Antiemetic Guidelines. Guidelines for the Management of Nausea and Vomiting in Adult Patients Receiving Chemotherapy and/or Radiotherapy

Transcription

1 Antiemetic Guidelines Guidelines for the Management of Nausea and Vomiting in Adult Patients Receiving Chemotherapy and/or Radiotherapy For approvals and version control see Document Management Record on page 23 Doc Ref: AngCN-CCG-C31 Page 1 of 23 Approved and published: Dec 2012

2 CONTENTS The AngCN Antiemetic Guidelines... 1 Guidelines for the Management of... 1 Nausea and Vomiting in Adult Patients Receiving Chemotherapy and/or Radiotherapy Introduction Scope Aims Definitions Grading of Nausea and Vomiting Antiemetic Risk Assessment and Protocol Emetogenic Risk of IV and Oral Chemotherapeutic Agents Assessing the Emetogenic Potential of Chemotherapy Regimens Risk Assessment Assessing Patient Risk Factors Antiemetic Categories, Approved Agents and Uses Antiemetic Regimen Selection Anticipatory nausea and vomiting Management of Antiemetic Failure and Escalation Policy Definition of Antiemetic Failure Management of Antiemetic Failure Radiation Induced Nausea and Vomiting Principles of Management Determinants of Emetic Risk ChemoRadiation Guidance Adverse Drug Reactions associated with commonly-used Antiemetics Appendices Action of Antiemetics on Main Receptor Sites References Acknowledgements Evidence of Agreement Page 2 of 23 Approved and published: Dec 2012

3 1 Introduction The following guidelines have been developed for use within the Anglia Cancer Network for adult oncology and haemato-oncology patients receiving chemotherapy and/or radiotherapy. 1.1 Scope The guidelines apply to the use of antiemetics within Trusts delivering appropriate chemotherapy drugs/regimens. GPs should not be requested to prescribe. 1.2 Aims To reduce the risk of emesis and minimise the side effects and complications of antiemetic drugs To ensure appropriate prescribing and administration of antiemetics for patients receiving chemotherapy and/or radiotherapy, as approved through the Anglia Cancer Network Systemic Anti-cancer Therapies group. 1.3 Definitions Acute Nausea and Vomiting (N and V) N and V experienced during the first 24 hour period immediately after chemotherapy administration Delayed N and V N and V that occurs more than 24 hours after chemotherapy and may continue for up to six or seven days after chemotherapy Anticipatory N and V N and V that occurs prior to the beginning of a new cycle of chemotherapy. It is either a learned response following chemotherapy induced N and V on a previous cycle or an anxiety response. It is most common after three to four cycles of chemotherapy with very badly controlled acute or delayed symptoms Breakthrough N and/or V Development of symptoms (nausea or vomiting), despite standard antiemetic therapy, which require treatment with an additional pharmacological agent Refractory N and V Patients who have failed on both standard and rescue medication Page 3 of 23 Approved and published: Dec 2012

4 1.4 Grading of Nausea and Vomiting Grade Nausea Vomiting 5 Death Death 4 Life-threatening consequences Life-threatening consequences 3 Inadequate oral caloric or fluid intake; IV fluids, tube feedings, or TPN indicated 24 hours six episodes in 24 hours; IV fluids, or TPN indicated 24 hours 2 Oral intake decreased without significant weight loss, dehydration or malnutrition; IV fluids indicated <24 hours Two to five episodes in 24 hours; IV fluids indicated <24 hours 1 Loss of appetite without alteration in eating habits One episode in 24 hours Page 4 of 23 Approved and published: Dec 2012

