呕吐MASCC

© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. MASCC/ESMO Antiemetic Guideline 2011 Multinational Association of Supportive Care in Cancer Organizing and Overall Meeting Chairs: Richard J. Gralla, MD Fausto Roila, MD Maurizio Tonato, MD Jørn Herrstedt, MD © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. These slides are provided to all by the Multinational Association of Supportive Care in Cancer and can be used freely provided no changes are made and the MASCC logo and date of the information are retained. For questions please contact: Rebecca Clark-Snow - rclark_snow@yahoo.com Chair, MASCC Antiemetic Study Group © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. •  This set of guideline slides represents the latest edition of the guideline process. •  This set of panels has been endorsed by the MASCC antiemetic guideline committee. •  The guidelines are based on the Perugia Consensus Conference on Antiemetic Therapy June 2009. •  Latest update April 2011. - A few comments on this guideline set - ANTIEMETIC GUIDELINE CONSENSUS: MASCC/ESMO © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. PARTICIPANTS IN THE PERUGIA ANTIEMETIC GUIDELINE PROCESS: MASCC/ESMO Matti Aapro, MD Enzo Ballatori, PhD Emilio Bria, MD Rebecca Clark-Snow, RN, BSN, OCN Lawrence Einhorn, MD Birgitte Espersen, RN Petra Feyer, MD Richard Gralla, MD Steven Grunberg, MD Jørn Herrstedt, MD Paul Hesketh, MD Karin Jordan, MD Mark Kris, MD Ernesto Maranzano, MD Alexander Molassiotis, RN, PhD Gary Morrow, PhD Ian Olver, MD, PhD Bernardo Rapoport, MD Cynthia Rittenberg, RN, MN, AOCN Fausto Roila, MD Mitsue Saito, MD Maurizio Tonato, MD David Warr, MD © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. CONTINENTS AND COUNTRIES OF PARTICIPANTS IN ANTIEMETIC GUIDELINE PROCESS: MASCC/ESMO Asia Africa Australia/Oceania Europe North America Japan South Africa Australia Denmark Germany France Italy Switzerland United Kingdom Canada United States of America © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. 5HT3 DEX APR 5HT3 DEX APR PALO DEX DEX + + + + + 5HT3 = serotonin receptor antagonist DEX = DEXAMETHASONE APR = APREPITANT PALO = PALONOSETRON SUMMARY ACUTE NAUSEA AND VOMITING EMETIC RISK GROUP ANTIEMETICS High + + Anthracycline + Cyclophosphamide (AC) + + Moderate (other than AC) + Low or or Minimal No routine prophylaxis 5HT3 DEX APR 5HT3 DEX APR PALO DEX DEX * NOTE: If the NK1 receptor antagonist is not available for AC chemotherapy, palonosetron is the preferred 5-HT3 receptor antagonist. The Antiemetic Subcommittee of The Multinational Association of Supportive Care in Cancer. - Ann Oncol 2010; www.mascc.org. 5HT3 DRA DRA = dopamine receptor antagonist © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. 5HT3 DEX APR 5HT3 DEX APR PALO DEX DEX + + + + + DEX = DEXAMETHASONE APR= APREPITANT SUMMARY DELAYED NAUSEA AND VOMITING EMETIC RISK GROUP ANTIEMETICS High + Anthracycline + Cyclophosphamide (AC) Moderate (other than AC) Low No routine prophylaxis Minimal No routine prophylaxis DEX APR APR DEX The Antiemetic Subcommittee of The Multinational Association of Supportive Care in Cancer. Ann Oncol 2010; www.mascc.org. © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. ANTIEMETIC GUIDELINES: MASCC/ESMO - The Process - 1)  Each committee worked on its area of concentration prior to the Perugia Meeting. At Perugia, each committee chair presented the findings of that committee to the entire group, and included the suggested rating of the level of evidence / confidence of the guideline. 2)  Group discussion and consensus voting then followed each presentation. What were the criteria for consensus? •  Degree of consensus required: 67% or greater agreement among the panelists was required to change a guideline. •  Basis of evidence to change an existing guideline: Compelling evidence was required based on well-conducted trials, generally with a comparator felt to be consistent with guidelines and representing best practice. Generally at least a 10% difference was considered to be the minimum degree of benefit sufficient for change. © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. ANTIEMETIC GUIDELINES: MASCC/ESMO - Committees and their Areas (1/2) - I.  Emetic classification of antineoplastic agents II.  