Approved Regimen for Gynaecological Cancers in Adult Patients 2012

Transcription

1 Approved Regimen for Gynaecological Cancers in Adult Patients 2012

2 Version Control This is a controlled document please destroy all previous versions on receipt of a new version. Date Approved: June 2012 Review Date: June 2014 Version Date Issued Review Date Brief Summary of Change Owner s Name 1.0 September 2004 April April 2008 June 2009 Original Regimen Updated to include all the new regimen 2.0 June 2009 May 2011 Updated with new regimen 2.1 May 2011 June 2012 Treatment Algorithm added 2.2 June 2012 June 2014 HRG updated and bevacizumab (CDF) added Network Chemotherapy Prescribers Group Network Chemobiological Group Network Chemobiological Group Network Chemotherapy Group Chemotherapy Clinical Expert Group For the latest version of these guidelines please see the NEYHCA (Cancer) website Please press control and click on the link below Signature Sheet Agreement of the NEYHCA (Cancer) Gynaecology Regimen This Regimen has been agreed by Title Name Date Agreed Chair of the Gynaecological CEG Mr Theo Giannopoulos 19 th June 2012 Chair of the Chemotherapy CEG Dr Mohammad Butt 19 th June 2012 The Chemotherapy CEG have agreed this regimen 19 th June 2012 Page 2 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

3 Contents Version Control... 2 Signature Sheet... 2 Contents Gynaecology Treatment Algorithms Treatment Algorithm for Gynaecological Cancers Treatment Algorithm for Cervical Cancers Treatment Algorithm for Endometrial Cancers Treatment Algorithm for Cancer of the Vulva Treatment Algorithm for Ovarian Cancers Treatment Algorithm for Germ Cell of the Ovary Cervical Cancers Cisplatin weekly with radiotherapy Carboplatin and Paclitaxel UK (UCLCTC-BRD/05/22-CERVIX, NCT ) Trial protocol Cisplatin every 3 weeks Carboplatin and Paclitaxel Cisplatin & Topotecan Endometrial Cancer Carboplatin and Paclitaxel Carboplatin single agent Ovarian Cancer Carboplatin and Paclitaxel Carboplatin single agent Paclitaxel single agent Liposomal Doxorubicin (Caelyx) Topotecan (Hycamtin) Etoposide Bevacizumab Plus Chemotherapy Germ Cell of Ovary BEP (3 day regimen) Bleomycin/Etoposide(120mg/m 2 /day)/cisplatin BEP (5 day regimen) Bleomycin/Etoposide(100mg/m2/day)/Cisplatin Cisplatin & Etoposide Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 3

4 1. Gynaecology Treatment Algorithms 1.1 Treatment Algorithm for Gynaecological Cancers Gynaecological Cancers Cervical Endometrial Ovarian Vulval Germ Cell 1.2 Treatment Algorithm for Cervical Cancers Cervical Neo-adjuvant Treatment Adjuvant Treatment (Stages IIA, IIB, III & IV) Advanced / Metastatic Treatment Carboplatin & Paclitaxel as per UK (UCLVTC-BRD/BRD/05/22- NCT ) CERVIX trial protocol Cisplatin with Radiotherapy Cisplatin 3 weekly RT already given Carboplatin / Cisplatin & Paclitaxel Cisplatin & Topotecan Page 4 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

5 1.3 Treatment Algorithm for Endometrial Cancers Adjuvant for High Risk Endometrial Adjuvant Stage 1B (Uterine serous papillary & clear cell histology) Recurrent & Metastatic Carcinosarcoma Carboplatin & Paclitaxel Carboplatin & Paclitaxel or Single agent Carboplatin Carboplatin & Paclitaxel or Single agent Carboplatin Stage IV & recurrent disease 1 st line Carboplatin & Paclitaxel 1 st line Single agent Carboplatin 2 nd line Doxorubicin & Cisplatin 1.4 Treatment Algorithm for Cancer of the Vulva VULVA Neo-adjuvant Treatment Metastatic disease Mitomycin C, 5-Flurouracil with Radiotherapy Cisplatin & 5-Flurouracil Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 5

6 1.5 Treatment Algorithm for Ovarian Cancers Ovarian Stage 1A/B G3, 1C-IV PS 0-1 Stage 1A/B G3, 1C-IV, PS >2 Stage III/IV sub-optimally debulked either at primary or delayed primary (interval) surgery, or when preoperative imaging predicts suboptimal debulking and attempted surgery would be inappropriate 1 st line Carboplatin & Paclitaxel 1 st line Single agent Carboplatin 2 nd line treatment 1 st line Bevacizumab & Chemotherapy Relapse >12 months post platinum Relapse 6-12 months post platinum Relapse <6 months post platinum no taxane Carboplatin & Paclitaxel PS 0-1 Single agent Carboplatin Single agent Paclitaxel (if no prior taxane) Relapse <6 months post platinum prior taxane Liposomal Doxorubicin (Caelyx) 3 rd line treatment Single agent Topotecan Cisplatin & Etoposide (van der burg) Carboplatin & Gemcitabine Single agent Etoposide Page 6 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

7 1.6 Treatment Algorithm for Germ Cell of the Ovary Germ Cell Salvaging Completely resected Incompletely resected Platinum sensitive relapsing 6-8 weeks post platinum Dysgerminoma stage 1B Non-dysgerminoma stage 1A (grade 2/3 or 1 with vascular & lymphatic invasion) and higher Dysgerminoma BEP3 (3 cycles) BEP3 (3 cycles) Poor prognostic BEP3 (3 cycles) Cisplatin & Etoposide (1 3 cycles) BEP5 (3 cycles) Cisplatin & Etoposide (1 3 cycles) Etoposide Ifosphamide & cisplatin (4 cycles) Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 7