5 2 Antiemetic Risk Assessment and Protocol 2.1 Emetogenic Risk of IV and Oral Chemotherapeutic Agents It should be noted that appropriate prophylaxis can prevent delayed nausea and vomiting, which is harder to treat. Antiemetic treatment should therefore be escalated rapidly to control nausea and vomiting. Antiemetic therapy needs to be tailored to the treatment regimen used, as these have varying emetogenic potential, and also to the individual patient to whom it is being given. Note: A chemotherapy regimen named in the table in section 2.5 does not imply approval to prescribe. It should be ensured that funding approval has been sought and approved before prescribing. 2.2 Assessing the Emetogenic Potential of Chemotherapy Regimens Level Risk Agent 5 Very High Cisplatin > 60mg/m 2 4 High >90% 3 Moderate- High 31-90% 2 Low 10-30% 1 Minimal <10% Carmustine > 250mg/m 2 Cisplatin > 50mg/m 2 Cyclophosphamide > 1500mg/m 2 Dacarbazine Dactinomycin Alemtuzumab Amsacrine Azacitidine Bendamustine Cabazitaxel Carboplatin Carmustine 250mg/ m 2 Cisplatin 50mg/m 2 Clofarabine Cyclophosphamide mg/m 2 Cytarabine >1g/m 2 Daunorubicin Doxorubicin > 60mg/m 2 Bortezomib Capecitabine Cetuximab Cyclophosphamide IV/PO < 750mg/m 2 Cytarabine < 1g/m 2 Docetaxel Doxorubicin < 60mg/m 2 Etoposide Everolimus Fludarabine Abiraterone Bevacizumab Bexarotene Bleomycin Busulfan (low dose) Chlorambucil Cladribine Dasatinib 5-Fluorouracil Gemcitabine Liposomal Doxorubicin Lapatinib Lenalidomide Mercaptopurine Methotrexate mg/m 2 Mifamurtide Mitomycin C Mitoxantrone Erlotinib Gefitinib Hydroxyurea Ipilimumab Melphalan Mesna (IV) Methotrexate < 50mg/m 2 Nilotinib Epirubicin > 90mg/m 2 Ifosphamide 10g/m 2 Mechlorethamide Streptozocin Trabectedin Procarbazine oral Epirubicin 90mg/m 2 Eribulin Imatinib Idarubicin Ifosphamide <10g/m 2 Irinotecan Melphalan (Single high dose) Methotrexate > 250mg/m 2 Oxaliplatin Procarbazine oral Temozolomide Vinorelbine oral Paclitaxel Paclitaxel albumin Pemetrexed Pentostatin Rituximab Romidepsin Sunitinib Tegafur Teniposide Thalidomide Topotecan Trastuzumab Pazopanib Temsirolimus Vemurafenib Vinblastine Vincristine Vinorelbine Vinflunine Page 5 of 23 Approved and published: Dec 2012

6 Note: Drug combinations have an additive emetic effect. If drugs from the same category are combined, the regimen is classified at a higher emetic risk. If drugs are from different categories, the emetic risk is according to the most emetic drug in the combination. 2.3 Risk Assessment Certain risk factors can be used to predict those patients likely to be more susceptible to the emetogenic effects of chemotherapy or radiotherapy: Female gender Young (<30 years old) History of nausea and vomiting (e.g. sickness in pregnancy, motion sickness) Poor control of emesis with prior chemotherapy or radiotherapy Anxiety 2.4 Assessing Patient Risk Factors Risk Factor Action Chemotherapy induced nausea and vomiting (CINV) after previous chemotherapy If level < four add one to level Female gender Young age< 30 Drink Little or no Alcohol If level three or more then add one to level Anxiety History of Motion Sickness High level of anxiety prior to chemotherapy Add Lorazepam 1mg or Levomepromazine mg P.O. one hour before chemotherapy NB Excess alcohol intake reduces emetic risk: Women >14units/week, Men >21units/wk Other Potential Risk Factors: Partial or complete bowel obstruction; Brain metastases; Electrolyte imbalance (hypercalcaemia, hyperglycaemia, hyponatraemia and uraemia); Opiod induced nausea and vomiting. Page 6 of 23 Approved and published: Dec 2012

7 2.5 Antiemetic Categories, Approved Agents and Uses Many chemotherapy regimens for haemato-oncology patients incorporate corticosteroid treatment (commonly with prednisolone or dexamethasone). These patients should NOT receive dexamethasone as part of their antiemetic regimen even if the chemotherapy regimen falls into Category 2, 3 or 4 in section 2.2 (the Emetogenic Risk table). Generally no patient with acute leukaemia should receive dexamethasone as an antiemetic even if the drug/regimen falls into category 2, 3 or 4 (although some of these regimens may include a corticosteroid as part of the anti-cancer treatment). Drug / Regimen Tumour Site Antiemetic level Comments or special instructions A ABCM Haemato-onc 3 AB week only ABCM Haemato-onc 1 CM week only Abiraterone Urology (prostate) 1 ABVD Haemato-onc 4 AC Breast 3 ACE Germ cell 4 ADE (AML 15) Haemato-onc 3 No dexamethasone as antiemetic Alemtuzumab Haemato-onc 3 Amsacrine Haemato-onc 3 Asparaginase Haemato-onc 1 Azacitidine Haemato-onc 3 B BCG intravesical Urology 1 Bendamustine Haemato-onc 3 BEP Germ cell 5 Including three day and five day Bevacizumab Lower GI 1 In combination with fluoropyrimidine based chemotherapy Bexarotene Skin (cutaneous T 1 cell lymphoma) Bleomycin Various 1 Dexamethasone 8mg PO premedication to prevent reactions Bortezomib Haemato-onc 2 Busulfan (low dose) Haemato-onc 1 C Cabazitaxel Urology (prostate) 3 No dexamethasone TTO as antiemetic as regimen includes prednisolone CAP Lung (thymoma) 4 Capecitabine Lower GI 1 Capecitabine / Various 4 Cisplatin Capecitabine / Lower GI / Upper 2 Irinotecan GI Capecitabine / Breast 1 Lapatinib Carboplatin Germ cell / Gynaecology / Breast 3 Includes high dose e.g. AUC7 and AUC10 Page 7 of 23 Approved and published: Dec 2012

