Drug Class Review Newer Antiemetics Final Report Update 1 Evidence Tables January 2009 Original Report: January 2006 A literature scan of this topic is done periodically The purpose of this report is to make available information regarding the comparative effectiveness and harms of different drugs. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Kimberly Peterson, MS Marian McDonagh, PharmD Susan Carson, MPH Sujata Thakurta, MPA: HA Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2008 by Oregon Health & Science University Portland, Oregon 97239. All rights reserved. Note: A scan of the medical literature relating to the topic is done periodically (see http://www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/methods.cfm). Upon review of the last scan, the Drug Effectiveness Review Project governance group elected not to proceed with another full update of this report. Some portions of the report may not be up to date. Prior versions of this report can be accessed at the DERP website. Final Report Update 1 Drug Effectiveness Review Project TABLE OF CONTENTS Evidence Table 1. Chemotherapy: head-to-head trials ..............................................................4 Evidence Table 2. Quality assessments of the chemotherapy head-to-head trials ....................140 Evidence Table 3. Chemotherapy: placebo-controlled trials .....................................................182 Evidence Table 4. Quality assessments of the chemotherapy placebo-controlled trials ...........236 Evidence Table 5. Chemotherapy: active-controlled trials ........................................................256 Evidence Table 6. Quality assessments of the chemotherapy active-controlled trials ..............277 Evidence Table 7. Radiation: controlled clinical trials ..............................................................280 Evidence Table 8. Quality assessments for the radiation controlled clinical trials ...................300 Evidence Table 9. Prevention of PONV: head-to-head trials ....................................................309 Evidence Table 10. Quality assessments of the head-to-head trials for the prevention of PONV ........................................................................369 Evidence Table 11. Prevention of PONV: Active-controlled and placebo-controlled trials ......387 Evidence Table 12. Quality assessment of active-controlled and placebo-controlled trials for prevention of PONV ...................................................................................426 Evidence Table 13. Treatment of established PONV: systematic reviews .................................447 Evidence Table 14. Treatment of established PONV: comparative clinical trials .....................455 Evidence Table 15. Quality assessments of the comparative clinical trials for treatment of established PONV .......................................................................................483 Evidence Table 16. Long-term uncontrolled intervention studies of safety and adverse events ............................................................................489 Evidence Table 17. Quality assessment of long-term uncontrolled intervention studies of safety and adverse events ......................................................................................493 Antiemetics Page 3 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Age Setting Allow other Gender Hesketh rating Design Subpopulation Intervention medication Run-in/ Wash-out Ethnicity Children Jaing granisetron po 0.5 or 1.0mg 4 wk run-in with 7.8 2004 Open RCT ondansetron iv 0.45mg/kg no other antiemetics Children, females antiemetics acc. to 64%male Multicenter Crossover allowed. rand. scheme/NR NR 3 once Forni Ondansetron iv 5.3mg/m2 Antiemetics were given 16.9 2000 DB RCT Children Granisetron iv 2mg/m2 with dexamethasone 8 NR/NR 69%male Not specified Parallel Tropisetron iv 3.3mg/m2 mg/m2 iv. NR 5 Antiemetics Page 4 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Screened/ Withdrawn/ Setting Eligible/ Lost to fu/ Hesketh rating Enrolled Analyzed Other population characteristics Children Jaing 2004 35/33/33 0/0/33 Acute lymphoblastic leukemia: 100% Multicenter 3 Forni 2000 NR/NR/90 NR/0/90 NR Not specified 5 Antiemetics Page 5 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Setting