8 2. Cervical Cancers 2.1 Cisplatin weekly with radiotherapy HRG Code Type Days HRG OPCS Procurement 1 SB01Z X70.1 Delivery 1 SB--Z X7-- Indication & therapeutic intent For the treatment of adenocarcinoma stage IIa, IIb, II and IV Schedule Day Drug Daily Dose Route Diluent Rate Pre hydration for Cisplatin see cisplatin hydration protocol 2 hours Day 1 Ondansetron 8mg IV bolus Dexamethasone 8mg IV bolus Mannitol 20g IV infusion 100ml Sodium chloride 0.9% Cisplatin 40mg/m 2 IV infusion 1 litre Sodium Chloride 0.9% Post hydration for Cisplatin see cisplatin hydration protocol 30 minutes 1 hour 2 hours Hydration for cisplatin see hydration protocol Cycle Length & Number of Cycles given Given weekly with radiotherapy for 5 weeks Pre-treatment investigations Prior to treatment: Full blood count, Serum creatinine, CA125, Creatinine Clearance Prior to each cycle: Full blood count, Serum creatinine, CA125, Creatinine Clearance Dose Modifications Check serum creatinine before each treatment and use Cockcroft & Gault formula to estimate creatinine clearance. If serum creatinine rises by more than 20% or estimated clearance is less than 50ml/minute consider dosage reduction, do DTPA clearance or change to carboplatin Regimen Cisplatin weekly with radiotherapy continued Page 8 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

9 Side Effect Nausea and vomiting Diarrhoea Peripheral neuropathy Ototoxicity Renal toxicity monitor renal function prior to each dose. Avoid concurrent administration of nephrotoxic drugs where possible Extravasation Cisplatin Exfoliant Neutropenia Emetogenic Potential High Risk - level 4 Supportive medication Consider the use of a 5HT3 according to Trust antiemetic policy Dexamethasone 2mg TDS for 3 days post cisplatin Domperidone 20mg TDS for 5 days post cisplatin Notes Rose et al 1999 N. Engl. J. Med. 340: Keys et al 1999 N. Engl. J. Med. 340: R.P Symonds (personal communication with Dr Dealey) Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 9

10 2.2 Carboplatin and Paclitaxel UK (UCLCTC-BRD/05/22-CERVIX, NCT ) Trial protocol HRG Code Type Days HRG OPCS Procurement 1 SB06Z X71.1 Delivery 1 SB14Z X72.1 Indication & therapeutic intent For the neo-adjuvant treatment of adenocarcinoma stage IVa where bulky disease cannot be encompassed by radiotherapy alone as per UK (UCLCTC-BRD/05/22-CERVIX, NCT ) Trial protocol Page 10 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

11 2.3 Cisplatin every 3 weeks HRG Code Type Days HRG OPCS Procurement 1 SB01Z X70.1 Delivery 1 SB13Z X72.2 Indication & therapeutic intent Advanced Cervical Cancer where radiotherapy has already been given Schedule Day Drug Daily Dose Route Diluent Rate Day 1 Pre hydration see cisplatin hydration protocol Aprepitant 125mg Oral Ondansetron 8mg IV bolus Dexamethasone 8mg IV bolus Mannitol 20g IV infusion Sodium Chloride 0.9% 100ml Cisplatin 100mg/m 2 IV infusion Sodium Chloride 0.9% 1 litre Post hydration see cisplatin hydration protocol 2 hours 1 hour prior to chemotherapy 30 minutes 2 hours Hydration regimens for Cisplatin see hydration protocol Cycle Length & Number of Cycles given Repeat every 21 days for 6 cycles Pre-treatment investigations Prior to treatment: Full blood count, Serum creatinine, CA125, Creatinine Clearance Prior to each cycle: Full blood count, Serum creatinine, CA125, Creatinine Clearance Toxicity and dose modifications ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Delay 1 week or repeat FBC: if WCC < 3.0, ANC 1.0 Platelets < 100 Check serum creatinine before each treatment and use Cockcroft & Gault formula to estimate creatinine clearance. If serum creatinine rises by more than 20% or estimated clearance is less than 50ml/minute consider dosage reduction, do DTPA clearance or change to carboplatin Renal If the creatinine clearance is 50-60ml/minute reduce the cisplatin dose by 25%, 40-50ml/min reduce cisplatin dose by 50%. Omit cisplatin if below 40ml/minute Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 11

12 Neuro-/Ototoxicity Patients with a grade 2 or greater CTC neurotoxicity or new functional deterioration in hearing, new tinnitus or new significant high frequency hearing loss should have Cisplatin discontinued Side Effects Nausea and vomiting Diarrhoea Peripheral neuropathy Ototoxicity Renal toxicity monitor renal function prior to each dose. Avoid concurrent administration of nephrotoxic drugs where possible Extravasation Cisplatin Exfoliant Neutropenia Emetogenic Potential Severe Start at level 4 Supportive medication Aprepitant 80mg daily Days 2 & 3 Dexamethasone 4mg BD orally for 3 days Domperidone 20mg TDS for 5 days Page 12 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

13 2.4 Carboplatin and Paclitaxel HRG Code Type Days HRG OPCS Procurement 1 SB06Z X71.1 Delivery 1 SB14Z X72.1 Indication & therapeutic intent Advanced Cervical Cancer where radiotherapy has already been given Drug Schedule Day Drug Daily Route Diluent Rate Dose Sodium Chloride 0.9% 100ml IV Infusion Fast Running Dexamethasone 20mg Oral 12 and 6 hours before Or chemotherapy 1 Give 30 minutes before chemo Dexamethasone 20mg IV Bolus Ondansetron 8mg IV Bolus Via sodium chloride 0.9% drip Cimetidine Or Ranitidine 300mg 50mg IV Bolus IV Bolus Via sodium chloride 0.9% drip Chlorpheniramine 10mg IV Bolus Via sodium chloride 0.9% drip Paclitaxel 175mg/m 2 IV Infusion Sodium Chloride 0.9% 500ml Carboplatin *See IV Infusion Glucose 5% below 250 or 500ml Sodium Chloride 0.9% Slow Bolus 30 minutes prior to chemo. 3 hours minutes 100ml IV Infusion Fast Running **Carboplatin dose = (Creatinine clearance/gfr in ml/min + 25) x AUC where AUC=6 Cycle Length & Number of Cycles given Repeat every 21 day cycle, 6 cycles Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, LDH, Ca++, Mg++, CXR Prior to each cycle: FBC, U+E, Creatinine, LFT s Toxicity and dose modifications Delay if WCC <3x10 9 /litre or platelets <100x10 9 /litre (ANC < 1.5 for some oncologists) ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 13

