Acute Lymphoblastic Leukaemia

1 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol Acute Lymphoblastic Leukaemia Acute Lymphoblastic Leukaemia and Lymphoblastic Lymphoma UKALL 2011 (<25years) Regimen A induction consolidation Protocol M Interim MX 1 Delayed intensification Day 1-28 Delayed intensification Day 29-49 Maintenance Regimen B induction BFM consolidation Interim MX 1 Protocol M Delayed intensification Day 1-28 Delayed intensification Day 29-49 Maintenance Regimen C induction (low risk) POSCU Level 2 POSCU Level 3 Brighton Vincristine,Pegaspargase, Dexamethasone vincristine vincristine vincristine vincristine Mercaptopurine, mercaptopurine, methotrexate Vincristine, mercaptopurine, MTX, dexamethasone Vincristine, Doxorubicin Dexamethasone, Pegaspargase, dexamethasone dexamethasone dexamethasone dexamethasone dexamethasone cyclophosphamide, cytarabine, mercaptopurine cytarabine Vincristine, mercaptopurine, MTX, dexamethasone dexamethasone Vincristine,Pegaspargase, Dexamethasone Daunorubicin vincristine Cyclophosphamide, cytarabine, Mercaptopurine cytarabine Vincristine, 6 MP, MTX, dexamethasone dexamethasone mercaptopurine, methotrexate Vincristine, Doxorubicin Dexamethasone,pegaspargase, cyclophosphamide, cytarabine, dexamethasone daunorubicin cytarabine and cyclophosphamide dexamethasone dexamethasone daunorubicin cytarabine and cyclophosphamide dexamethasone dexamethasone daunorubicin cytarabine and cyclophosphamide dexamethasone dexamethasone 6MP cytarabine Vincristine, 6 MP, MTX, dexamethasone dexamethasone Vincristine,Pegaspargase, Dexamethasone Daunorubicin vincristine dexamethasone daunorubicin dexamethasone daunorubicin dexamethasone daunorubicin

2 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 augmented BFM consolidation Day 1-28 augmented BFM consolidation Day 29-69 Escalating Capizzi MTX Day 1, 12, 22, 32, 42 Protocol M-A Delayed intensification Day 1-28 Delayed intensification Day 29-49 Maintenance Itrathecal MTX Vincristine, Pegaspargase Cyclophosphamide, cytarabine, Mercaptopurine Cyclophosphamide, cytarabine, Mercaptopurine Vincristine, Pegaspagase Vincristine, Methotrexate, cytarabine cytarabine Pegaspargase vincristine mercaptopurine, methotrexate pegaspargase Vincristine, Doxorubicin Dexamethasone, Pegaspargase, Cyclophosphamide, 6MP, Cytarabine, Vincristine dexamethasone Pegaspargase cytarabine Vincristine, Dexamethasone, 6 MP, MTX Protocol Relapsed Acute Lymphoblastic leukaemia IntReALL 2010 (Phase III) trial - once this is available POSCU Level 1 (low risk) POSCU Level 2 POSCU Level 3 Brighton Relapsed ALL treatment guidelines (NB Clofarabine funded by CDF) Phase 1 Induction - standard and Vincristine, Dexamethasone intermediate risk Mitoxantrone, Pegaspargase or Weeks 1-4 Induction - high risk Weeks 1-4 Phase 2 Erwinia asparaginase Clofarabine, Etoposide Cyclophosphamide, Dexamethasone, Pegaspargase or Erwinia asparaginase

3 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Consolidation - all risks Week 5 Vincristine, Dexamethasone Consolidation - all risks Week 6 Consolidation - standard and intermediate risk MTX, pegaspagase or erwinia asparaginase Week 7 etoposide, cyclophosphamide Consolidation - High risk Week 7 Consolidation - High risk Vincristine, Dexamethasone, Pegaspargase or Erwinia asparaginase, Mitoxantrone Week 8 Vincristine Consolidation - High risk Week 9 Phase 3 Intensification -standard and intermediate risk Vincristine, Dexamethasone, Pegaspargase or Erwinia asparaginase, Erwinia Asparaginase, dexamethasone, cytarabine, vincristine week 9 Intensification - standard and intermediate risk week 10 Erwinia Asparaginase, cytarabine Intensification - standard and intermediate risk week 12 Intensification - high risk week 11 MTX, Erwinia Erwinia Asparaginase, dexamethasone, cytarabine, vincristine Intensification - high risk week 12 Erwinia Asparaginase, cytarabine Intensification - high risk week 14 Phase 4 All risks - FLAD Phase 5 MTX, Erwinia Fludarabine, Cytarabine Daunoxome IM with CNS irradiation all risks week 14 Dexamethasone, 6MP, Vincristine,