8 Carboplatin / Breast 3 Docetaxel Carboplatin / Lung / 3 Etoposide Neuroendocrine Carboplatin / 5-FU Head and neck / 3 Upper GI Carboplatin (weekly with RT) Head and neck 4 Omit post-chemotherapy dexamethasone Carmustine Haemato-onc / CNS 3 ( 250mg/m 2 ) 4 (>250mg/m 2 ) CAV Lung 3 CDT Haemato-onc 1 Cetuximab Lower GI 2 Cetuximab / Irinotecan / Capecitabine Lower GI 2 Cetuximab / Lower GI 2 Irinotecan / 5FU Cetuximab / Lower GI 3 Oxaliplatin / 5FU Chlorambucil Haemato-onc 1 ChlVPP Haemato-onc 1 CHOP Haemato-onc 4 No dexamethasone as antiemetic CIA Gynaecology 4 Cisplatin Dose > Various 5 60mg/m 2 Cisplatin 60mg/m 2 Various 4 Cisplatin (weekly with RT) Cisplatin / Docetaxel / 5FU Cisplatin / Gynaecology / Doxorubicin Head and Neck Cisplatin / Etoposide Gynaecology / Lung / Neuroendocrine Head and Neck / 3 Omit post-chemotherapy Gynaecology dexamethasone Head and Neck 5 Cisplatin weekly / Gynaecology 4 oral etoposide Cisplatin / 5-FU Various 5 All regimens Cisplatin / Gynaecology 3 Topotecan Cladribine Haemato-onc 1 Clofarabine Haemato-onc 3 CMD Haemato-onc 2 No dexamethasone as antiemetic CMF Breast 2 CMV Urology (bladder) 5 C-VAMP Haemato-onc 3 No dexamethasone as antiemetic CVD Neuroendocrine 4 CVP Haemato-onc 3 No dexamethasone as antiemetic Cyclophosphamide - Oral only Various Page 8 of 23 Approved and published: Dec 2012

9 Cyclophosphamide - Various 3 IV doses <1500mg/m 2 Cyclophosphamide - Haemato-onc 4 IV doses >1500mg/m 2 Cyclophosphamide / Breast 3 Docetaxel Cytarabine - IV doses <1000mg/m 2 Haemato-onc 2 No dexamethasone as antiemetic if AML Cytarabine IV doses 1000mg/m 2 Haemato-onc 3 No dexamethasone as antiemetic if AML C-Z-DEX Haemato-onc 3 No dexamethasone as antiemetic D DA (AML 15/16) Haemato-onc 3 No dexamethasone as antiemetic Dacarbazine Melanoma 4 Dactinomycin Gestational 4 trophoblastic tumours Dasatinib Haemato-onc 1 Daunorubicin / Haemato-onc 3 No dexamethasone as antiemetic Clofarabine (AML 16) Daunorubicin Haemato-onc 3 De Gramont Lower GI 1 (standard/modified) Docetaxel Breast / Upper GI 2 Dexamethasone 8mg PO BD for three days starting day before docetaxel + post chemo domperidone Docetaxel Urology (prostate) 2 Given the concurrent use of prednisolone, the recommended premedication regimen is oral dexamethasone 8mg, twelve hours, three hours and one hour before the docetaxel + domperidone Docetaxel / Capecitabine Docetaxel / Carboplatin Breast 2 Dexamethasone 8mg PO BD for three days starting day before docetaxel + domperidone Lung / Gynaecology 3 Dexamethasone 8mg PO BD for three days starting day before docetaxel + ondansetron / domperidone Docetaxel / Cisplatin Lung 4 Dexamethasone 8mg PO BD for three days starting day before docetaxel + ondansetron / domperidone Docetaxel / Gemcitabine Sarcoma / Gynaecology Docetaxel / Upper GI 3 Irinotecan Doxorubicin Various 3 Doxorubicin weekly Breast 2 2 Dexamethasone 8mg PO BD for three days starting day before docetaxel + post chemo domperidone Page 9 of 23 Approved and published: Dec 2012

