West of Scotland Cancer Network Guideline for Managing Chemotherapy Induced Nausea and Vomiting Definitions Acute nausea and vomiting Delayed nausea and vomiting Anticipatory nausea and vomiting Initial 24 hours after chemotherapy > 24 hours after chemotherapy Days to hours prior to chemotherapy Principles of anti-emetic therapy There are 4 categories of emetogenic risk for individual chemotherapy agents, namely high risk, moderate risk, low risk and minimal risk. High risk is further divided into cisplatin based and non-cisplatin based. When patients are receiving combination chemotherapy the anti-emetic regimen for the highest risk agent should be used. For low risk and above if all agents in the combination have the same emetogenic risk, the regimen may be classified as a higher risk. Patient risk factors for CINV should also be considered. Risk factors include; previously uncontrolled nausea and vomiting with chemotherapy, younger age, female, history of travel sickness or anaesthetic sickness, anxiety. Patients who have a history of high alcohol intake seem to be lower risk. If a patient has uncontrolled nausea and vomiting with the first line anti-emetics then the anti-emetic regimen must be reviewed. Optimal emetic control in the acute phase is essential to prevent CINV in the delayed phase. Failure to control CINV in the acute phase is highly predictive for delayed emesis in the delayed phase. Dexamethasone is the most useful agent for delayed CINV. Anticipatory nausea and vomiting is often due to previously uncontrolled nausea and vomiting. Good anti-emetic control from cycle one is the best preventative measure. However in some patients lorazepam (1mg IV pre chemo or 0.5-1mg po night before and morning of chemo) may be beneficial. Anti-emetics should be started at least 30 minutes before the start of chemotherapy (I hour in the case of oral anti-emetics) Oral and IV formulations are equally effective providing the patient is not vomiting and there are no barriers to GI absorption. When prescribing ondansetron for delayed emesis lactulose 10 ml at night should also be prescribed for the duration of ondansetron therapy For refractory patients consider levomepromazine SC 12.5 mg over 24 hours via syringe driver day of and up to 5 days post chemotherapy (with appropriate breakthrough doses as required). Reduce dose to 6.25 mg over 24 hours if excessive drowsiness. Aprepitant is included as a second line option in this guideline for cisplatin based chemotherapy. Use of aprepitant for non-cisplatin based regimens would be subject to case by case approval via local non-formulary request process. WOSCAN CINV V 1.0 Issue Date: September 2010 Review Date: September 2012 Page 1 of 5
Table 1: Classification of chemotherapy drugs by emetogenic risk High risk (Cisplatin based) >90% of patients High risk >90% of patients 30%-90% of patients 10% - 30% of patients Cisplatin Carmustine Cyclophosphamide High dose (1500mg/m2 or above) Dacarbazine Dactinomycin Lomustine (oral) Amsacrine Carboplatin Crisantapase (Asparaginase) Cyclophosphamide (iv and oral) Cytarabine (>1 g/m2) Daunorubicin Doxorubicin (conventional) Epirubicin Etoposide (oral) Cytarabine 1 g/m2 Docetaxel Doxorubicin (liposomal) Etoposide (iv) Gemcitabine Procarbazine (oral) - See individual protocol Melphalan (iv) Mustine Streptozocin Treosulfan (BMT conditioning doses) Idarubicin Ifosfamide Irinotecan Methotrexate High Dose Oxaliplatin Temozolomide(oral) Treosulfan Vinorelbine (oral) Methotrexate (iv) Mitomycin Mitoxantrone Paclitaxel Pemetrexed Topotecan (iv and oral) <10% of patients Alemtuzumab Bevacizumab Bleomycin Bortezomib Fludarabine Fluorouracil Gefitinib (oral) Hydroxycarbamide (oral) Sunitinib (oral) Tegafur with uracil (oral) Temsirolimus Tioguanine (oral) Busulfan Imatinib (oral) Thiotepa Capecitaine (oral) Melphalan (oral) Trastuzumab Cetuximab Mercaptopurine Vinblastine Chlorambucil (oral) Methotrexate (oral) Vincristine Cladribine Nilotinib Vindesine Dasatinib Rituximab Vinorelbine (iv) Erlotinib Sorafenib (oral) WOSCAN CINV V 1.0 Issue Date: September 2010 Review Date: September 2012 Page 2 of 5