4 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 week 17 6MP,MTX week 20 Etoposide, cyclophosphamide, Cytarabine, MTX Tioguanine cytarabine cytarabine Etoposide, cyclophopshamide, week 21 cytarabine cytarabine cytarabine Dexamethasone, 6MP, MTX, week 22 Vincristine week 25 6MP,MTX week 28 week 29 IM no CNS irradiation Etoposide, cyclophosphamide, Cytarabine, MTX Tioguanine cytarabine cytarabine Etoposide, cyclophopshamide, cytarabine cytarabine cytarabine all risks week 14 Dexamethasone, 6MP, Vincristine, week 20 week 21 week 22 week 28 week 29 Phase 6 maintenance Etoposide, cyclophosphamide, Cytarabine, MTX Tioguanine cytarabine cytarabine Etoposide, cyclophopshamide, cytarabine cytarabine cytarabine Dexamethasone, 6MP, MTX, Vincristine Etoposide, cyclophosphamide, Cytarabine, MTX Tioguanine cytarabine cytarabine Etoposide, cyclophopshamide, cytarabine cytarabine cytarabine courses 1-7 vincristine, dexamethasone 6MP MTX course 8 vincristine, dexamethasone 6MP MTX intrathecal Refractory ALL FLAG Fludarabine, Cytarabine FLAG-IDA Fludarabine, Cytarabine Idarubicin Clorafabine - single agent Clofarabine

5 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Clorafabine, Etoposide, Cyclophosphamide Clorafabine, Etoposide, Cyclophosphamide Protocol Ph+ve Acute Lymphoblastic Leukaemia EsPhALL guidelines (imatinib funded by CDF) Phase 1B Induction Day 1-29 Consolidation Block 1 Consolidation block 2 Cyclophosphamide 6MP, imatinib, cytarabine MTX, dexamethasone, vincristine, cyclophosphamide, cytarabine, pegasparagase, imatinib dexamethasone, MTX, vindesine, ifosfamide, Daunorubicin, Pegaspargase, imatinib dexamethasone cytarabine Consolidation block 3 etoposide, pegaspargase, imatinib Imatinib - continuation imatinib Intrathecal therapy UKALL R3 +/- Imatinib for details see under ALL (low risk) POSCU Level 2 POSCU Level 3 Brighton Protocol Acute Myeloid Leukaemia Treatment guidelines for AML and high Risk MDS in Children <16years (exc APL and Downs syndrome) ADE 10+3+5 ADE 8+3+5 Etoposide, Cytarabine, Daunorubicin Etoposide, Cytarabine, Daunorubicin Course 3 CYTARABINE Cytarabine Course 4 CYTARABINE Cytarabine FLAG-IDA Fludarabine, Cytarabine, Idarubicin (low risk) POSCU Level 2 POSCU Level 3 Brighton

6 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 TRIPLE IINTRATHECAL CHEMOTHERAPY Methotrexate, Cytarabine, Hydrocortisone AML 17 trial for young adults >18years (mylotarg funding agreed at RMH as currently no national funding stream) ADE 10+3+5 ADE 10+3+5+ mylotarg DA 3+10+mylotarg ADE 8+3+5 ADE 8+3+5+mylotarg (for CBF patients who didn't receive mylotarg in course 1 ) Etoposide, Cytarabine, Daunorubicin Etoposide, Cytarabine, Daunorubicin, Gemtuzumab Ozogamicin Cytarabine, Daunorubicin, Gemtuzumab Ozogamicin Etoposide, Cytarabine, Daunorubicin Etoposide, Cytarabine, Daunorubicin, Gemtuzumab Ozogamicin Course 3 CYTARABINE Cytarabine Course 4 CYTARABINE Cytarabine FLAG-IDA Fludarabine, Cytarabine, Idarubicin CLOFARABINE and DAUNORUBICIN Clofarabine, Daunorubicin TRIPLE IINTRATHECAL CHEMOTHERAPY Methotrexate, Cytarabine, Hydrocortisone Acute Myeloid Leukaemia - Relapsed (based on guidelines from Brenda Gibson 2010) FLA Cytarabine, Fludarabine FLAG-X Cytarabine, Fludarabine, DaunoXome FLA-IDA Fludarabine, Cytarabine Idarubicin CYTARABINE ETOPOSIDE BFM schedule Cytarabine, Etoposide HIDAC Cytarabine Cytarabine, methotrexate, Intrathecal Triple hydrocortisone