10 E EC Breast 3 ECarboF Upper 3 GI/Unknown Primary ECarboX Upper GI / 4 Unknown Primary ECE Lung (thymoma) 4 ECF Upper 4 GI/Unknown Primary ECX Upper GI / 4 Unknown Primary EDP + Mitotane Neuroendocrine 3 EMA-CO Gestational 4 EMA weeks only Trophoblastic Tumour EMA-CO Gestational 2 CO weeks only Trophoblastic Tumour EOF Upper GI 3 EOX Upper GI 3 EP Germ cell / Lung 4 Epi-CMF Breast 3 Epirubicin only Epi-CMF Breast 2 CMF only Epirubicin Breast 3 Epirubicin / Gynaecology 3 Carboplatin Epirubicin (weekly) Breast 2 Eribulin Breast 3 Erlotinib Lung 1 ESHAP Haemato-onc 4 No dexamethasone as antiemetic Etoposide - Oral Various 1 only Etoposide - IV only Various 2 (except high dose etoposide for germ cell) Etoposide Germ cell 3 High dose 1.6g/m 2 etoposide EV Lung 2 Everolimus Renal 1 F FAD Haemato-onc 3 No dexamethasone as antiemetic FC (Fludarabine / Haemato-onc 3 Cyclophosphamide) FEC - All epirubicin Breast 3 doses up to 75mg/m 2 FEC 100 Breast 4 FEC-T Breast 4 FLAG-Ida (AML 15) Haemato-onc 3 No dexamethasone as antiemetic Fludarabine - Oral and IV Haemato-onc 1 Page 10 of 23 Approved and published: Dec 2012

11 5-Fluorouracil Various 1 Includes continuous infusional 5- FU, weekly bolus, and 5-FU + RT regimens FMD Haemato-onc 2 No dexamethasone as antiemetic G GCP Germ cell 3 Dexamethasone 20mg IV pre-three weekly paclitaxel (instead of 8mg) plus other antiemetics Gefitinib Lung 1 Gemcitabine Various 2 Gemcitabine / Lung / Breast / 3 Carboplatin Gyanecology Gemcitabine / Various 4 Cisplatin Gemcitabine / Breast / Bladder / 2 Paclitaxel Germ Cell Gem-TIP Germ Cell 5 Dexamethasone 20mg IV pre-three weekly paclitaxel (instead of 8mg) plus other antiemetics Gemtuzumab Haemato-onc 1 Ozogamicin (Mylotarg ) H Hydroxycarbamide Haemato-onc 1 (Hydorxyurea) Hyper-CVAD + Haemato-onc 3 No dexamethasone as antiemetic Rituxumab I Idarubicin Haemato-onc 3 No dexamethasone as antiemetic if AML Ifosfamide Various 3 Ifosfamide / Sarcoma 3 Doxorubicin Imatinib GIST / Haematoonc 1 Interferon alfa Renal 1 Ipilimumab Melanoma 1 IPO Germ Cell 3 Irinotecan Lower GI 3 Irinotecan / 5FU (FOLFIRI) Lower GI 3 Includes De Gramont and weekly bolus 5FU Irinotecan/mitomycin Upper GI 3 C Irinotecan (weekly) Lower GI 2 IVE Haemato-onc 3 L Lapatinib Breast 1 Lenalidomide Haemato-onc 1 Liposomal Gynaecology 2 Doxorubicin Liposomal Gynaecology 3 Doxorubicin / Carboplatin Lomustine CNS 1 Page 11 of 23 Approved and published: Dec 2012

12 M MACE (AML 15) Haemato-onc 2 No dexamethasone as antiemetic Melphalan Haemato-onc 1 Including PO melphalan + prednisolone; IV melphalan + dexamethasone. Mercaptopurine Haemato-onc 1 No dexamethasone as antiemetic if ALL Methotrexate - oral Various 1 and IV doses <300mg/m 2 only. Methotrexate - IV doses > 300mg/m 2 Haemato-onc 3 No dexamethasone as antiemetic if ALL MidAC (AML 15) Haemato-onc 3 No dexamethasone as antiemetic Mifamurtide Sarcoma 3 MiniBEAM Haemato-onc 3 Day one and six only MiniBEAM Haemato-onc 2 Day two five only Mitomycin C - Urology 1 Intravesical only Mitomycin C / Lower GI 2 For Mitomycin C weeks only Capecitabine Mitomycin C/ 5-FU Lower GI 2 All regimens. For Mitomycin C weeks only. Mitoxantrone Various 2 MM Breast 2 MMM Breast 2 MVAC Urology (bladder) 5 MVC Urology 4 MVP Mesothelioma 4 N Nilotinib Haemato-onc 1 O OMB Germ cell 3 Oxaliplatin Lower GI 3 Oxaliplatin / Lower GI 3 Capecitabine (XELOX) Oxaliplatin / 5FU Lower GI 3 Includes De Gramont and weekly bolus 5FU. P Paclitaxel Various 2 Dexamethasone 20mg IV pre three weekly paclitaxel or 8mg IV pre weekly paclitaxel plus other antiemetics Paclitaxel albumin Breast 2 (Abraxane ) Paclitaxel / Carboplatin Gynaecology / Lung 3 Dexamethasone 20mg IV pre three weekly paclitaxel or 8mg IV pre weekly paclitaxel plus other antiemetics Paclitaxel / Cisplatin Urology (bladder) Pazopanib Renal / 1 Hepatobiliary PCV CNS 1 Page 12 of 23 Approved and published: Dec 2012

