below these limits delay until recovered then full dose


Side effect; VeIP-GCT Dose Modification (Source: )

Renal Function (NLCN 2009) �60mls/min <60mls/min

40-59mls/min <40mls/min

Full dose all drugs Cisplatin: consider swapping to carboplatin Ifosfamide 30% dose reduction Do not give. Discuss with consultant

Hepatic Function Bilirubin

<26micromol/L 26-51micromol/L

>51micromol/L

Discuss any dose modifications with consultant Full dose all drugs Vinblastine: 50% dose reduction Ifosfamide: 50% dose reduction Gemcitabine: 25% dose reduction Omit vinblastine

13. Oxaliplatin/Gemcitabine (CTIS: 1700) Request local approval before treatment commences Gemcitabine 1000mg/m2 IV over 30mins Day 1 and 8 Oxaliplatin 130mg/m2 IV over 2 hours Day 1 Interval between cycles: Repeat every 21 days Number of cycles: Relapsed/Refractory disease: 6 cycles Tests before starting course of chemo: FBC, U&Es, LFT, Crcl calculated. Do EDTA if Crcl <50mls/min Tests to ok/confirm each cycle of chemo: Day 1: FCB, U&Es, LFTs, Crcl (calculated) Day 8: FBC, U&Es

Supportive drugs with each cycle: High risk antiemetics as per NWLCN guidelines or as per local policy

Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book)


Additional information: Administration notes:

Oxaliplatin is incompatible with normal saline, therefore, the venous access device and administration sets should be flushed with 5% glucose. Patients should be advised to keep warm as exposure to cold post oxaliplatin infusion may aggravate symptoms of peripheral neuropathy and laryngopharyngeal dysthesia. In the event of laryngopharyngeal symptoms during an oxaliplatin infusion, reassure the patient that the symptoms are likely to resolve. This must not be confused with an allergic response which requires emergency intervention. The patient who suffers from laryngopharyngeal spasm may be re-challenged with oxaliplatin at a slower infusion rate of up to 6 hours. On occasions pain may be experienced in the infusion arm, if so, slow infusion rate to a maximum 6 hours. Consider CVAD if problematic. Hypersensitivity Reactions: Stop infusion and institute appropriate support. Discuss with consultant.

Dose modifications: See table below Reference: J. Clin.Onc 22 No.1 (January) 2004. 108-114


Table: Oxaliplatin/Gemcitabine Side Effects; Oxali/Gem-GCT Dose Modifications Haematology Neutrophils Platelets x 109/L x 109/L Day 1 ≥1.5 and ≥ 75 <1.5 or <75 Day 8 �1.5 and �100 1.0-1.4 or 50-59 <1.0 or <50 If Neutropenic fever or Thrombocytopenia <50x109/L

Full dose Delay until recovered. Discuss dose with consultant. Full dose gemcitabine Discuss with consultant. Consider gemcitabine 25% dose reduction Omit day 8 chemo and restart next cycle of gemcitabine and oxaliplatin on DAY 15. Discuss dose with consultant } Next cycle } Oxaliplatin full dose } Gemcitabine 25% dose reduction

Renal function Crcl �30mls/min

< 30mls/min

Full dose Do not give

Hepatic Function Bilirubin >1.5 x ULN ALT/AST/ALP >3.0 x ULN

Do not give Do not give

Non haematological toxicities including Neurotoxicity; Cold related dysaethesia Parasthesia without pain Parasthesia with pain Parasthesia with functional impairment

Discuss with consultant


Side Effects; Oxali/Gem-GCT Dose Modifications Laryngeal dysaesthesia

Administer oxaliplatin over 6 hours

Allergic reactions to oxaliplatin Approximately 9.1% (SPC) incidence of acute hypersensitivity to oxaliplatin usually after more than 6 cycles have been administered. During administration patient may develop rash, fever, swollen mouth/tongue hyper or hypotension etc. This rarely develops to full blown anaphylaxis even with repeated treatment