7 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Refractory Acute Myeloid Leukaemia - guidelines FLAG Fludarabine, Cytarabine FLAG-IDA Fludarabine, Cytarabine Idarubicin Relapsed and Refractory Flt-3 ITD positive AML (Clofarabine funded by CDF) Clofarabine, Cyclophosphamide, Etoposide Clofarabine, Cyclophosphamide, Etoposide other options for relapsed AML Methotrexate Pegaspargase Methotrexate Pegaspargase L6 tioguanine, cytarabine FLAMSA RIC Amsacrine, Cytarabine Fludarabine, busulfan, cyclophosphamide, ATG AML guidelines for Downs Syndrome ML-DS 2007 AIE Cytarabine Idarubicin Etoposide AI Cytarabine Idarubicin ham Cytarabine Mitoxantrone HA Cytarabine Protocol Acute Pro-myelocytic Leukaemia Acute Promyelocytic Leukaemia - guidelines (low risk) POSCU Level 2 POSCU Level 3 Brighton Induction - standard ATRA, idarubicin induction - high risk ATRA, idarubicin Consolidation 1 ATRA, idarubicin, mitoxantrone consolidation 2 ATRA, idarubicin consolidation 3 ATRA, idarubicin, cytarabine maintenance cycle 1 6MP, MTX maintenance cycle 2 ATRA, 6MP, MTX

8 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 intrathecal therapy Acute Promyelocytic Leukaemia (relapsed) - guidelines (mylotarg needs IFR approval) ATO arsenic trioxide ATRA tretinoin GO gemtuzumab ozogamicin Acute Promyelocytic Leukaemia (CNS relapsed) - guidelines induction consolidation 3rd line gemtuzumab ozogamicin, cytarabine, tretinoin, gemtuzumab ozogamicin, cytarabine, tretinoin, FLAG-IDA Fludarabine, Cytarabine Idarubicin FLAG-DaunoXome Cytarabine, Fludarabine, DaunoXome Protocol Chronic Myeloid Leukaemia Ph +ve Chronic Myeloid Leukaemia - guidelines (imatinib funded by NICE) Imatinib Imatinib Hydroxycarbamide Hydroxycarbamide Dasatinib ALL induction- see UKALL 2011 FLAG See ALL Juvenile Myelomonocytic Leukaemia (JMML) - guidelines Cytarabine, Etoposide 6MP, tretinoin 2nd line use AML guidelines (low risk) POSCU Level 2 POSCU Level 3 Brighton

9 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol B-cell Non Hodgkin s Lymphoma (low risk) POSCU Level 2 POSCU Level 3 Brighton High Risk patients Intergroup Rituximab trial B-NHL CCLG guidelines - 1st line Group A Cyclophosphamide, Doxorubicin, COPAD Vincristine, Prednisolone Group B Cyclophosphamide, Prednisolone, COP COPADM 1+2 CYM 1+2 Group C COP COPADM 1 COPADM 2 Vincristine Cyclophosphamide, Prednisolone, Vincristine, Doxorubicin, Methotrexate Cytarabine, methotrexate Cyclophosphamide, Prednisolone, Vincristine Cyclophosphamide, Prednisolone, Vincristine, Doxorubicin, Methotrexate Cyclophosphamide, Prednisolone, Vincristine, Doxorubicin, methotrexate CYVE 1+2 Cytarabine, Etoposide HD-MTX Maintenance C1 Methotrexate vincristine,prednisolone, methotrexate, cyclophosphamide, doxorubicin Maintenance C 2+4 cytarabine, etoposide vincristine, prednisolone, Maintenance C3 cyclophosphamide, doxorubicin Rituximab Rituximab Intrathecal Treatment MTX and HYD Methotrexate, hydrocortisone CYT and HYD Cytarabine, hydrocortisone Triple Methotrexate, hydrocortisone,