14 Renal Adequate renal function (EDTA/creatinine clearance >40ml/minute) If the Cockcroft & Gault calculation clearance alters by >20%, an EDTA clearance should be repeated and modification of the chemotherapy dose may be required Hepatic Transient increases in liver enzymes have been reported with carboplatin. If bilirubin > 1.25 x the normal value consideration should be given to a paclitaxel dose modification Neuropathy If patients experience a grade 2 or worse neuropathy reduce Paclitaxel dose to 135mg/m 2 in subsequent cycles. If neuropathy is progressive after this dose reduction discontinue treatment with Paclitaxel Extravasation Carboplatin - irritant Paclitaxel - vesicant Neutropenia Side Effects Nausea and vomiting Myelosuppression CNS toxicity peripheral neuropathy rare, ototoxicity may occur with carboplatin Renal toxicity Mucositis Alopecia Constipation Myalgia, arthralgia Hypersensitivity despite premedication this may still be seen. In the event of a severe reaction stop the infusion and follow chemotherapy induced anaphylactic guidelines. Severe cardiac conduction abnormalities have been rarely reported following paclitaxel administration Emetogenic Potential Moderate Supportive medication If oral premedication used Dexamethasone 20mg at 12 and 6 hours prior treatment See local antiemetic policy for Dexamethasone and 5HT antagonist usage Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS Notes Dexamethasone premedication may be given either by mouth at a dose of 20mg taken 12 hours and 6 hours before chemotherapy, or a single dose of 20mg may be given by slow IV bolus/short infusion 30 minutes prior to paclitaxel. Paclitaxel injection is incompatible with PVC and should be administered via non-pvc tubing and supplied in a non-pvc bag or glass bottle. It should be infused through a suitable 0.22micron in-line filter. Page 14 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

15 2.5 Cisplatin & Topotecan HRG Code Type Days HRG OPCS Procurement 1 SB04Z X70.4 Delivery 1 SB14Z X72.1 Indication & therapeutic intent For the treatment of advanced (stage IVb) recurrent carcinoma of the cervix where radiotherapy has already been given Criteria Stage IVB recurrent or persistent carcinoma of the uterine cervix who are unsuitable for curative treatment with surgery and/or radiotherapy A performance status of 0 2 For patients who have not already received cisplatin Schedule Day(s) Drug Daily Dose Route Diluent Rate 1, 2, 3 Sodium Chloride 0.9% 100ml Infusion Fast Running Dexamethasone 8mg IV Bolus Via sodium chloride 0.9% drip Ondansetron 8mg IV bolus Via sodium chloride 0.9% drip Topotecan 0.75mg/m 2 IV 100ml Sodium 30 minutes Infusion Chloride 0.9% Pre hydration for Cisplatin see cisplatin hydration protocol 2 hours Day 1 Mannitol 20g IV infusion 100ml Sodium chloride 0.9% Cisplatin 50mg/m 2 IV infusion 1 litre Sodium Chloride 0.9% Post hydration for Cisplatin see cisplatin hydration protocol 30 minutes 1 hour 2 hours **Final concentration of Topotecan should be between 25 and 50 micrograms/ml Cycle Length & Number of Cycles given Repeat every 21 days for 6 cycles or until disease progression Pre-treatment investigations Full Blood Count, U&E, LFT, Estimate renal function prior to treatment using Cockcroft & Toxicity and dose modifications Prior to administration of the first course of topotecan, patients must have a baseline ANC of 1.5 x 10 9 /l, a platelet count of 100 x 10 9 /l and a haemoglobin level of 9 g/dl Topotecan should not be re-administered unless the ANC 1.5. Platelets 100 x 10 9 /l, and the haemoglobin level is more than or equal to 9g/dl ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 15

16 Severe neutropenia for 7 days or more or associated with fever or infection reduce 20%. Reduce as above if platelet count falls below 25 x 10 9 /L Renal (Topotecan) In moderate renal impairment (creatinine clearance 20 39ml/min) dose should be reduced to 0.75mg/m 2 Not recommended in patients with creatinine clearance < 20ml/min as no experience in this group (Cisplatin) Check serum creatinine before each treatment and use Cockcroft & Gault formula to estimate creatinine clearance. If serum creatinine rises by more than 20% or estimated clearance is less than 50ml/minute consider dosage reduction, do DTPA clearance Hepatic A clinical decision if bilirubin > 170µmol/L as a lack of information in patients with severely impaired hepatic function Side Effects Myelosuppression - significant Nausea and vomiting Diarrhoea or constipation Stomatitis Fatigue Alopecia Rash Peripheral neuropathy Ototoxicity Renal toxicity monitor renal function prior to each dose. Avoid concurrent administration of nephrotoxic drugs where possible Extravasation Topotecan Exfoliant Cisplatin - Exfoliant Neutropenia Emetogenic Potential High Risk Level 4 Supportive medication Consider the use of a 5HT3 according to Trust antiemetic policy Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS prn The uses of GCSF can be considered Reference Randomized Phase III Trial of Cisplatin With or Without Topotecan in Carcinoma of the Uterine Cervix: A Gynecologic Oncology Group Study Long H J 3 rd et al. Clin Oncol 2005; 23 (21): NICE TA183 The guidance on Topotecan for the treatment of recurrent and stage IVB cervical cancer 28 th October 2009 Page 16 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

17 3. Endometrial Cancer 3.1 Carboplatin and Paclitaxel HRG Code Type Days HRG OPCS Procurement 1 SB06Z X71.1 Delivery 1 SB14Z X72.1 Indication & therapeutic intent For the adjuvant treatment of High Risk endometrial cancer 1 st Line Stage IV and recurrent disease 1 st Line recurrent or metastatic Carcinosarcoma Drug Administration Schedule Day Drug Daily Dose Sodium Chloride 100ml 0.9% Dexamethasone 20mg Give 30 minutes Or before chemo Dexamethasone 20mg Route Diluent Rate IV Infusion Oral IV Bolus 12 and 6 hours before chemotherapy Ondansetron 8mg IV Bolus Via saline drip Cimetidine Or Ranitidine 300mg 50mg IV Bolus IV Bolus Via saline drip Chlorpheniramine 10mg IV Bolus Via saline drip Fast Running Slow Bolus 30 minutes prior to chemo. 1 Paclitaxel 175mg/m 2 IV Infusion Carboplatin *See IV below Infusion Sodium Chloride 0.9% 500ml Glucose 5% 250 or 500ml 180 minutes minutes Sodium Chloride 0.9% 100ml IV Infusion Fast Running **Carboplatin dose = (Creatinine clearance/gfr in ml/min + 25) x AUC where AUC=6 Cycle Length & Number of Cycles given Repeat every 21 day cycle, 6 cycles Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, LDH, Ca++, Mg++, CXR Prior to each cycle: FBC, U+E, Creatinine, LFT s Toxicity and dose modifications Delay if WCC <3x10 9 /litre or platelets <100x10 9 /litre (ANC < 1.5 for some oncologists) ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 17