Hesketh rating Results Children Granisetron vs Ondansetron Jaing Complete response: no emetic episodes and no need for rescue medication: 2004 Within 24h: 60.6% vs 45.5%, NS Multicenter Incomplete response: 39.4% vs 54.5%, NS 3 Therapeutic success: 84.8% vs 87.9%, NS Failure: ≥ 3 vomiting episodes in 24h study period: 15% vs 12%, NS Results given as Ondansetron vs Granisetron vs Tropisetron Forni Complete response (no vomiting or retching) 2000 Complete response : 58.3% vs 62.9% vs 57.1%, NS Not specified Complete response: broken down by chemo regimen, not by study drug: 69% vs 44%, 0.0001 for ifos pts vs. cisplatin pts 5 Partial response, % of patient days (1-4 episodes of vomiting/day): 34.2% vs 28.2% vs 38.3%, NS Failure (≥5 episodes of vomiting/day) % of patient days: 7.5% vs 8.9% vs 4.6%, NS Antiemetics Page 6 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Setting Hesketh rating Adverse events Comments Children Jaing 2004 "The most frequently reported AEs were mild headache and constipation. No concomitant antiemetic therapy apart from the study drugs was given to Multicenter The AEs were the same in both groups." the patients. 3 Population stratified by age owing to rarity of osteosarcoma; both pediatric and adult pts entered study. Nausea data not collected because pediatric pts deemed not able to give reliable nausea data. Withdrawal data: No cases of dose reduction of antiblastics; in 2 pts the ifosfamide (ifo) cycle was stopped (on days 4 & 5 of infusion) because of neurotoxicity. 717 pt- All patient days days of treatment evaluated for 90 pts; results were given in terms of pt Forni Headache: 3.9% of 717 pt days, NR days. 3 pt days not evaluable: 2 Gran pts were not given ifo for 3 days total 2000 due to neurological problems. Children not analyzed as a subpopulation. In Not specified Headache was the only AE the authors reported; they stated that it was of cisplatin-Adriamycin cycles the complete protection (CP) rate decreased 5 mild intensity and its frequency was the same in all 3 treatment groups. from 61% on day 1 to 27% on day 2. On the third day when Adriamycin was given, the total protection=44% (P<0.0001). During ifo cycles CP decreased from 95.5% on day1 to 43% on the last (P<0.0001). 10% of pts experienced CP on all treatment days during both chemo types. CP was achieved in 19% only for one type of chemo cycle; the remaining 71% experienced emesis in both cycles for at least 1 day. Antiemetics Page 7 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Age Setting Allow other Gender Hesketh rating Design Subpopulation Intervention medication Run-in/ Wash-out Ethnicity Sepulveda- Mean age: 11years Vildosola RCT, DB, Ondansetron IV 8mg/m2 Range: 2-15 2008 None NR NR/NR Parallel Palonosetron IV 0.25mg 69% males Single Center Ethnicity: NR 2-5 Antiemetics Page 8 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Screened/ Withdrawn/ Setting Eligible/ Lost to fu/ Hesketh rating Enrolled Analyzed Other population characteristics Sepulveda- Vildosola Previous treatment with chemotherapy: 86% 2008 NR/NR/100 NR/NR/100 Nausea or vomiting in previous chemotherapy: 76% Single Center 2-5 Antiemetics Page 9 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Setting Hesketh rating Results Palonosetron vs Ondansetron Complete control of emetic events at day 1: 92% vs 72% Complete control of emetic events at day 2: 72% vs 46% Complete control of emetic events at day 3: 78% vs 54% Complete control of emetic events at day 4: 88% vs 84% Sepulveda- Complete control of emetic events at day 5: 98% vs 90% Vildosola Complete control of emetic events at day 6: 100% vs 94% 2008 Complete control of emetic events at day 7: 100% vs 96% Single Center 2-5 Absence of nausea at day 1: 74% vs 38% Absence of nausea at day 2: 62% vs 18% Absence of nausea at day 3: 72% vs 30% Absence of nausea at day 4: 88% vs 58% Absence of nausea at day 5: 98% vs 88% Absence of nausea at day 6: 98% vs 92% Absence of nausea at day 7: 98% vs 94% Antiemetics Page 10 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Setting Hesketh rating Adverse events Comments Sepulveda- Vildosola 2008 NR Single Center 2-5 Antiemetics Page 11 of 493 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: Head-to-head trials Author Year Age Setting Allow other Gender Hesketh rating Design Subpopulation