10 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 cytarabine B-NHL 2nd Line - guidelines CYVE Cytarabine, Etoposide ICE Ifosfamide, Cytarabine, Etoposide Rituximab rituximab carmustine,melphalan, etoposide, BEAM cytarabine RMH Primary Mediastinal Large Cell NHL see inter B-NHL trial guidelines R-EPOCH Lymphoproliferative disease Rituximab, prednisolone, Etoposide, Doxorubicin, Vincristine Cyclophosphamide RMH Rituximab Rituximab R-COP Rituximab, Cyclophosphamide, Vincristine, Doxorubicin see also see B-NHL guidelines- modified for according to organ damage Protocol Acute Lymphoblastic Lymphoma UKALL 2011 please refer to ALL section Lymphoblastic lymphomas - Relapsed/Refractory 2nd line please refer to UKALL R3 protocol under ALL relapsed section Lymphoblastic lymphomas - Relapsed/Refractory 3rd line (Nelarabine funding via CDF) FLAG Fludarabine, Cytarabine, GCSF FLAG - IDA Nelarabine, Cyclophosphamide, Etoposide Fludarabine, Cytarabine, GCSF, Idarubicin Nelarabine, Cyclophosphamide, Etoposide (low risk) POSCU Level 2 POSCU Level 3 Brighton

11 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol Anaplastic Large Cell Lymphoma Anaplastic Large Cell Lymphoma - ALCL CCLG guidelines Pre-course P Course AM Course A Course BM Course B Intrathecal cyclophosphamide, dexamethasone, Methotrexate, ifosfamide, cytarabine, etoposide dexamethasone, ifosfamide, methotrexate, cytarabine, etoposide Methotrexate, Dexamethasone, Cyclophosphamide, doxorubicin Methotrexate, Dexamethasone, Cyclophosphamide, doxorubicin Methotrexate, Cytarabine, hydrocortisone Anaplastic Large Cell lymphomas - relapsed guidelines CC ICM ICI dexamethasone, (low risk) POSCU Level 2 POSCU Level 3 Brighton vindesine,cytarabine, etoposide, mitoxantrone, carboplatin, ifosfamide, Idarubicin, carboplatin, ifosfamide, Lomustine, Vinblastine, CVA Cytarabine V vinblastine BEAM Thio/Eto/Bu/ATG Melphalan, Carmustine, Cytarabine, etoposide RMH Thiotepa, Etoposide, Busulfan, ATG, RMH Anaplastic Large Cell lymphomas - relapsed 3rd line Vinblastine Vinblastine

12 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol Hodgkin s Lymphoma Hodgkin s disease - Euronet protocol OEPA COPP Vincristine etoposide (low risk) POSCU Level 2 POSCU Level 3 Brighton prednisolone, doxorubicin Vincristine Cyclophosphamide, prednisolone, procarbazine, vincristine Vincristine COPDAC vincristine, dacarbazine, cyclophosphamide, prednisolone, Vincristine Hodgkins disease - Relapsed protocol Ifosfamide, etoposide, IEP Prednisolone ABVD EPIC D1-5 Doxorubicin, Vinblastine, Bleomycin, dacarbazine Ifosfamide, etoposide, Prednisolone EPIC D10 Cisplatin Carmustine, Etoposide, BEAM Cytarabine, Melphalan RMH Hodgkin s disease - 3rd line (Brentuximab funding via CDF) GEM-P gemcitabine, cisplatin, +/- dexamethasone Brentuximab Brentuximab Hodgkins disease - 4th line Vinblastine (as per ALCL) Vinblastine Lymphocyte Predominant Hodgkins disease CVP OEPA vinblastine, prednisolone, cyclophosphamide Vincristine, etoposide prednisolone, doxorubicin Vincristine Vincristine