18 Renal Adequate renal function (EDTA/creatinine clearance >40ml/minute) If the Cockcroft & Gault calculation clearance alters by >20%, an EDTA clearance should be repeated and modification of the chemotherapy dose may be required Hepatic Transient increases in liver enzymes have been reported with carboplatin. If bilirubin > 1.25 x the normal value consideration should be given to a paclitaxel dose modification Neuropathy If patients experience a grade 2 or worse neuropathy reduce Paclitaxel dose to 135mg/m 2 in subsequent cycles. If neuropathy is progessive after this dose reduction discontinue treatment with Paclitaxel Extravasation Carboplatin - irritant Paclitaxel - vesicant Neutropenia Side Effects Nausea and vomiting Myelosuppression CNS toxicity peripheral neuropathy rare, ototoxicity may occur with carboplatin Renal toxicity Mucositis Alopecia Constipation Myalgia, arthralgia Hypersensitivity despite premedication this may still be seen. In the event of a severe reaction stop the infusion and follow chemotherapy induced anaphylactic guidelines Severe cardiac conduction abnormalities have been rarely reported following paclitaxel administration Emetogenic Potential Moderate Supportive medication If oral premedication used Dexamethasone 20mg at 12 and 6 hours prior treatment See local antiemetic policy for Dexamethasone and 5HT antagonist usage Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS Notes Dexamethasone premedication may be given either by mouth at a dose of 20mg taken 12 hours and 6 hours before chemotherapy, or a single dose of 20mg may be given by slow IV bolus/short infusion 30 minutes prior to paclitaxel. Paclitaxel injection is incompatible with PVC and should be administered via non-pvc tubing and supplied in a non-pvc bag or glass bottle. It should be infused through a suitable 0.22micron in-line filter. Page 18 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

19 3.2 Carboplatin single agent HRG Code Type Days HRG OPCS Procurement 1 SB02Z X70.2 Delivery 1 SB12Z X72.3 Indication & therapeutic intent For the adjuvant treatment of High Risk endometrial cancer 1 st Line Stage IV and recurrent disease For the adjuvant treatment of stage 1B and greater Uterine serous papillary and clear cell histology Drug Administration Schedule Day Drug Daily Dose Route Diluent Rate Sodium Chloride 0.9% 100ml IV Infusion Fast Running Day 1 Ondansetron 8mg IV Bolus Via saline drip Dexamethasone 8mg IV Bolus Carboplatin *See below IV infusion Glucose 5% 250 or 500ml minutes *Carboplatin dose = (Creatinine clearance/gfr in ml/min + 25) x AUC AUC=5 for poor risk AUC=7 for good risk previously untreated Cycle Length & Number of Cycles given Repeat every 28 day x 6 cycles Or Repeat every 3 weeks for 6 cycles AUC 6 Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, LDH,Ca++, Mg++, CXR Prior to each cycle: FBC, U+E, Creatinine, LFT s Toxicity and dose modifications Delay if WCC <3x10 9 /litre or platelets <100x10 9 /litre (ANC < 1.5 for some oncologists) ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Renal If the Cockcroft & Gault calculation clearance alters by >20%, an EDTA clearance should be repeated and modification of the chemotherapy dose may be required. Carboplatin not recommended if creatinine clearance < 20ml/min Hepatic Transient elevation of liver enzymes probably no dose reduction necessary Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 19

20 Extravasation Carboplatin - irritant Neutropenia Side Effects Nausea and vomiting Myelosuppression CNS toxicity peripheral neuropathy rare, ototoxicity may occur with carboplatin Renal toxicity Mucositis Alopecia Constipation Hypersensitivity Emetogenic Potential Moderate Supportive medication See local antiemetic policy for Dexamethasone and 5HT antagonist usage Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS Page 20 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

21 4. Ovarian Cancer 4.1 Carboplatin and Paclitaxel HRG Code Type Days HRG OPCS Procurement 1 SB06Z X71.1 Delivery 1 SB14Z X72.1 Indication & therapeutic intent First line for Ovarian Cancer Stages 1A/B G3, 1C-IV with a PS of nd Line for patients relapsed > 12 months post platinum 2 nd Line for patients relapsed 6-12 months post platinum depending on PS and previous toxicities Drug Administration Schedule Day Drug Daily Dose Route Diluent Rate Sodium Chloride 100ml IV Infusion Fast Running 0.9% Dexamethasone 20mg Oral 12 and 6 hours before Or chemotherapy Give 30 minutes before chemo Dexamethasone 20mg IV Bolus Ondansetron 8mg IV Bolus Via saline drip Slow Bolus 30 minutes prior to chemo. 1 Cimetidine Or Ranitidine 300mg 50mg IV Bolus IV Bolus Via saline drip Chlorpheniramine 10mg IV Bolus Via saline drip Paclitaxel 175mg/m 2 IV Infusion Sodium Chloride 180 minutes 0.9% 500ml Carboplatin *See below IV Infusion Glucose 5% 250 or 500ml minutes Sodium Chloride 100ml IV Infusion Fast Running 0.9% **Carboplatin dose = (Creatinine clearance/gfr in ml/min + 25) x AUC where AUC=6 Cycle Length & Number of Cycles given Repeat every 21 day cycle, 6 cycles Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, LDH, Ca++, Mg++, CXR Prior to each cycle: FBC, U+E, Creatinine, LFT s Toxicity and dose modifications Delay if WCC <3x10 9 /litre or platelets <100x10 9 /litre (ANC < 1.5 for some oncologists) ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 21

