ASWCS Haematology Chemotherapy Protocols B10.3 VIDE B10.3.1 Indication Neoadjuvant or adjuvant therapy for Ewings sarcoma / PNET.

This is the induction regimen as detailed in the EuroEwing 99 study protocol; a comprehensive programme for the management of Ewings sarcoma which includes post surgical randomisation. All patients should be considered for eligibility (250+ page protocol available on request). All patients registered receive VIDE induction. Combination chemotherapy is also indicated in good performance patients with inoperable disease. B10.3.2 Pre treatment evaluation Record all clinically assessable disease. Investigations to include: CT scan of chest, abdomen & pelvis. MRI of primary tumour where appropriate. Isotope bone scan. Mandatory ECG and ECHO. Bone marrow aspirates and trephine need to be completed before treatment (as staging). Record WHO performance status, current height, weight and surface area. Baseline blood tests including FBC, U&E & LFT. Formal measurement of creatinine clearance (Cr EDTA) is also required. Creatinine clearance >60 mls/min prior to commencing treatment. Give adequate verbal and written information for patients and relatives concerning patients disease, treatment strategy and side effects/mortality risk. Obtain written consent from patient or guardian. If appropriate, discuss potential risk of infertility/early menopause with patient and relatives. Version 2006.1

ASWCS Haematology Chemotherapy Protocols B10.3.3 Drug Regimen Days 1 Drug Vincristine Dose 1.5 mg/ m Route Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, as per national guidance. IV Bolus IV infusion over 1hr in 1000mls Sodium Chloride 0.9%. IV infusion over 3hrs in 1000mls Sodium Chloride 0.9%. Comments Max dose = 2mg Nurse to remain with patient throughout infusion

1-3 1-3

Doxorubicin Etoposide

20 mg/m 150 mg/m

1-3

Ifosfamide

3 grams/m

See below for Mesna doses

Mesna cover recommended: 1. Initial pre - Ifosfamide bolus = 1 g/m - on day 1 only. 2. 3hr infusion concurrent with Ifosfamide = 3 g/m - on days 1 to 3. 3. 18hr infusion (in 1000ml NaCl 0.9%) post - Ifosfamide = 1.8 g/m - on days 1 to 3. This regimen is severely myelosuppressive and the use of the following prophylaxis is mandatory. 1). Antibiotics - Ciprofloxacin 250mg BD on days 7-14. - Fluconazole 50mg OD on days 7-14. - Cotrimoxazole 480mg dose as per local protocol.(Continuous dosing for duration of chemotherapy). 2). G-CSF injection OD SC on days 7-14 (dose as per local protocol). 3). Irradiated blood products for the duration of chemotherapy (because high dose therapy is an eventual possibility). On Treatment monitoring: 1). Cr EDTA after cycle 3 and cycle 6. B10.3.4 Dose reductions Prior to each course check FBC U and E, Creatinine, LFTs, and fractionated Phosphate Clearance (see document on Ifosfamide Chemotherapy management). Cr EDTA after cycle 3 and cycle 6. Defer therapy for 1 week if neutrophils<1.0 x 109/l or platelets < 100 x 109/l

ASWCS Haematology Chemotherapy Protocols Defer therapy & monitor renal function and discuss with consultant oncologist if there is a significant rise in serum creatinine; even if Cr.Cl. > 60mls/min as Ifosfamide may cause delayed renal impairment. NB: Ifosfamide is contra-indicated if Serum Creatinine > 120umol/L, Bilirubin > 17 umol/L or ALT / Alk. Phos. > 2.5 times the upper limit of normal. GFR = 40-59 give 70% dose. GFR < 40 clinical decision (can switch to Cyclophosphamide 1500mg/m2). B10.3.5 Antiemetics This regimen has severe emetogenic potential - refer to local protocol. B10.3.6 Cycle frequency Given every 21 days to a maximum of 6 cycles B10.3.7 Adverse effects Nausea & vomiting. Myelosuppression including risk of sepsis and thrombocytopenia. Mucositis. Constipation. Alopecia. Acute and/or delayed nephropathy. Encephalopathy. Cardiac toxicity. Haemorrhagic cystitis. Peripheral neuropathy. B10.3.8 References EUROEWING 99 Protocol. Written by: Professor Bass Hassan, Consultant Medical Oncologist, BHOC Additional update for vinca alkaloid administration only 30/01/2009 Update written by Becky Bagnall Pharmacist BHOC Update authorised by Jeremy Braybrooke Chairman ASWCS D+T committee Authorised By: Chairman ASWCS Drugs & Therapeutics Committee Name: Digitally signed by Steve Falk Signature Date:

Steve Falk

DN: cn=Steve Falk, o=ASWCS, ou, email=aswcs@aswcs.nhs. uk, c=GB Date: 2009.02.12 12:50:13 Z