13 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol Neuroblastoma Localised Unresectable neuroblastoma (CCLG guidelines) (low risk ) POSCU Level 2 POSCU Level 3 Brighton Carbo-Etoposide Carboplatin, Etoposide CADO Cyclophosphamide, Doxorubicin, Vincristine Irinotecan-TMZ Irinotecan, temozolomide Localised Unresectable neuroblastoma - relapsed Cisplatin-Etoposide Cisplatin, etoposide cyclo-topotecan Cyclophosphamide, topotecan High risk Neuroblastoma HR-NBL trial (open to recruitment) Rapid COJEC D0 and 40 Vincristine Carboplatin etoposide Rapid COJEC D10,30,50,70 Vincristine, Cisplatin Rapid COJEC 20,60 Cyclophosphamide Etoposide Cyclophosphamide, Vincristine N7-CAV Doxorubicin N7-PE Cisplatin, etoposide TVD Topotecan, Vincristine Doxorubicin Bu-Mel Busulfan, Melphalan RMH isotretinoin isotretinoin anti GD2 antibody RMH Neuroblastoma - Refractory after HR-NBL and 2nd line therapies TVD Topotecan, Vincristine Doxorubicin Irinotecan-TMZ Irinotecan, temozolomide cyclo-topotecan Cyclophosphamide, topotecan Cyclo-Etoposide oral Cyclophosphamide Etoposide Neuroblastoma - 3rd line Topotecan with mibg Topotecan Opsoclonus myoclonus (OMS/DES 2011) Dexamethasone, Cyclophosphamide Dexamethasone, Cyclophosphamide

14 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol Ewings Sarcoma (low risk ) POSCU Level 2 POSCU Level 3 Brighton Ewings Sarcoma - Euro-Ewings 2012 trial (includes metastatic disease) Vincristine, Ifosfamide, Etoposide, VIDE Doxorubicin VAI Vincristine, Ifosfamide, actinomycin D Vincristine. Actinomycin D VAC Cyclophosphamide Bu-Mel busulfan, melphalan RMH VCD Vincristine, Cyclophosphamide, Doxorubicin VC Vincristine, Cyclophosphamide IE Ifosfamide, Etoposide Ewings sarcoma - relapsed TMZ-IRINO Temozolomide, Irinotecan Protocol Rhabdomyosarcoma EpSSG RMS 2005 trial (includes metastatic disease) IVADO CVADO Ifosfamide, Vincristine, Actinomycin (low risk ) POSCU Level 2 POSCU Level 3 Brighton D, Doxorubicin Cyclophosphamide Vincristine, Actinomycin D, Doxorubicin Cyclophosphamide Vincristine, CVA Actinomycin D, Ifosfamide, Vincristine, Actinomycin IVA D, VA Vincristine, actinomycin D Vincristine Vinorelbine-Cyclo rhabdomyosarcoma - second line therapy

15 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Topo-Cyclo Topotecan, cyclophosphamide Topo-Carbo Topotecan, carboplatin Etop-Carbo Etoposide, Carboplatin Dox- Carbo Doxorubicin, Carboplatin Dox- Cyclo Doxorubicin, Cyclophosphamide rhabdomyosarcoma relapsed (trial currently open) Vincristine, Irinotecan +/- VI(T) Temozolomide Proforma Wilms tumour Wilms tumour WT 2001 trial (closed) (low risk ) POSCU Level 2 POSCU Level 3 Brighton AVD Actinomycin D, Vincristine Doxorubicin AV-1 Actinomycin D, Vincristine AV-2 Actinomycin D, Vincristine V vincristine etop-carb Etoposide, Carboplatin cyclo-dox cyclophospamide, doxorubicin Wilms tumour relapsed - CCLG guidelines Group B - Course 1 cyclophosphamide, etoposide Group B - Course 2 cyclophosphamide, doxorubicin Group C- Course 1 Carboplatin, Etoposide Group C - Course 2 Cyclophosphamide, Etoposide Melphalan-PBSC Melphalan ICE Ifosfamide, Carboplatin, Etoposide Topotecan Topotecan Clear cell Sarcoma of Kidney (CCSK) - see recommendations in WT 2001 Stage I-III AVA Actinomycin D, Doxorubicin, Vincristine Stage I-III V Vincristine Stage IV - see high risk post-op arm of Wilms

16 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Standard risk - SIOPEL 6 Protocol Hepatoblastoma (low risk ) POSCU Level 2 POSCU Level 3 Brighton Cisplatin Cisplatin Hepatoblastoma - High risk (superplado) Carbo/Dox Carboplatin Doxorubicin Cisplatin Cisplatin Hepatoblastoma - Very High risk SIOPEL 4 guidelines Block A1- Day 1 Cisplatin Block A1 - day 8-9 Cisplatin, Doxorubicin Block A1- day 15 Cisplatin Block A2 - day 29 Cisplatin Block A2 - day 36-37 Cisplatin, Doxorubicin Block A2 - day 43 Cisplatin Block A3 - day 57-58 Cisplatin, Doxorubicin Block A3 - day 64 Cisplatin Block B Carboplatin, Doxorubicin Block C Carboplatin, Doxorubicin Hepatocellular Carcinoma - SIOPEL 5 guidelines (Thalidomide funded at RMH by local agreement) Cisplatin- Dox Cisplatin, Doxorubicin Thalidomide- Cyclo Thalidomide, oral cyclophosphamide Hepatoblastoma - relapsed and refractory Irinotecan Irinotecan Docetaxel Docetaxel Hepatoblastoma - relapsed and refractory Irinotecan Irinotecan