22 Renal Adequate renal function (EDTA/creatinine clearance >40ml/minute) If the Cockcroft & Gault calculation clearance alters by >20%, an EDTA clearance should be repeated and modification of the chemotherapy dose may be required Hepatic Transient increases in liver enzymes have been reported with carboplatin. If bilirubin > 1.25 x the normal value consideration should be given to a paclitaxel dose modification Neuropathy If patients experience a grade 2 or worse neuropathy reduce Paclitaxel dose to 135mg/m 2 in subsequent cycles. If neuropathy is progressive after this dose reduction discontinue treatment with Paclitaxel Extravasation Carboplatin - irritant Paclitaxel - vesicant Neutropenia Side Effects Nausea and vomiting Myelosuppression CNS toxicity peripheral neuropathy rare, ototoxicity may occur with carboplatin Renal toxicity Mucositis Alopecia Constipation Myalgia, arthralgia Hypersensitivity despite premedication this may still be seen. In the event of a severe reaction stop the infusion and follow chemotherapy induced anaphylactic guidelines Severe cardiac conduction abnormalities have been rarely reported following paclitaxel administration Emetogenic Potential Moderate Supportive medication If oral premedication used Dexamethasone 20mg at 12 and 6 hours prior treatment See local antiemetic policy for Dexamethasone and 5HT antagonist usage Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS Notes Dexamethasone premedication may be given either by mouth at a dose of 20mg taken 12 hours and 6 hours before chemotherapy, or a single dose of 20mg may be given by slow IV bolus/short infusion 30 minutes prior to paclitaxel. Paclitaxel injection is incompatible with PVC and should be administered via non-pvc tubing and supplied in a non-pvc bag or glass bottle. It should be infused through a suitable 0.22micron in-line filter. Page 22 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

23 4.2 Carboplatin single agent HRG Code Type Days HRG OPCS Procurement 1 SB02Z X70.2 Delivery 1 SB12Z X72.3 Indication & therapeutic intent First line for adjuvant or palliative treatment of ovarian Cancer 2 nd Line for patients relapsed 6 12 months post platinum Drug Administration Schedule Day Drug Daily Dose Route Diluent Rate Sodium Chloride 100ml IV Infusion Fast Running Day 1 0.9% Ondansetron 8mg IV Bolus Via saline drip Dexamethasone 8mg IV Bolus Carboplatin *See below IV infusion Glucose5% 250 or 500ml minutes *Carboplatin dose = (Creatinine clearance/gfr in ml/min + 25) x AUC AUC=5 for poor risk AUC=7 for good risk previously untreated Cycle Length & Number of Cycles given 28 day cycle x 6 cycles Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, LDH,Ca++, Mg++, CXR Prior to each cycle: FBC, U+E, Creatinine, LFT s Toxicity and dose modifications Delay if WCC <3x10 9 /litre or platelets <100x10 9 /litre (ANC < 1.5 for some oncologists) ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Renal If the Cockcroft & Gault calculation clearance alters by >20%, an EDTA clearance should be repeated and modification of the chemotherapy dose may be required. Carboplatin not recommended if creatinine clearance < 20ml/min Hepatic Transient elevation of liver enzymes probably no dose reduction necessary Extravasation Carboplatin - irritant Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 23

24 Neutropenia Side Effects Nausea and vomiting Myelosuppression CNS toxicity peripheral neuropathy rare, ototoxicity may occur with carboplatin Renal toxicity Mucositis Alopecia Constipation Hypersensitivity Emetogenic Potential Moderate Supportive medication See local antiemetic policy for Dexamethasone and 5HT antagonist usage Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS Page 24 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

25 4.3 Paclitaxel single agent HRG Code Type Days HRG OPCS Procurement 1 SB04Z X70.4 Delivery 1 SB14Z X72.1 Indication & therapeutic intent Second line for platinum resistant ovarian cancer if no prior taxane Drug Administration Schedule 1 Day Drug Daily Dose Route Diluent Rate Sodium Chloride 100ml IV Infusion Fast Running 0.9% Dexamethasone 20mg Oral 12 and 6 hours before Or chemotherapy Give 30 minutes before chemo Dexamethasone 20mg IV Bolus Ondansetron 8mg IV Bolus Via saline drip Slow bolus 30 minutes before chemo Cimetidine Or Ranitidine 300mg 50mg IV Bolus IV Bolus Via saline drip Chlorpheniramine 10mg IV Bolus Via saline drip Paclitaxel 175mg/m 2 IV Infusion Sodium Chloride 0.9% 500ml 3 hours Sodium Chloride 100ml IV Infusion Fast Running 0.9% Cycle Length & Number of Cycles given Repeat every 21 day Reassess after 3 cycles continue to 6 cycles if responding Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, LDH,Ca++, Mg++, CXR Prior to each cycle: FBC, U+E, Creatinine, LFT s Toxicity and dose modifications Delay if Neutrophils <1x10 9 /litre (< 1.5 for some oncologists) or platelets <100x10 9 /litre Reduce dose by 20% if neutrophils <0.5 or severe peripheral neuropathy ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Renal No dose reductions necessary Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 25

26 Hepatic If bilirubin > 1.25 x the normal value consideration should be given to a paclitaxel dose modification Extravasation Paclitaxel - vesicant Neutropenia Side Effects Nausea and vomiting Myelosuppression Mucositis Alopecia Constipation Peripheral neuropathy Myalgia, arthralgia Hypersensitivity despite premedication this may still be seen. In the event of a severe reaction stop the infusion and follow chemotherapy induced anaphylactic guidelines. Severe cardiac conduction abnormalities have been rarely reported following Paclitaxel administration Emetogenic Potential Moderate Supportive medication If oral premedication used Dexamethasone 20mg at 12 and 6 hours prior treatment See local antiemetic policy for Dexamethasone and 5HT antagonist usage Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS Notes Dexamethasone premedication may be given either by mouth at a dose of 20mg taken 12 hours and 6 hours before chemotherapy, or a single dose of 20mg may be given by slow IV bolus/short infusion 30 minutes prior to paclitaxel. Paclitaxel injection is incompatible with PVC and should be administered via non-pvc tubing and supplied in a non-pvc bag or glass bottle. It should be infused through a suitable 0.22micron in-line filter. Page 26 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