13 Pemetrexed / Carboplatin Pemetrexed / Cisplatin Lung / Mesothelioma Lung / Mesothelioma 2 Dexamethasone 4mg PO BD for three days starting day before pemetrexed + other antiemetics 4 Dexamethasone 4mg PO BD for three days starting day before pemetrexed + other antiemetics Pentostatin Haemato-onc 1 (Deoxycoformycin) PMB Gynaecology 4 PMitCEBO Haemato-onc 3 MitCE week only. No dexamethasone as antiemetic. PMitCEBO Haemato-onc 1 BO week only POMB Germ cell 4 Procarbazine Haemato-onc 4 R Raltitrexed Lower GI 2 R-CHOP Haemato-onc 3 No dexamethasone as antiemetic R-CVP Haemato-onc 3 No dexamethasone as antiemetic R-ESHAP Haemato-onc 4 No dexamethasone as antiemetic R-FC Haemato-onc 3 Rituximab Haemato-onc 1 R-IVE Haemato-onc 3 R-MiniBEAM Haemato-onc 3 Day one and six only R-MiniBEAM Haemato-onc 2 Day two five only Romidepsin Haemato-onc 3 R-PMitCEBO Haemato-onc 3 MitCE week only. No dexamethasone as antiemetic. R-PMitCEBO Haemato-onc 1 BO week only S Sorafenib Renal / Hepatobiliary Stanford V Haemato-onc 3 Week one, three, five, seven, nine, eleven only. No dexamethasone as antiemetic. Stanford V Haemato-onc 1 Week two, four, six, eight, ten, twelve only Streptozocin / Neuroendocrine 4 Capecitabine Streptozocin / 5FU Neuroendocrine 4 Sunitinib Renal / GIST 1 T Tegafur Lower GI 1 Temozolamide CNS 1 Temsirolimus Renal 1 Thalidomide Haemato-onc 1 Thioguanine Haemato-onc 1 TIP Germ cell 5 Dexamethasone 20mg IV pre-three weekly paclitaxel (instead of 8mg) plus other antiemetics as per section Topotecan (IV) Gynaecology 2 Topotecan (oral) Lung 2 Trabectedin Sarcoma 4 1 Page 13 of 23 Approved and published: Dec 2012

14 Trabectedin / Gynaecology 4 Liposomal Doxorubicin Trastuzumab Breast 1 Trastuzumab / Upper GI 5 Cisplatin / Capecitabine Trastuzumab / Upper GI 5 Cisplatin / 5FU Trastuzumab/ Docetaxel Trastuzumab/ Paclitaxel Breast 2 Dexamethasone 8mg PO BD for three days starting day before docetaxel + metoclopramide as per section Breast 2 Dexamethasone 20mg IV pre-three weekly paclitaxel (instead of 8mg) plus other antiemetics as per section Breast 1 Trastuzumab/ Vinorelbine U UK ALL XI Induction Haemato-onc 3 No dexamethasone as antiemetic Phase 1 UK ALL XI Induction Haemato-onc 3 No dexamethasone as antiemetic Phase two, Day one, 15, 29 UK ALL XI Induction Haemato-onc 2 No dexamethasone as antiemetic Phase two Day eight, 22 UK ALL XI Haemato-onc 3 No dexamethasone as antiemetic Intensification high dose MTX UK ALL XI Haemato-onc 2 No dexamethasone as antiemetic Consolidation Cycle one, two, four UK ALL XI Haemato-onc 3 No dexamethasone as antiemetic Consolidation Cycle three Day one, eight, 15, 22, 29 V VAD Haemato-onc 3 No dexamethasone as antiemetic VAMP Haemato-onc 3 No dexamethasone as antiemetic VAPEC-B - Week Haemato-onc 3 No dexamethasone as antiemetic one and three only. VAPEC-B - Week Haemato-onc 1 No dexamethasone as antiemetic two and four only VeIP Urology 3 Vemurafenib Melanoma 1 Vinblastine Various 1 Vincristine Various 1 Vinflunine Urology (bladder) 1 Vinorelbine Breast / Lung 1 Includes IV/PO vinorelbine Vinorelbine/ Carboplatin Lung 3 Includes IV/PO vinorelbine Page 14 of 23 Approved and published: Dec 2012