17 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol Soft Tissue Sarcomas (low risk ) POSCU Level 2 POSCU Level 3 Brighton EpSSG NRSTS trial (open trial) Ifos-Dox Ifosfamide, Doxorubicin Vin- Cyclo oral Vinorelbine, Cyclophosphamide Vinorelbine oral Vinorelbine Extracranial rhabdoid tumours - EpSSG NRSTS VDCy Vincristine, Doxorubicin, Cyclophosphamide Cy*CE Carboplatin, Cyclophosphamide, Etoposide Aggressive fibromatosis - EpSSG NRSTS vinblastine, methotrexate IVA Ifosfamide Vincristine ActinomycinD VA Vincristine, actinomycin D tamoxifen Tamoxifen Protocol Rare Tumours (low risk ) POSCU Level 2 POSCU Level 3 Brighton Adrenal - ACT guidelines CCLG 1st line Mitotane, Cisplatin, Etoposide 2nd line Mitotane, Gemcitabine, Docetaxel, 5FU Germ cell tumour CCLG guidelines JEB Carboplatin, Etoposide, bleomycin Urology/gynaecology unit guidelines RMH BEP Cisplatin, Etoposide, Bleomycin Germ cell tumour - relapsed CCLG guidelines VEIP Vinblastine, Ifosfamide, Cisplatin, Pac/Cis/ Gem Paclitaxel, Cisplatin, Gemcitabine Naso-pharyngeal Carcinoma (CCLG guidelines) Cisplatin, 5FU,

18 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Langerhans Cell Histiocytosis (LCH III) Group 1: multi-system "Risk" Patients treatment arm A Course 1 prednisolone, vinblastine Course 2 prednisolone, vinblastine Continuation 6MP, prednisolone, vinblastine treatment arm B course 1 prednisolone, vinblastine, MTX course 2 prednisolone, vinblastine, MTX Continuation prednisolone, vinblastine, po MTX Group 2: low "Risk" Patients course 1 prednisolone, vinblastine course 2 prednisolone, vinblastine continuation prednisolone, vinblastine Group 3: "multifocal bone disease" and "special" site" Initial treatment prednisolone, vinblastine Continuation prednisolone, vinblastine Pleuropulmonary blastoma IVADo Ifosfamide, Vincristine, Actinomycin D, Doxorubicin IVA Ifosfamide, Vincristine, Actinomycin D, Pancreatoblastoma (CCLG guidelines) PLADO cisplatin doxorubicin Proforma Palliative Chemotherapy (low risk ) POSCU Level 2 POSCU Level 3 Brighton Relapsed and refractory solid tumours Cyclo- Etoposide Cyclophosphamide, Etoposide 3x3 Cyclophosphamide, Etoposide 21 day Etoposide Etoposide

19 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Protocol Brain Tumours POSCU Level 1 (low risk) POSCU Level 2 POSCU Level 3 Brighton Low grade gliomas SIOP LGG 2004 trial (now closed but used as guideline) Standard Induction VC Vincristine, Carboplatin Standard induction V Vincristine Consolidation V Vincristine Consolidation VC Vincristine, Carboplatin Consolidation Vcyc Vincristine cyclophosphamide Consolidation Vcis Vincristine Cisplatin Vinblastine Vinblastine Low Grade Gliomas - Relapsed Vinblastine TPCV Tioguanine, Procarbazine, Lomustine Vincristine TMZ Temozolomide subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (IFR funding required) Everolimus Everolimus High Grade Gliomas >3years - CCLG + NICE guidelines TMZ Temozolomide TMZ+DXT Temozolomide High Grade Gliomas <3years - SIOP Infant HGG study High Grade Glioma - Relapsed PCV Procarbazine, Lomustine, Vincristine Lomustine single agent (if unable to tolerate PCV) lomustine Oligodendroglioma guidelines PCV Procarbazine, Lomustine, Vincristine > 3 years Standard risk medulloblastoma PNET5 or ACNS0331 (COG) - off study Regimen B' vincristine, cyclophosphamide vincristine (with DXT) Regimen A' Lomustine, Vincristine Cisplatin vincristine vincristine