27 4.4 Liposomal Doxorubicin (Caelyx) HRG Code Type Days HRG OPCS Procurement 1 SB09Z X71.4 Delivery 1 SB12Z X72.3 Indication & therapeutic intent Recurrent Ovarian Cancer - palliative (for second line or subsequent treatment of patients whose disease does not respond to, relapses within 12 months from initial post platinum-based therapy) Schedule Day Drug Daily Dose Route Diluent Rate Day 1 Sodium Chloride 0.9% 100ml IV Infusion Dexamethasone 8mg IV Bolus Via saline drip Ondansetron 8mg IV Bolus Via saline drip Fast Running Liposomal Doxorubicin 40mg/m 2 IV Infusion Glucose 5%* After 1 st course 60 minutes if tolerated * Doses under 90mg should be diluted in 250ml Glucose 5%, 90mg and above in 500ml Glucose 5% (If clinicians chose to use the 50mg/m 2 dose) ** Initial infusion should be given at a rate no greater than 1mg/minute. If no infusion reaction is observed then subsequent infusions can be given over 60 minutes Cycle Length & Number of Cycles given Repeat every 28 days x 6 cycles Pre-treatment investigations Prior to first cycle: FBC, U&E, LFT S, CA 125, Cardiac function Prior to each cycles: FBC, U&E, LFT S, CA 125 Toxicity and dose modifications Delay 1 week or repeat FBC: if ANC< 1.5, Platelets < 75 see table below ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Renal Renal clearance not influenced by renal function if creatinine clearance between mls/min. No data for patients with creatinine clearance below 30mls/min Hepatic First Dose If Bilirubin 20-51µmol/L reduce first dose by 25%, If Bilirubin > 51µmol/L reduce first dose by 50% Second dose If first dose tolerated with no rise in bilirubin or liver enzymes increase the dose for the second cycle by 25% i.e. to the next dose level. Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 27

28 Subsequent doses Subsequent cycles may be given at the full dose if tolerated Liposomal Doxorubicin (Caelyx) can be administered to patients with liver metastases with con current elevation of bilirubin and liver enzymes upto 4 x ULN range Haematological Toxicity Grade Neutrophils Platelets Modification (x 10 9 /L) (x 10 9 /L) Resume treatment with no dose reduction < < 75 Wait until Neutrophils > 1.5 & platelets > 75. Re-dose with no dose reduction < <50 As above 4 < 0.5 < 25 Wait until Neutrophils > 1.5, platelets >75. Decrease dose by 25% or give full dose with GCSF Toxicity gradings are based on National Cancer Institute Common Toxicity Criteria (NCI-CTC) Palmar Plantar Erythrodysesthesia (PPE) Week after prior Caelyx dose Toxicity grade after prior Caelyx dose Re-dose unless patient has experienced a 1 previous Grade 3 or 4 skin toxicity, in which case wait an additional week 2 Stomatitis Week 4 Week 5 Week 6 Wait an additional week Re-dose unless patient has experienced a previous grade 3 or 4 skin toxicity in which case wait an additional week Wait an additional week 3 Wait an additional week Wait an additional week 4 Wait an additional week Wait an additional week Decrease dose by 25%; return to 4 week interval Decrease dose by 25%; return to 4 week interval Withdraw patient Withdraw patient Week after prior dose Toxicity Week 4 Week 5 Week 6 Grade 1 Redose unless patient has experienced a previous Grade 3or 4 stomatitis, in which case wait an Redose unless patient has experienced a previous grade 3 or 4 stomatitis in which case wait an Decrease dose by 25%; return to 4 week interval or withdraw patient per physicians assessment additional week additional week 2 Wait an additional week Wait an additional week Decrease dose by 25%; return to 4 wk interval or withdraw patient per physician s assessment 3 & 4 Wait an additional week Wait an additional week Withdraw patient Page 28 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

29 Side Effects Palmar Plantar Erythrodysesthesia (Hand Foot syndrome). Advise patients re measures to prevent (give out booklet). If occurs give pyridoxine prophylaxis, amend dosing as detailed above Myelosuppression. For dose adjustment see above Alopecia Stomatitis. For dose adjustment see above Infusion associated reactions. Usually only occur with first treatment cycle. Characterised by symptoms including asthma, flushing, urticarial rash, chest pain, fever, hypertension, tachycardia, pruritis, sweating, shortness of breath, facial oedema, chills, back pain, tightness in chest or throat and / or hypotension. Temporarily stopping infusion usually resolves these symptoms Nausea Diarrhoea or constipation Extravasation Liposomal Doxorubicin (Caelyx) - exfoliant Neutropenia Emetogenic Potential Moderate Supportive medication See local antiemetic policy for Dexamethasone & 5HT 3 antagonist use Domperidone 20mg TDS 5 days or Metoclopramide 10 to 20mg QDS prn as per local policy Pyridoxine mg daily may be given for treatment or prophylaxis of palmar plantar erythrodysethesia Notes The licensed dose for Liposomal Doxorubicin (Caelyx) is 50mg/m 2, however, a dose of 40mg/m 2 has found to be as effective but with a lower incidence of PPE. Ensure patients given booklet regarding prevention of PPE in addition to standard chemotherapy information Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 29

30 4.5 Topotecan (Hycamtin) HRG Code Type Days HRG OPCS Procurement 1 SB09Z X71.4 Delivery 1 SB14Z X72.1 Indication & therapeutic intent 3 rd Line for treatment of advanced ovarian cancer in platinum- resistant or -refractory patients - palliative Schedule Day Drug Daily Dose Route Diluent Rate Days 1 to 5 Sodium Chloride 0.9% 100ml Infusion Fast Running Dexamethasone 8mg IV Bolus Via saline drip Topotecan 1mg/m 2 to 1.5mg/ m 2 see below* IV Infusion 50 to 100ml ** Sodium 30 minutes *Topotecan dose ranges from 1.0mg to 1.5mg/m 2 depending on patients tolerance **Final concentration of Topotecan should be between 25 and 50 micrograms/ml Cycle Length & Number of Cycles given Repeat every 21 days x minimum 4 cycles Pre-treatment investigations FBC, U&E, LFT, Estimate renal function prior to treatment using Cockcroft & Gault formula Toxicity and dose modifications For first course delay or repeat FBC: If WCC < 3.00, ANC < 1.5, Platelets < 100 For subsequent courses delay one week or repeat FBC: If WCC < 3.00, ANC < 1.0, Platelets < 100 ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Severe neutropenia for 7 days or more or associated with fever or infection reduce dose to 1.25mg/m 2 if previously on 1.5mg/m 2 (and subsequently 1.0mg/m 2 ). Reduce as above if platelet count falls below 25 x 10 9 /L Renal In moderate renal impairment (creatinine clearance 20 39ml/min) dose should be reduced to 0.75mg/m 2 Not recommended in patients with creatinine clearance < 20ml/min as no experience in this group Hepatic A clinical decision if bilirubin > 170µmol/L as a lack of information in patients with severely impaired hepatic function Page 30 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