Table 2: Recommended first line anti-emetic regimen (note exceptions below) Classification of chemotherapy drugs High risk (cisplatin based and non-cisplatin based) Anti-emetic regimen Dexamethasone 8mg (iv or oral) Ondansetron 8 mg iv or 16mg oral (as 8 mg BD) Dexamethasone 2 mg TDS for 3 days starting day after chemotherapy Domperidone 20 mg QDS for 5 days starting evening of chemotherapy Dexamethasone 8 mg (iv or oral) Ondansetron 8 mg (iv or oral) Dexamethasone 2 mg TDS for 3 days starting day after chemotherapy Domperidone 20 mg TDS for 3-5 days as directed starting evening of chemotherapy. Duration will be dependent on individual patient requirements. Dexamethasone 8 mg (iv or oral) None routinely Consider giving Domperidone 20mg TDS prn with Cycle 1 None routinely Consider giving Domperidone 20mg TDS prn with Cycle 1 Exceptions Where a corticosteroid anti-emetic schedule is specifically defined in the individual protocol eg some sarcoma and BMT regimes where higher doses are used Patients who are receiving corticosteroids as part of their chemotherapy should not receive additional dexamethasone Patients receiving paclitaxel, docetaxel or pemetrexed should receive dexamethasone doses as recommended in individual protocols to minimise hypersensitivity reactions Where the individual chemotherapy protocol states a different anti-emetic regimen e.g oral vinorelbine, minimal risk single agent oral regimens Sarcoma patients should also receive lorazepam 1 mg IV pre chemotherapy where specified in the individual protocols. WOSCAN CINV V 1.0 Issue Date: September 2010 Review Date: September 2012 Page 3 of 5
Table 3: Anti-emetics after failure of first line therapy Classification of chemotherapy drugs High risk (cisplatin based) Second line anti-emetic regimen Dexamethasone 8mg (iv or oral) Aprepitant 125 mg oral 1 hour before chemo Ondansetron 8 mg iv or 16mg oral (as 8 mg BD) Dexamethasone 2 mg TDS for 3 days starting day after chemotherapy Aprepitant 80 mg daily for 2 days starting day after chemotherapy Also consider: Switch domperidone to ondansetron 8 mg BD for 5 days Switch domperidone to cyclizine 50 mg TDS for 5 days Switch domperidone to levomepromazine 6-12mg BD for 5 days High risk (non-cisplatin based) Switch domperidone to ondansetron 8 mg BD for 5 days Switch domperidone to cyclizine 50 mg TDS for 5 days Switch domperidone to levomepromazine 6-12mg BD for 5 days As above addition of dexamethasone post chemo 2mg TID for 3 days starting day after chemotherapy addition of domperidone 20 mg TDS for 3-5 days or ondansetron 8 mg BD for 3-5 days give dexamethasone 8 mg pre-chemo post chemo anti-emetics as above WOSCAN CINV V 1.0 Issue Date: September 2010 Review Date: September 2012 Page 4 of 5
References The recommendations made in these guidelines are based on the following: American Society of Clinical Oncology Guideline for Anti-emetics in Oncology: Update 2006. Journal of Clinical Oncology 2006; 24 (18):2932-2947 Multinational Association of Supportive Care in Cancer: Anti-emetic Guidelines (updated March 2008). Solimando DA. Drug Information Handbook for Oncology. 4 th edition. Lexi-Comp. Summary of Product Characteristics for individual drugs. Expert opinion and current practice. Written By: Reviewed By: Approved By: Issue Date: September 2010 Review Date: September 2012 Version 1.0 Replaces Not Applicable Carla Forte, Jennifer Laskey BWOSCC Medical Staff and Cancer Care Pharmacists WoS Pharmacy Cancer Network RCAG Prescribing Advisory Subgroup WOSCAN CINV V 1.0 Issue Date: September 2010 Review Date: September 2012 Page 5 of 5