Drug Class Review on Newer Antiemetics Final Report Evidence Tables 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 safety profiles of different drugs within pharmaceutical classes. 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 Sarah Lopez, BA Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2006 by Oregon Health & Science University Portland, Oregon 97201. 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 for scanning process description). The Drug Effectiveness Review Project governance group elected to proceed with another update of this report. Please see timeline on the DERP website for details on the date of its release. Final Evidence Tables Drug Effectiveness Review Project TABLE OF CONTENTS Evidence Table 1. Chemotherapy: head-to-head trials..............................................................3 Evidence Table 2. Quality assessments of the chemotherapy head-to-head trials ....................111 Evidence Table 3. Chemotherapy: placebo-controlled trials.....................................................144 Evidence Table 4. Quality assessments of the chemotherapy placebo-controlled trials ...........179 Evidence Table 5. Chemotherapy: active-controlled trials........................................................191 Evidence Table 6. Quality assessments of the chemotherapy active-controlled trials ..............205 Evidence Table 7. Radiation: controlled clinical trials..............................................................208 Evidence Table 8. Quality assessments for the radiation controlled clinical trials ...................228 Evidence Table 9. Prevention of PONV: head-to-head trials....................................................240 Evidence Table 10. Quality assessments of the head-to-head trials for the prevention of PONV........................................................................268 Evidence Table 11. Prevention of PONV: Active-controlled and placebo-controlled trials......274 Evidence Table 12. Quality assessment of active-controlled and placebo-controlled trials for prevention of PONV ...................................................................................298 Evidence Table 13. Treatment of established PONV: systematic reviews.................................310 Evidence Table 14. Treatment of established PONV: comparative clinical trials .....................316 Evidence Table 15. Quality assessments of the comparative clinical trials for treatment of established PONV.......................................................................................336 Evidence Table 16. Long-term uncontrolled intervention studies of safety and adverse events............................................................................339 Evidence Table 17. Quality assessment of long-term uncontrolled intervention studies of safety and adverse events ......................................................................................343 Newer Antiemetics Page 2 of 343 Final Evidence Tables 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 Open RCT children, females granisetron po 0.5 or 1.0mg no other antiemetics 4 wk run-in with 7.8 2004 Crossover ondansetron iv 0.45mg/kg allowed. antiemetics acc. to 64%male Multicenter rand. scheme/NR NR 3 once Forni DB RCT children Ondansetron iv 5.3mg/m2 Antiemetics were given NR/NR 16.9 2000 Parallel Granisetron iv 2mg/m2 with dexamethasone 8 69%male Not specified Tropisetron iv 3.3mg/m2 mg/m2 iv. NR 5 Newer Antiemetics Page 3 of 343 Final Evidence Tables 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 35/33/33 0/0/33 Acute lymphoblastic leukemia: 100% 2004 Multicenter 3 Forni NR/NR/90 NR/0/90 NR 2000 Not specified 5 Newer Antiemetics Page 4 of 343 Final Evidence Tables Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: head-to-head trials Author Year Setting Hesketh rating Results Children Jaing Granisetron vs Ondansetron 2004 Complete response: no emetic episodes and no need for rescue medication: Multicenter Within 24h: 60.6% vs 45.5%, NS 3 Incomplete response: 39.4% vs 54.5%, NS Therapeutic success: 84.8% vs 87.9%, NS Failure: ≥ 3 vomiting episodes in 24h study period: 15% vs 12%, NS Forni Results given as Ondansetron vs Granisetron vs Tropisetron 2000 Complete response (no vomiting or retching) Not specified Complete response : 58.3% vs 62.9% vs 57.1%, NS 5 Complete response: broken down by chemo regimen, not by study drug: 69% vs 44%, 0.0001 for ifos pts vs. cisplatin pts 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 Newer Antiemetics Page 5 of 343 Final Evidence Tables Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: head-to-head trials Author Year Setting Hesketh rating Adverse events Comments Children Jaing "The most frequently reported AEs were mild headache and constipation. No concomitant antiemetic therapy apart from the study drugs was given to 2004 The AEs were the same in both groups." the patients. Multicenter 3 Forni All patient days Population stratified by age owing to rarity of osteosarcoma; both pediatric 2000 Headache: 3.9% of 717 pt days, NR and adult pts entered study. Nausea data not collected because pediatric Not specified pts deemed not able to give reliable nausea data. Withdrawal data: No 5 Headache was the only AE the authors reported; they stated that it was of cases of dose reduction of antiblastics; in 2 pts the ifosfamide (ifo) cycle mild intensity and its frequency was the same in all 3 treatment groups. was stopped (on days 4 & 5 of infusion) because of neurotoxicity. 717 pt- days of treatment evaluated for 90 pts; results were given in terms of pt days. 3 pt days not evaluable: 2 Gran pts were not given ifo for 3 days total due to neurological problems. Children not analyzed as a subpopulation. In cisplatin-Adriamycin cycles the complete protection (CP) rate decreased 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. Newer Antiemetics Page 6 of 343 Final Evidence Tables 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 White DB RCT children, kinetosis Ondansetron iv 5mg/m2 Dexamethasone 2-4 mg No/NR 8 2000 Parallel Ondansetron po 8mg po was given along with 58%male Multicenter study antiemetics NR 4, 5 Newer Antiemetics Page 7 of 343 Final Evidence Tables 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 White NR/438/428 0/0/428 Mean weight (+/- SD) = 28.6 (+/- 12.2) kg 2000 Mean body surface area: (+/- SD) = 1.01 (+/- 0.30)m2 Multicenter Previous motion sickness: yes: 3% 4, 5 Newer Antiemetics Page 8 of 343 Final Evidence Tables Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: head-to-head trials Author Year Setting Hesketh rating Results White Ond iv vs Ond po 2000 Complete control of emesis (0 episodes) Multicenter Treatment phase A: 73% vs 71%, NS 4, 5 Overall (A+B): 62% vs 62%, NS Treatment Day 1: 81% vs 78%, NS Major control of emesis (1-2 episodes): Treatment A: 16% vs 17%, NS Overall (A+B): 23% vs 20%, NS Treatment Day 1: 10% vs 13%, NS Mild Nausea Treatment Day 1: 21% vs 21%, NS Phase A (a little bit nauseous): 26% vs 26%, NS Overall (A+B): 36% vs 33%, NS No nausea experienced: Treatment Day 1: 73% vs 70%, NS Overall (Phases A + B): 52% vs 56%, NS Phase A: 64% vs 64%, NS % with reduced appetite during treatment: increased by 7% from baseline vs increased by 12% from baseline, NS Newer Antiemetics Page 9 of 343 Final Evidence Tables Drug Effectiveness Review Project Evidence Table 1. Chemotherapy: head-to-head trials Author Year Setting Hesketh rating Adverse events Comments White Ond iv vs Ond po Ond po administered as an oral syrup, not a tablet. Study medication 2000 All Adverse Events: 20% vs 19%, NS administered during 2 phases: phases A and B. Treatment phase A Multicenter Abdominal/ gastronintestinal discomfort and pain: 4% vs 3%, NS involved each of the days (max. 8 days)