31 Side Effects Myelosuppression - significant Nausea and vomiting Diarrhoea or constipation Stomatitis Fatigue Alopecia Rash Extravasation Topotecan Exfoliant Neutropenia Emetogenic Potential Moderate Supportive medication Domperidone 20mg TDS or Metoclopramide tabs 10 to 20mg TDS to QDS prn Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 31

32 4.6 Etoposide HRG Code Type Days HRG OPCS Procurement 1 SB01Z X70.1 Delivery 1 SB11Z X73.1 Indication & therapeutic intent Relapsed Ovarian Cancer Schedule Day Drug Daily Dose Route Days 1 to 7 Etoposide 50mg twice daily Oral Cycle Length & Number of Cycles given Repeat every 21 days Routine Investigations Full blood count, Serum creatinine & CA125 prior to each visit Dose Modifications ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Etoposide monotherapy Delay 1 week until recovery if WCC < 3 and/or platelets < 100 on day 1. Discontinue cycle if WCC < 2 and/or platelets < 50 Renal Measured creatinine clearance Dose >50 ml/minute 100% ml/minute 75% <15 ml/minute further dose reduction should be considered Hepatic Etoposide contraindicated in patients with severe hepatic dysfunction Where renal / hepatic functions are abnormal treatment is at physician discretion Side Effects Myelosuppression Alopecia Nausea and vomiting Diarrhoea / constipation Haemorrhage Fatigue Drowsiness Abdominal pain and diarrhoea Stomatitis Hepatic dysfunction Page 32 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

33 Extravasation Not applicable, oral capsule Neutropenia Emetogenic Potential Moderate Supportive medication Metoclopramide 10 to 20mg TDS to QDS prn or Domperidone 20mg TDS to QDS prn Notes Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 33

34 4.7 Bevacizumab Plus Chemotherapy (Cancer Drug Fund) HRG Code Bevacizumab 7.5mg/kg Type Days HRG OPCS Procurement 1 SB09Z X71.4 Delivery 1 SB12Z X72.3 Indication & therapeutic intent For the 1 st line treatment of advanced (stage III/IV) ovarian cancer (including primary peritoneal & fallopian tube cancer), sub-optimally debulked either at primary or delayed primary (interval) surgery, or when pre-operative imaging predicts sub-optimal debulking and attempted surgery would be inappropriate. To be used in combination with carboplatin/paclitaxel or carboplatin alone. Schedule Day Drug Daily dose Route Diluent Rate 1 *Bevacizumab 7.5mg/kg IV infusion **100ml Sodium Chloride 0.9% Over 90** minutes *Bevacizumab must be given in combination with chemotherapy. (Carboplatin & paclitaxel or single agent carboplatin) Bevacizumab Infusion Rate **First infusion of bevacizumab should be infused over 90 minutes. If this first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60 minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes. ***The concentration of the final bevacizumab solution should be kept within the range of mg/ml. Cycle Length & Number of Cycles given Repeat every 21 day until disease progression or unacceptable toxicity Pre-treatment investigations Prior to start of treatment: FBC, U+Es, LFT s, BP, CrCl (calculated), dipstick for proteinuria, INR. Prior to each cycle: FBC, U+Es, CrCl (calculated) dipstick for proteinuria, Blood pressure Notes on the duration of bevacizumab therapy Bevacizumab must be started in combination with chemotherapy. Bevacizumab is not approved for single agent use or to be continued with subsequent line chemotherapy after disease progression. Interruptions to treatment to allow patient s a break e.g. to recover from side effects should not be for more than 4 to 6 week. Treatment holidays and intermittent treatment patterns are not approved Toxicity & Dose Modification Haematological Toxicity Delay 1 week if WBC <3.0, ANC <1.0 Platelets <100 Bevacizumab dose reduction for adverse events is not recommended (SPC). If indicated, bevacizumab therapy should either be permanently discontinued or temporarily suspended until toxicity resolves. Chemotherapy alone may continue if bevacizumab toxicity/side effects dictate that bevacizumab should be withheld. Page 34 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

35 Renal impairment No studies in patients with renal impairment Hepatic impairment No studies in patients with renal impairment Side Effects Hypertension Fatigue or asthenia Diarrhoea Abdominal pain Nausea and vomiting Proteinuria Headache Infusion-associated symptoms / acute hypersensitivity reactions (anaphylaxis, chills and fever, nausea, vomiting, pain, rigors, headache, asthenia etc.) Less Common Toxicities that may be severe or life-threatening include: Arterial/venous thromboembolism GI perforation, fistulas, wound dehiscence Haemorrhage Cardiac failure Pneumonitis Administration Notes Hypertension is commonly observed, may be dose-related and should be managed with antihypertensives, e.g. calcium channel blockers. Units administering bevacizumab must have facilities available for the treatment of anaphylaxis and resuscitation. May not need to stop treatment for minor hypersensitivity e.g. reactions, flushing, localised rash. Must be stopped for major reactions, e.g. hypotension, dyspnoea, angioedema or generalised urticaria. Paracetamol can be used to treat reactions. Bevacizumab therapy should not be initiated for at least 28 days following major surgery or until the surgical wound is fully healed. If elective surgery is planned, bevacizumab should be withheld and the long half-life considered. Emetogenic Potential Mild to Moderate Extravasation The extravsation risk of bevacizumab is uncertain; however it is probably clinically appropriate to treat this as a non-vesicant drug Neutropenia Reference Roche products limited summary of product characteristics 30 th March 2012 Independent radiologic review of GOG218, a phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian (EOC), primary peritoneal (PPC) or Fallopian tube cancer (FTC). RA Burger et al, ASCO 2011 ICON7: A phase III Gynaecologic Cancer InterGroup (GCIG) trial of adding bevacizumab to standard chemotherapy in women with newly diagnosed epithelial ovarian, primary peritoneal, or fallopian tube cancer Interim analysis on overall survival. G Kristensen et al, ASCO 2011 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 35