15 Vinorelbine/ Lung 4 Includes IV/PO vinorelbine Cisplatin VIP Germ cell 5 Z Z-DEX Haemato-onc 3 No dexamethasone as antiemetic Page 15 of 23 Approved and published: Dec 2012

16 2.6 Antiemetic Regimen Selection The appropriate antiemetic regimen for the Regimen category designated in the table in section 2.5 should be selected as follows: Level Risk Pre-Chemotherapy Post-Chemotherapy 1 <10% No prophylaxis needed Observation or domperidone or metoclopramide 10-20mg QDS PRN 2 Low 10-30% 3 Mod-high 31-90% 4 High >91% IV dexamethasone 8mg ondansetron 8mg IV plus dexamethasone 8mg IV ondansetron 8mg IV plus dexamethasone 8mg IV Domperidone or metoclopramide 10mg-20mg QDS days one to five PRN Oral dexamethasone 4mg BD two to three days +/- Oral ondansetron 8mg BD for two days plus domperidone or metoclopramide 10-20mg QDS prn Oral dexamethasone 4mg BD three to four days plus Oral ondansetron 8mg BD for three to four days plus domperidone or metoclopramide 10-20mg QDS prn NB: If a patient does not have an adequate response to the above regimens then the dose of ondansetron may be escalated to 16mg per dose or aprepitant should be considered according to Trust policy/availability. Where patients meet the following clinical criteria then palonosetron may be substituted for ondansetron: Dysphagia Diabetes (where dexamethasone contraindicated) 5 Highly Emetic or Grade three to four CTC N and V Aprepitant 125mg PO (plus level four antiemetics) 80mg od for two days after chemotherapy (plus level four antiemetics) 2.7 Anticipatory nausea and vomiting Prescribe lorazepam 1-2mg orally/sublingually at least one hour prior to chemotherapy, in addition to standard antiemetics. If severe, consider 1mg night before chemotherapy and 1mg on the morning of chemotherapy. Page 16 of 23 Approved and published: Dec 2012

17 3 Management of Antiemetic Failure and Escalation Policy 3.1 Definition of Antiemetic Failure Antiemetic failure is defined as two or more episodes of vomiting or prolonged/distressing nausea occurring within 24 hours after chemotherapy treatment despite being treated with antiemetics. All patients should be asked about their response to previous antiemetic treatment, where appropriate, and prior antiemetic failure before each course of chemotherapy. Clinicians should ensure that the patient has taken post chemotherapy drugs regularly as prescribed. There are three significant categories: Acute nausea and vomiting which occurs within 24 hours of chemotherapy. Occurs with most cytotoxic agents to some extent Delayed nausea and vomiting which occurs later than 24 hours after chemotherapy Cisplatin, carboplatin, cyclophosphamide and the anthracyclines are known to cause delayed emesis Anticipatory nausea and vomiting which occurs days or hours before chemotherapy 3.2 Management of Antiemetic Failure If there is no nausea or vomiting, continue on existing anti-emetic regimen If breakthrough treatment is required, give an additional agent that is from a different drug class prn, e.g.: Prochlorperazine 5-10mg po every four to six hours or 3-6mg buccally b.d. OR Metoclopramide 10-40mg po/iv every four to six hours OR Lorazepam 0.5-2mg po/iv/sublingual every four to six hours OR Levomepromazine 6.25mg 12.5mg od - tds po/sc (12.5mg po = 6.25mg sc) OR Haloperidol 1-2mg po every four to six hours OR Nabilone 1-2mg po bd OR dexamethasone if not previously given (or extend the course if delayed nausea and vomiting) Consider adding lorazepam before and after chemotherapy for anti-emetic failure within the first 24 hours and for longer if nausea persists once ondansetron course has finished. Do not extend the length of treatment of ondansetron If nausea and vomiting is controlled with breakthrough anti-emetic regimen, then continue the breakthrough medication on a regular basis If nausea and vomiting not controlled with breakthrough medication, move up to a higher level prophylactic anti-emetic regimen Dexamethasone is the most useful agent for delayed nausea and vomiting Dexamethasone schedule for delayed phase can be administered on a reducing dose e.g. 4mg bd for one day, 4mg od for one day 2mg od for two days to minimise dexamethasone side effects Lorazepam causes amnesia and sedation, and is best for anxious patients or for anticipatory nausea and vomiting To ensure absorption in vomiting patients, consider route of administration of anti-emetics e.g. subcutaneous, intravenous, rectal, buccal, sublingual (Do NOT use suppositories in neutropenic patients) Ensure anti-emetics cover the full period of nausea and vomiting Consider addition of antacids or proton pump inhibitors for patients sensitive to dexamethasone Page 17 of 23 Approved and published: Dec 2012