Acute emesis: Highly emetic chemotherapy III.  Delayed emesis: Highly emetic chemotherapy IV.  Acute emesis: Moderately emetic chemotherapy V.  Delayed emesis: Moderately emetic chemotherapy © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. ANTIEMETIC GUIDELINES: MASCC/ESMO - Committees and their Areas (2/2) - VI. Emesis induced by minimal or low emetic risk chemotherapy VII. Additional Issues: Refractory emesis, rescue antiemetic therapy, multiple-day chemotherapy, high-dose chemotherapy VIII. Anticipatory emesis IXA. Radiotherapy-induced emesis IXB. Antiemetics in children receiving chemotherapy X. Future Considerations: Research Directions, Study Design, Economic Considerations © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. Ongoing process to address emerging evidence in the future: •  Committees are permanent •  Each chair queries the committee every 6 months regarding whether there is new information which may affect the guideline •  A steering committee queries the chairs for these suggestions •  If evidence appears compelling, all group members are notified for their opinions •  If consensus is achieved, the Web-Guideline document (MASCC) is updated. Keeping the Guidelines Accurate, Up-to-Date, and Valid ANTIEMETIC GUIDELINES: MASCC/ESMO Process for the future: © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. MASCC/ESMO Antiemetic Guidelines 2011 Committee I (1/5): The Four Emetic Risk Groups HIGH Risk in nearly all patients (> 90%) MODERATE Risk in 30% to 90% of patients LOW Risk in 10% to 30% of patients MINIMAL Fewer than 10% at risk © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. MASCC/ESMO Antiemetic Guidelines 2011 Committee I (2/5): Emetic Risk Groups – Single IV Agents HIGH Cisplatin Mechlorethamine Streptozocin Cyclophosphamide > 1500 mg/m2 Carmustine Dacarbazine MODERATE Oxaliplatin Cytarabine > 1000 mg/m2 Carboplatin Ifosfamide Cyclophosphamide < 1500 mg/m2 Azacitidine Alemtuzumab Doxorubicin Daunorubicin Epirubicin Idarubicin Irinotecan Bendamustine Clofarabine © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. MASCC/ESMO Antiemetic Guidelines 2011 Committee I (3/5): Emetic Risk Groups – Single IV Agents LOW Paclitaxel Docetaxel Mitoxantrone Topotecan Etoposide Pemetrexed Methotrexate Doxorubicin HCL liposome injection Temsirolimus Ixabepilone Mitomycin Gemcitabine Cytarabine < 1000 mg/m2 5-Fluorouracil Bortezomib Cetuximab Trastuzumab Catumaxomab Panitumumab © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. MASCC/ESMO Antiemetic Guidelines 2011 Committee I (4/5): Emetic Risk Groups – Single IV Agents MINIMAL Bleomycin Busulfan Cladribine Fludarabine Vinblastine Vincristine Vinorelbine Bevacizumab © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. MASCC/ESMO Antiemetic Guidelines 2011 Committee I (5/5): Emetic Risk Groups – Single Oral Agents HIGH Hexamethylmelamine Procarbazine MODERATE Cyclophosphamide Temozolomide Vinorelbine Imatinib LOW Capecitabine Tegafur Uracil Etoposide Sunitinib Fludarabine Everolimus Lapatinib Lenalidomide Thalidomide MINIMAL Chlorambucil Hydroxyurea Melphalan Methotrexate 6-Thioguanine Gefitinib Sorafenib Erlotinib © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE II: Guideline for the Prevention of Acute Nausea and Vomiting Following Chemotherapy of High Emetic Risk: To prevent acute nausea and vomiting following chemotherapy of high emetic risk, a three-drug regimen including single doses of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant (or fosaprepitant) given before chemotherapy is recommended. Level of confidence : High Level of consensus: High © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE III: Guideline for the Prevention of Delayed Nausea and Vomiting Following Chemotherapy of High Emetic Risk: In patients receiving cisplatin treated with a combination of aprepitant (or fosaprepitant), a 5-HT3 receptor antagonist and dexamethasone to prevent acute nausea and vomiting, the combination of dexamethasone and aprepitant is suggested to prevent delayed emesis, on the basis of its superiority to dexamethasone alone. Level of confidence: High Level of consensus: Moderate © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE IV (1/3): Guideline for the Prevention