36 5. Germ Cell of Ovary 5.1 BEP (3 day regimen) Bleomycin/Etoposide(120mg/m 2 /day)/cisplatin HRG Code Type Days HRG OPCS Procurement 1 SB02Z X70.2 Delivery 1 SB12Z X72.3 Indication & therapeutic intent For completely resected dysgerminoma stage 1B or higher For completely respectable non-dysgerminoma stage 1A (grade 2/3 or grade 1 with vascular and lymphatic invasion) and higher For incomplete resected dysgerminoma BEP3 followed by BE Schedule Day Drug Daily Dose Route Diluent Rate 1 & 2 IV Infusion 1 litre Sodium chloride 0.9% 4 hours 1, 2, 3 Ondansetron 8mg IV Bolus Slow Bolus 1, 2, 3 Dexamethasone 8mg IV Bolus Slow Bolus 1, 2, 3 Etoposide 120mg/m 2 IV Infusion 1 & 2 Mannitol 20g IV Infusion 1 & 2 Cisplatin 50mg/m 2 Magnesium sulphate 10mmol IV Infusion 1 litre Sodium chloride 0.9% 100ml Sodium chloride 0.9% 1 litre Sodium chloride 0.9% 1 & 2 Potassium chloride 20mmol IV Infusion 1 litre Sodium chloride 0.9% 1 & 2 Potassium 20mmol IV 1 litre Sodium chloride Infusion chloride 0.9% 1 & 2 Magnesium 8mmol IV 1 litre Sodium chloride Infusion chloride 0.9% 3, 10, 17 Hydrocortisone 200mg IM in 2ml Water for Injections 3, 10, 17 Bleomycin 30,000units IM* 1.5ml Lignocaine 1% 1 hour 30mins 4 hours 4 hours 4 hours 4 hours Note* Bleomycin may be given as an IV injection in N/Saline whilst an in-patient Hydration for Cisplatin may vary Cycle Length & Number of Cycles given Repeat every 21 days for 3 cycles Page 36 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

37 Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, calculated Creatinine Clearance, Magnesium, Pulmonary function, Audiogram Prior to each cycle: FBC, U+E, Creatinine, LFT s, calculated Creatinine Clearance If serum creatinine rising by >20% or calculated creatinine clearance <50ml/min check DTPA Toxicity and dose modifications Myelosuppression Delay cycle until neutrophils > 1.5 and platelets > 100 ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Renal If creatinine clearance <50ml/min or serum creatinine rising by more than 20% reduce dose of cisplatin or consider changing to Carboplatin Consider reducing doses of Bleomycin and Etoposide if significant renal impairment Hepatic Bleomycin patients with abnormal liver function tend to develop lung dysfunction Etoposide contra-indicated in patients with severe hepatic dysfunction Elderly Patients Bleomycin total dose is dependent on age Age in Years Total Dose (IU) Dose per week (IU) 80 and over 100 x x x x x x 10 3 Under x x 10 3 Extravasation Cisplatin exfoliant Etoposide irritant Bleomycin non vesicant Neutropenia Side Effects Myelosuppression Nausea and vomiting Renal toxicity see above. Monitor for signs such as reduced urine output Peripheral neuropathy. Caused by cisplatin Alopecia Diarrhoea / constipation Pneumonitis Ototoxicity Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 37

38 Emetogenic Potential Day 1 to 3 Moderate Day 10 & 17 Low Supportive medication See local antiemetic policy for Dexamethasone and 5HT 3 antagonist use Metoclopramide tabs 10 to 20mg TDS to QDS prn, or Domperidone 20mg TDS to QDS prn Notes Avoid nephrotoxic drugs such as frusemide or aminoglycosides. Discontinue Bleomycin if pneumonitis or symptomatic skin toxicity occur. Total maximum dose for Bleomycin = 360,000units Page 38 Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012

39 5.2 BEP (5 day regimen) Bleomycin/Etoposide(100mg/m2/day)/Cisplatin HRG Code Type Days HRG OPCS Procurement 1 SB03Z X70.3 Delivery 1 SB12Z X72.3 Indication & therapeutic intent For incomplete resected or completely resected poor prognostic non-dysgerminima Schedule Day Drug Daily Dose Route Diluent Rate 1 to 5 Ondansetron 8mg IV Bolus Slow Bolus Dexamethasone 8mg IV Bolus Slow Bolus Etoposide 100mg/m 2 IV Infusion Mannitol 20g IV Infusion *** Cisplatin 20mg/m 2 IV Infusion 1 litre N/Saline 1 hour 100ml N/Saline 30mins 1 litre N/Saline 4 hours 2, 8, 15 Hydrocortisone 200mg IV Bolus in 2ml Water for Injections 2, 8, 15 Bleomycin 30,000units IM* 1.5ml Lignocaine 1% Note: *** Give with a suitable Cisplatin hydration See Cisplatin hydration protocol * Bleomycin may be given as an IV injection in N/Saline whilst an in-patient Cycle Length & Number of Cycles given Repeat every 21 days for 3 cycles then 1 to 3 cycles Etoposide & Cisplatin Slow Bolus Pre-treatment investigations Prior to start of treatment: FBC, U+E, Creatinine, LFT s, calculated Creatinine Clearance, Magnesium, Pulmonary functions, Audiogram Prior to each cycle: FBC, U+E, Creatinine, LFT s, calculated Creatinine Clearance If serum creatinine rising by >20% or calculated creatinine clearance <50ml/min check DTPA Toxicity and dose modifications Myelosuppression Delay cycle until neutrophils > 1.5 and platelets > 100 ALL DOSE MODIFICATIONS TO BE DISCUSSED WITH ONCOLOGY SPECIALIST Renal If creatinine clearance <50ml/min or serum creatinine rising by more than 20% reduce dose of cisplatin or consider changing to Carboplatin Consider reducing doses of Bleomycin and Etoposide if significant renal impairment Chemotherapy CEG Regimen for Gynaecological Cancers Version 2.2 June 2012 Page 39