18 Patients should be told to contact the ward if they start vomiting at home. Delayed vomiting may cause acute renal failure due to dehydration exacerbating the nephrotoxicity of chemotherapy If the patient has failed a level four regimen then the following options should be explored: Level Option Pre-Chemotherapy Post-Chemotherapy 4a Maintain dose of Ondansetron 8mg IV, plus Ondansetron and add Dexamethasone 8mg IV additional agents Oral dexamethasone 4mg BD on days one to four, plus Oral Ondansetron 8mg BD for four days post chemo. 4b 4c Escalate dose of Ondansetron Replace Ondansetron with Palonosetron Ondansetron 12mg IV, plus Dexamethasone 8mg IV Replace I.V and oral Ondansetron with Palonosetron I.V. 250 micrograms 4d Add aprepitant 125mg PO prior to chemotherapy 80mg od for two days after chemotherapy 4 Radiation Induced Nausea and Vomiting 4.1 Principles of Management As for chemotherapy-induced nausea and vomiting, the goal of antiemetic therapy is to prevent nausea and vomiting. The risk of radiation induced emesis varies with the treatment administered. 4.2 Determinants of Emetic Risk The determinants of emetic risk in relation to radiotherapy are as follows: The actual treatment field; The dose of radiotherapy administered per fraction; The pattern of fractionation. 4.3 ChemoRadiation For patients receiving chemoradiation schedules, treat with antiemetic therapy according to the highest emetogenic risk based on the chemotherapy regimen or the radiotherapy treatment field. Page 18 of 23 Approved and published: Dec 2012

19 4.4 Guidance Risk Level Minimal Low Irradiated Area Extremities Breast Head and neck Cranium Lower thorax region Pelvis Pre-radiotherapy Rescue with domperidone or ondansetron Prophylactic or rescue ondansetron Prophylactic Prophylactic antiemetics should continue throughout radiation treatment if patient experiences RINV while receiving therapy For patients who experience RINV while receiving rescue therapy only, prophylactic treatment should continue until radiotherapy is complete Patients should receive antiemetic prophylaxis according to the emetogenicity of Cranospinal Moderate Upper abdomen Hemibody irradiation Upper abdomen, abdominalpelvic, mantle, craniospinal irradiation, and cranial radiosurgery Ondasetron (before each fraction for the entire course of radiotherapy) +/- a short course of dexamethasone during fractions 1 to 5 concurrent chemotherapy, unless the emetic risk with the planned radiotherapy is higher High Total body irradiation (TBI) Total nodal irradiation Ondansteron (before each fraction and for at least 24 hours after completion of radiotherapy) plus five day course of dexamethasone during fractions 1 to 5. Page 19 of 23 Approved and published: Dec 2012

20 5 Adverse Drug Reactions associated with commonly-used Antiemetics 5.1 5HT3 receptor antagonists cause constipation and headache, which can exacerbate nausea. Patients need to be advised accordingly, e.g. lactulose to relieve constipation and paracetamol to relieve headache. If constipation is a problem then alternative treatment options are cyclizine 50mg three times a day or domperidone 20mg four times a day. Laxatives may also be prescribed fluid intake should be encouraged if possible. 5.2 Metoclopramide can rarely cause agitation or the development of extra-pyramidal symptoms particularly in the young female patients. These can occur up to 24 hours after a dose and may vary from facial grimacing and dystonic movements to odd feelings in the mouth, restlessness, somnolence and irritability. Bowel transit time may be reduced and some patients experience diarrhoea. 5.3 Domperidone and metoclopromide should not be used when stimulation of the gastric motility could be harmful. 5.4 Avoid in gastro-intestinal haemorrhage, mechanical obstruction or perforation. 5.5 Levomepromazine inhibits cytochrome P-450. Common side effects are somnolence, asthenia, dry mouth, hypotension, photosensitivity and skin reactions. Avoid in patients with liver dysfunction. 5.6 Lorazepam can cause drowsiness and may affect performance of skilled tasks (driving). 5.7 Prochlorperazine may cause drowsiness. A mild leukopenia occurs in up to 30% of patients on prolonged high dosage. Avoid in patients with liver or renal dysfunction, Parkinson's disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostatic hypertrophy. 5.8 Dexamethasone can cause sleep disturbances, hyperactivity and excessive appetite. They also impaired glucose tolerance. Patients may experience perineal discomfort if the drug is given by I/V bolus. This can be avoided by administration via IV infusion. Use with care in patients with diabetes mellitus. 5.9 Cyclizine may cause antimuscarinic side effects such as dryness of the mouth and drowsiness. Children and the elderly are more susceptible to these effects Aprepitant common ADRs include headaches, hiccups and fatigue. When given in combinations with corticosteroids, the SPC suggests that the oral dexamethasone dose is reduced by 50%, methylprednisolone IV dose is reduced by 25% and the oral dose by 50%. NB for practical reasons it is not necessary to halve post chemotherapy dexamethasone doses as per the aprepitant trial data. Page 20 of 23 Approved and published: Dec 2012