of Acute Nausea and Vomiting Following Chemotherapy of Moderate Emetic Risk: Women receiving a combination of anthracycline plus cyclophosphamide represent a situation with a particularly great risk of nausea and vomiting. To prevent acute nausea and vomiting, a three- drug regimen including single doses of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant (or fosaprepitant), given before chemotherapy is recommended. Level of confidence: High Level of consensus: High * NOTE: If the NK1 receptor antagonist is not available for AC chemotherapy, palonosetron is the preferred 5-HT3 receptor antagonist. © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE IV (2/3): Guideline for the Prevention of Acute Nausea and Vomiting Following Chemotherapy of Moderate Emetic Risk: In patients who receive chemotherapy of moderate emetic risk, not including a combination of anthracycline plus cyclophosphamide, palonosetron plus dexamethasone is recommended for prophylaxis of acute nausea and vomiting. Level of confidence: moderate Level of consensus: moderate © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE IV (3/3): Guideline for the Prevention of Acute Nausea and Vomiting Following Chemotherapy of Moderate Emetic Risk: The recommended dose of dexamethasone for prophylaxis of acute nausea and vomiting from chemotherapy of moderate emetic risk is 8 mg intravenously x 1. Level of confidence: Moderate Level of consensus: High © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. 5HT3 DEX APR 5HT3 DEX APR PALO DEX DEX + + + + + AGENT ROUTE ANTIEMETICS Ondansetron IV 8 mg or 0.15 mg/Kg Oral 16 mg* Granisetron IV 1 mg or 0.01 mg/Kg Oral 2 mg (or 1 mg**) Dolasetron Oral 100 mg*** Tropisetron IV 5 mg Oral 5 mg Palonosetron IV 0.25 mg Oral 0.5 mg Recommended Doses of Serotonin Receptor (5-HT3) Antagonists for Acute Emesis * Randomized studies have tested the 8 mg twice daily schedule ** The 1 mg dose preferred by some panelists *** Oral dosing recommended rather than IV due to potential QT interval prolongation © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. Recommended Corticosteroid* (dexamethasone) Dosing DEXAMETHASONE Dose and Schedule High Risk - Acute Emesis 20 mg once (12 mg when used with aprepitant or fosaprepitant)** - Delayed Emesis 8 mg bid for 3 - 4 days (8 mg once daily when used with aprepitant or fosaprepitant) Moderate Risk - Acute Emesis 8 mg once - Delayed Emesis 8 mg daily for 2 - 3 days (many panelists give the dose as 4 mg bid) Low Risk - Acute Emesis 4 - 8 mg once * While corticosteroids other than dexamethasone are effective antiemetics, the dose and schedule of dexamethasone coupled with its wide availability in various dose forms established it as the guideline agent of choice ** The 12 mg dose of dexamethasone is the only one tested with aprepitant in large randomized trials © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. Recommended NK1 Receptor Antagonist Dosing* APREPITANT and FOSAPREPITANT** Dose and Schedule - Acute Emesis Aprepitant: 125 mg orally, once on the day of chemotherapy - or - Fosaprepitant: 115 mg IV, once on the day of chemotherapy - Delayed Emesis Aprepitant 80 mg orally, once daily for the 2 days after chemotherapy * As of this update, Aprepitant and Fosaprepitant are the only approved antiemetic NK1 antagonists. ** Fosaprepitant is an intravenously administered pro-drug of aprepitant. In the countries in which fosaprepitant is available, it is indicated to replace the first day of oral aprepitant (125 mg) only. If either aprepitant or fosaprepitant is used on the day of chemotherapy, it should be followed on each of the next two days by oral aprepitant 80 mg daily. Fosaprepitant was approved on its similar pharmacokinetic profile (Lasseter et al. J Clin Pharm. 