Grade 1 and 2 If acute hypersensitivity occurs: • Discontinue infusion • Treat with IV corticosteroids and antihistamine • Re-challenge at consultant’s discretion with: (COIN) Dexamethasone 4mg orally every 6 hours starting 24 hours pre chemo Dexamethasone 8mg IV 30 minutes pre chemo Chlorphenamine 10mg IV bolus dose 30 mins pre chemo Ranitidine 50mg IV bolus dose 30mins pre chemo Continue dexamethasone, chlorphenamine and ranitidine for 24-48 hours after oxaliplatin Grade 3 and 4 Treat for full anaphylaxis. DO NOT GIVE further oxaliplatin

14. Etoposide Oral (CTIS: 1699) Etoposide 50mg/m2 Oral Once daily Day 1 to 21 (etoposide oral is available as 50mg or 100mg capsules) Interval between cycles: Repeat every 28 days (1 week break) Number of cycles: Relapsed/Refractory disease 3 cycles Tests before starting course of chemo: FBC, U&Es, LFTs Weekly FBC for first 8 weeks Tests to ok/confirm each cycle of chemo: FBC, U&Es, LFTs Supportive drugs with each cycle: None Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book)


Additional information: Dose modifications: Reference: J. Clin Onc 13 No.5 (May)1995; 1167-1169 Table: Etoposide Oral Side Effects; Etop Oral-GCT Dose Modification Haematology Neutrophils Platelets x109/L x109/L �1.0 and �80 <1.0 or <80 <0.5 or <50

Full dose Withhold treatment until recovered. Discuss with consultant. Withhold treatment for 1 week/until recovered then restart with 25% dose reduction


15. Escalated Dose EP for Relapsed GCT EP 500/60 1 day (CTIS: 1771 ) Etoposide 500mg/m2 IV over 2 hours Day 1 Prehydrations Day 1 Cisplatin 60mg/m2 IV over 2 hours Day 1 Post hydrations Day 1 Interval between cycles: Repeat every 21 days Number of cycles: For consultant use only

Relapsed/Refractory disease: 4-6 cycles Tests prior to course of chemo: FBC, U&Es, Mg, LFTs; Crcl/EDTA (repeat

prior to cycle 3); CT TAP; MRI brain. Aim to avoid routine antiemetics steroids.


Supportive drugs: Very high antiemetics as per NWLCN guidelines or as per local policy

Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book)

Macmillan drug specific information sheets/information prescription as appropriate

NWLCN Neutropenia DVD Additional information: Dose modifications: Discuss with consultant and see page 7 Reference: Professor M Seckl experience 16. Cisplatin weekly plus oral Etoposide (Van der Burg)

Cisplatin plus oral etoposide (CTIS 1835 Cisp 50wk + Etop) weekly for maximum 6 weeks as below. Patients with a response or stable disease then receive oral etoposide (CTIS: 1699) for up to 3 cycles.

16a. Cisp50 wk + Etop (CTIS: 1835) Pre hydrations Days 1, 8, 15 Sodium Chloride 3% 250mls IV over 3 hours Days 1, 8, 15 Cisplatin 50mg/m2 IV over 3 hours Days 1, 8, 15 Post hydrations Days 1, 8, 15 Etoposide 50mg Oral once a day Days 1 to 15

NB. Sodium chloride 3% and cisplatin to run simultaneously. 3% used to reduce renal complications in weekly cisplatin at this dose (Trial used doses up to cisplatin 70mg/m2) Interval between cycles: Repeat day 29 maximum 2 cycles

Maximum 2 cycles (total 6 cisplatin infusions). Patients with a response or stable disease receive oral etoposide 21 day (CTIS regimen 1699 on page 20)

Number of cycles: For consultant use only Relapsed/Refractory disease Maximum 2 cycles

Tests before starting course of chemo: FBC, U&Es, LFTs, EDTA, Crcl must be �60mls/min.

Tests to Ok/Confirm each dose of chemo: Weekly FBC, U&Es, LFTs, Crcl (calculated) must be above 70mls/min if calculated.

Supportive drugs with each cycle: High risk antiemetics as per NWLCN guidelines or as per local policy


Sodium chloride 3% as above Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book)


NWLCN Neutropenia DVD Additional information:

Administration notes Weigh patient before and after cisplatin infusion or monitor urine output. If weight gain >1.5kg or symptomatic of fluid retention: inform doctor, patient may require diuretics.