21 6 Appendices 6.1 Action of Antiemetics on Main Receptor Sites Drug D2 antagonist H1 antagonist Muscarinic antagonist 5HT2 antagonist 5HT3 antagonist 5HT4 agonist NK1 inhibitor CB1 agonist GABA mimetic Metoclopramide Domperidone Cyclizine Hyoscine Haloperidol Levomepromazine Aprepitant Ondansetron Granisetron Lorazepam Nabilone Prochlorperazine / Pharmacological activity 0=none or insignificant, + = slight, ++ = moderate, +++ = marked Table adapted from Twycross R, Wilcock A, - Palliative Care Formulary Forth Edition (2011) Page 21 of 23 Approved and published: Dec 2012

22 7 References Jordan, K. et al. Oncologist 2007;12: Hesketh P.J Chemotherapy Induced Nausea and Vomiting (Review Article) N England Journal Med 2008; 358: Hesketh et al. Proposal for Classifying the Acute Emetogenicity of Cancer Chemotherapy. J Clin Oncology (1): Guideline update for MASCC and ESMO in the prevention of chemotherapy and radiotherapy induced nausea and vomiting : results of the Perugia consensus conference Annals of Oncology 2010: 21(supplement 5) v 232-v243. Aapro et al. A phase III double blind, randomised trial of Palonosetron compared with ondansetron in preventing chemotherapy induced nausea and vomiting following highly emetogenic chemotherapy Annals of Oncology : Husband A, Worsley A, Nausea and Vomiting pharmacological management Hospital Pharmacist 2007; 14: Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events, Version 4.0. Bethesda, Md: National Cancer Institute, Division of Cancer Treatment and Diagnosis, Navari R M. Pharmacological management of chemotherapy-induced nausea and vomiting. Focus on recent developments. Drugs 2009; 69 (5): National Comprehensive Cancer Network: Antiemesis. NCCN Clinical Practice Guidelines in Oncology v Available at Accessed 29 October Basch et al ASCO guidelines Antiemetics : American Society of Clinical Oncology Clinical Practice Guideline Update Acknowledgements King s Lynn Antiemetic Guideline. Mount Vernon Antiemetic Guideline. Surrey, West Sussex and Hampshire Cancer Network. Guidelines for the Use of Antiemetics with Chemotherapy. June Accessed via Thames Valley Cancer Network. Antiemetic guidelines for the prophylaxis of Chemotherapy and Radiotherapy induced nausea and vomiting in adults (for use by Haematologists and Oncologists). September Accessed via Debbie Morrison Cambridgeshire PCT - Author of the initial working draft of this Guideline. Page 22 of 23 Approved and published: Dec 2012

23 9 Evidence of Agreement Document management Document ratification and history Approved by: Matthew Small (NOPG Chair) and Hugo Ford (SACT Chair) Date approved: 11 Dec 2012 Date placed on electronic library: Dec 2012 Review period: Two years (or earlier in the light of new evidence) Authors: NOGG Chair Document Owner: Anglia Cancer Network, Tel: ; Version number as approved and published: 1 Unique identifier no.: AngCN-CCG-C31 Monitoring the effectiveness of the Process a) Process for Monitoring compliance and Effectiveness - Review of compliance as determined by audit. Any non compliance to be presented by PQ Manager to the AngCN Business Meeting on an annual basis the minutes of this meeting are retained for a minimum of five years. b) Standards/Key Performance Indicators This process forms part of a quality system working to, but not accredited to, International Standard BS EN ISO 9001:2008. The effectiveness of the process will be monitored in accordance with the methods given in the quality manual, AngCN-QM. Equality and Diversity Statement This document complies with the Suffolk PCT Equality and Diversity statement an EqIA assessment is available on request to Anglia Cancer Network PQ Manager, Gibson Centre, Exning Road, Newmarket, CB8 7JG. Disclaimer It is your responsibility to check against the electronic library that this printed out copy is the most recent issue of this document. Page 23 of 23 Approved and published: Dec 2012