Excerpt

Nausea and vomiting are common symptoms in cancer patients undergoing chemotherapy and radiation therapy. In some cases, failure to control nausea and vomiting in cancer patients may result in reduced nutritional status and quality of life, and may prompt the refusal of continuing chemotherapeutic and radiation therapy cycles. The benefits and harms of antiemetic regimens including a 5-hydroxytryptamine-3 (5-HT3) antagonist and a corticosteroid, with and without aprepitant, have been researched in many clinical studies. However, these antiemetic regimens need to be evaluated in the context of the specific programmatic interests of Centers for Medicare & Medicaid Services in terms of all-oral regimens compared with one another, all-oral regimens compared to all-injectable regimens, and mixed oral compared with injectable regimens. Additionally, the applicability of the evidence to patients age 65 and older needs to be determined.

This report compares the benefits and harms of antiemetic regimens that consist of a 5-HT3 antagonist plus a corticosteroid, with or without aprepitant, given to prevent and/or treat nausea and/or vomiting caused by emetogenic anticancer chemotherapy and/or radiation, and is based on a systematic review of the literature. The approach, methodology, and criteria used were agreed upon by consensus of staff at the Oregon Evidence-based Practice Center (EPC), Centers for Medicare & Medicaid Services (CMS), and the Agency for Healthcare Research and Quality (AHRQ). We assessed the internal validity (quality) of all studies based on predefined criteria. We graded the overall strength of evidence based on the guidance established for the Evidence-based Practice Center Program of AHRQ. The composite outcomes of total control (no emetic events, no rescue medication, none to mild nausea) and complete response (no emetic events, no rescue medication) were preferred to the individual outcomes of no emesis and no nausea. Applicability of the evidence was considered, with particular attention paid to whether the evidence was applicable to patients 65 years of age and older. Quantitative analyses were conducted where possible using Stats Direct (version 2.7.7, 9/13/2009). Random-effects models were used to estimate pooled relative risks and their 95% confidence intervals.

Contents

• Peer Reviewers
• EXECUTIVE SUMMARY
• INTRODUCTION
  • Purpose of the Report
  • Key Questions
  • Purpose and Limitations of Systematic Reviews
• METHODS
  • Search Strategy
  • Study Selection
  • Data Abstraction
  • Validity Assessment
  • Grading Strength of Evidence
  • Applicability
  • Data Synthesis
  • Peer Review and Public Comment
• RESULTS
  • Overview
  • Key Question 1 What are the comparative overall benefits of antiemetic regimens that consist of a 5-HT3 antagonist plus a corticosteroid, with or without aprepitant given to prevent and/or treat nausea and/or vomiting caused by emetogenic anticancer chemotherapy and/or radiation? Outcomes of interest include (at least): ability to control nausea and vomiting; ability to tolerate sequential chemotherapy sessions; quality of life measures
  • Key Question 2 What are the harms of antiemetic regimens that consist of a 5-HT3 antagonist plus a corticosteroid, with or without aprepitant, given to prevent and/or treat nausea and/or vomiting caused by emetogenic anticancer chemotherapy and/or radiation?
  • Key Question 3 Are there subgroups of patients based on demographics (age, race, gender), socioeconomic status, other medications, or comorbidities for which one of these antiemetic regimens is more effective or associated with fewer adverse events in the context of emetogenic anticancer chemotherapy and/or radiation?
• SUMMARY AND CONCLUSIONS
• REFERENCES
• ABBREVIATIONS USED IN THE REPORT
• APPENDICES
  • Appendix A US Food and Drug Administration recommendations for adult dosages
  • Appendix B Glossary
  • Appendix C Search strategies
  • Appendix D Methods to assess quality of studies
  • Appendix E Excluded studies
  • Appendix F Strength of evidence
  • Appendix G Data submitted by Merck Inc. through public comment process
• EVIDENCE TABLES

This report is based on research conducted by the OR EPC under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (I HHSA 290-2007-10057-I). The findings and conclusions in this document are those of the authors who are responsible for its contents. The findings and conclusions do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of the Agency for Healthcare Research and Quality or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decision-makers; patients and clinicians, health system leaders, and policymakers, make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

None of the investigators has any affiliations or financial involvement related to the material presented in this report.