Dose modifications: See table Van der Berg Cisp 60wk/Etop Ovarian Cancer NB. Original paper administered cisplatin 70mg/m2 weekly for maximum 6 weeks (2 cycles of above)

Reference: B.J. Cancer 2002 86. 19-25. Van der Burg Weekly cisplatin and daily etoposide is highly effective in platinum pre-treated ovarian cancer.

Table: Cisp 50wk + Etop Side-effect; CISP wkly/Etop- GCT Dose modification (Prof Seckl) Haematology WBC x109/L Platelets x109/L Day 8 (Cisplatin no.2) > 2.5 and >75 <2.5 or <75 Day 15 (Cisplatin no.3) >1.5 and >50 <1.5 or <50 Day 29 (Cisplatin no.4) >3.0 and >100 <3.0 or <100 Day 36 (Cisplatin no.5) >2.5 and >75 <2.5 or <75 Day 43 (Cisplatin no.6) >1.5 and >50 <1.5 or <50

Full dose Delay all drugs until recovery, then full dose. Full dose Omit cisplatin (Etoposide ends day 15 anyway) Full dose Delay all drugs until recovery, then full dose Full dose Delay all drugs until recovery, then full dose Full dose Omit cisplatin (Etoposide ends day 43 anyway)

Renal function Crcl �60ml/min <60ml/min

Full dose Stop cisplatin. Discuss with consultant

Neuropathy > grade 2

Stop cisplatin


16b. Etop–21 day (CTIS: 1699) Follows 2 cycles of Cisp-50 wkly + Etop (CTIS:1853) Etoposide 50mg/m2 Oral once a day Days 1 to 21

(max 100mg) If heavily pretreated use max 50mg/day

Interval between cycles: Repeat day 28 Number of cycles: Relapsed/Refractory GCT Usually up to 3 cycles following

2 cycles of Cisp-50 wkly. Further treatment only under direction of consultant in charge. Maximum 9 cycles

Tests before starting course of chemo: FBC, U&Es, LFTs, Tests to Ok/Confirm each cycle of chemo: Weekly FBC (Day 1,8,15 of each cycle)

Three weekly U&Es, LFTs. Supportive drugs with each cycle: Low risk antiemetics Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book)


NWLCN Neutropenia DVD Additional information: Dose modification: See table Etop 21day below Reference: B.J. Cancer 2002: 86, 19-25

Table: Etop-21 day Side-effect; Etop 21day – GCT

Dose modification (Prof Seckl)

Etoposide 21 Day WBC Platelets x109/L x109/L Day 1 �3.0 and �100 <3.0 or <100 Day 8 �2.0 and �50 <2.0 or <50 Day 15 �2.0 and �50 <2.0 or <50

Continue full dose Delay until recovery then full dose Continue Discontinue etoposide until next cycle Continue Discontinue etoposide until next cycle

GERM CELL TUMOURS Section by: Dr Philip Savage and Professor Michael Seckl Version Control Sheet Version Date Author Status Comment

1.00 24.11.05 Susan Whear Draft 1.01 24.11.05 Susan Whear Replaced Previously approved version 1.02 09.07.09 Susan Whear Replaced Previously approved version 2.00 27.04.10 Susan Whear Draft 2.01 27.04.10 Susan Whear Replaced Previously approved version


2.02 24.06.10 Susan Whear Replaced Previously approved version 3.00 07.11.11 Susan Whear Draft 3.01 26.03.12 Susan Whear Draft 3.02 28.05.12 Susan Whear APPROVED Version control box added. Version approved 4.00 16.09.13 Susan Whear Draft Added T-BEP

Changed VEIP Mesna to reflect actual practice.

4.00 15.10.13 Susan Whear Draft Correct page numbers for tables 4.00 16.10.13 Susan Whear Draft Comments and Corrections from Arwa

Kocache 4.00 17.10.13 Susan Whear Draft Added bleomycin premed to all regimens

Amended Hepatic impairment guidelines to >ULN discuss with consultant All bleomycin days 9 and 16 changed in line with T-BEP to days 8 and 15

4.01 17.10.13 Approved Approved by Dr Philip Savage GCT Lead Clinician

4.02 29.10.13 Susan Whear Approved Removed duplicate pre-med entry for POMB-ACE

germ cell regimens approved v4.02 nwlcn 29oct13.pdf

Documents