47, 834 - 840; 2007) when tested against aprepitant, not by comparative antiemetic clinical trials. © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE V (1/3): Guideline for the Prevention of Delayed Nausea and Vomiting Following Chemotherapy of Moderate Emetic Risk: Patients who receive moderately emetic chemotherapy known to be associated with a significant incidence of delayed nausea and vomiting should receive antiemetic prophylaxis for delayed emesis. Level of confidence: High Level of consensus: High © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE V (2/3): Guideline for the Prevention of Delayed Nausea and Vomiting Following Chemotherapy of Moderate Emetic Risk: In patients with breast cancer receiving a combination of anthracycline plus cyclophosphamide treated with a combination of aprepitant (or fosaprepitant), a 5-HT3 receptor antagonist and dexamethasone to prevent acute nausea and vomiting, aprepitant should be used to prevent delayed nausea and vomiting. MASCC Level of confidence: Moderate MASCC Level of consensus: Moderate © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. Guideline for the Prevention of Delayed Nausea and Vomiting Following Chemotherapy of Moderate Emetic Risk: In patients receiving chemotherapy of moderate emetic risk (which does not include a combination of anthracycline plus cyclophosphamide) in which palonosetron is recommended, multiday oral dexamethasone treatment is the preferred treatment for the prevention of delayed nausea and vomiting. Level of confidence: Moderate Level of consensus: Moderate COMMITTEE V (3/3): © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE VI (1/3): Guideline for prevention of acute nausea and vomiting in patients receiving low risk emetic agents: A single antiemetic agent such as dexamethasone, a 5-HT3 receptor antagonist or a dopamine receptor antagonist, such as metoclopramide, is suggested for prophylaxis in patients receiving agents of low emetic risk. Level of confidence: No confidence possible Level of consensus: Moderate © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. Guideline for prevention of acute nausea and vomiting in patients receiving minimal risk antineoplastic agents*: No antiemetic should be routinely administered before chemotherapy in patients without a history of nausea and vomiting. Level of confidence: No confidence possible Level of consensus: High *While unusual at this emetic level, if a patient experiences emesis it is advised that with subsequent chemotherapy treatments the regimen for the next higher emetic level should be given. COMMITTEE VI (2/3): © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE VI (3/3): Guideline for prevention of delayed nausea and vomiting in patients receiving low or minimal risk antineoplastic agents*: No antiemetic should be administered for the prevention of delayed emesis induced by low or minimally emetic chemotherapy. Level of confidence: No confidence possible Level of consensus: High *While unusual at this emetic level, if a patient experiences emesis it is advised that with subsequent chemotherapy treatments the regimen for the next higher emetic level should be given. © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE VII: Guideline for patients receiving multiple-day cisplatin: Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone for acute nausea and vomiting and dexamethasone for delayed nausea and vomiting. Level of confidence: High Level of consensus: High No guideline was felt to be appropriate for rescue antiemesis or high-dose (i.e. transplant) chemotherapy. 5-HT3 receptor antagonists should be dosed day 1-5, except for palonosetron that should be dosed on days 1, 3 and 5 only. Note: © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE VIII (1/2): Guidelines for prevention of anticipatory nausea and vomiting The best approach for anticipatory emesis is the best possible control of acute and delayed emesis. MASCC level of confidence: High MASCC level of consensus: High © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. Guideline for the prevention of anticipatory nausea and vomiting Behavioral therapies, in particular progressive muscle relaxation training, systematic desensitization and hypnosis, can be used to treat anticipatory nausea and vomiting. Level of confidence: High Level of consensus: High Benzodiazepines are the only drugs that reduced the occurrence of anticipatory nausea and vomiting but their efficacy tended to decrease as chemotherapy treatments continue. Level of confidence: Moderate Level of consensus: Moderate COMMITTEE VIII (2/2): © 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide. COMMITTEE IXA (1/5) - Levels of Emetic Risk with Radiation Therapy - RISK LEVEL