20 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 < 3 years Standard risk medulloblastoma (Guidelines) modified' headstart 2 Vincristine, Cisplatin, Methotrexate, cyclophosphamide, etoposide <3 years High Risk PNET (medulloblastoma) guidelines modified' headstart 2 Vincristine, Cisplatin, Methotrexate, cyclophosphamide, etoposide high dose MTX at RMH high dose MTX at RMH Carboplatin, Etoposide Thiotepa >3 years High Risk PNET (medulloblastoma) guidelines Vincristine, Carboplatin (with Radiotherapy) Vincristine, Carboplatin vincristine, cyclophosphamide relapsed PNET (Milan protocol) Induction Vinc/MTX Vincristine, Methotrexate high dose MTX at Induction Etopophos Induction Cyclo/Vinc Induction Carbo/Vinc Etoposide Phosphate Vincristine, cyclophosphamide Carboplatin, Vincristine RMH High dosethiotepa etoposide conditioning Thiotepa Etoposide High dosethiotepa conditioning Thiotepa sequential Cyclo- Etoposide orally Cyclophosphamide, Etoposide Other options (IFR/co-payment funding application necessary) Bevacizumab Temozolomide irinotecan Bevacizumab, Temozolomide, irinotecan Depocyte (intrathecal) Pineoblastoma - treat as high risk PNET guidelines Ependymoma ("Baby Brain" guidelines) Course 1 Vincristine, Carboplatin Course 2 Methotrexate high dose MTX at RMH Course 3 Vincristine cyclophosphamide

21 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Course 4 Cisplatin x2 Ependymoma relapsed (thalidomide funded by internal RMH agreement) Etoposide Etoposide Dana-Farber' regimen thalidomide, Cyclophosphamide, Etoposide, Celecoxib Choroid Plexus tumours ICE Ifosfamide, carboplatin, etoposide Choroid Plexus tumours - relapsed/ refractory Temozolomide Temozolomide Intracranial SIOP germ cell tumour (GCT II) PEI Cisplatin, Etoposide, Ifosfamide PEI (High dose) Cisplatin, Etoposide, Ifosfamide Carbo-PEI cycle 1+3 Carboplatin, Etoposide Carbo-PEI cycle 2+4 ifosfamide, etoposide Atypical teratoid rhabdoid tumour (ATRT) <3years modified' headstart 2 Vincristine, Cisplatin, Methotrexate, cyclophosphamide, etoposide high dose MTX at RMH Carbopatin, Etoposide Thiotepa Atypical teratoid rhabdoid tumour (ATRT) >3years - treat as High risk PNET or High risk sarcoma Choroid plexus carcinoma ICE Ifosfamide, carboplatin., etoposide Palliative chemotherapy (thalidomide funded by internal RMH agreement) Dana-Farber' regimen Thalidomide thalidomide, Cyclophosphamide, Etoposide, Celecoxib sequential Cyclo- Etoposide Cyclophosphamide, Etoposide 3x3' oral Cyclophosphamide, Etoposide Etoposide 21 day oral Etoposide Cyclophosphamide 21 day oral Cyclophosphamide

22 Royal Marsden and St Georges NHS Foundation Trusts PTC list of approved chemotherapy regimens 2015 Diagnosis Transplant Conditioning regimens POSCU Level 1 (low risk) POSCU Level 2 POSCU Level 3 Brighton ATG ATG (Rabbit) Cyclo prime Cyclophosphamide Busulfan Busulfan IV Fludarabine, Alemtuzumab, Cyclophosphamide Fludarabine, Busulfan Fludarabine, Melphalan, Alemtuzumab Fludarabine, Cyclophosphamide Etopophos Thiotepa, Etopophos Busulfan po Busulfan, Alemtuzumab, Cyclophosphamide Busulfan, Melphalan Cyclophosphamide Cyclophosphamide, Busulfan fludarabine Hydration post stem cell infusion Busulfan, melphalan, Cyclophosphamide, Alemtuzumab Melphalan-PBSC Melphalan