Modern Antiemetogenic Therapy

Educational Objectives

The goal of this program is to reduce chemotherapy-induced nausea and vomiting. After hearing and assimilating this program, the clinician will be better able to:

1. Choose appropriate drugs to prevent chemotherapy-induced nausea and vomiting (CINV).

2. Describe the pathways responsible for emesis in CINV.

Summary

Chemotherapy-induced nausea and vomiting (CINV)

Risk factors related to chemotherapy (CTX): include multiday dosing, high number of cycles, dose-dense regimen, high doses, short time of delivery, and emetogenicity of regimen (most important factor); cisplatin has high risk for emesis; drugs with moderate risk for emesis include doxorubicin and cyclophosphamide; high emetogenicity results from combining 2 drugs with moderate emetogenicity; paclitaxel is commonly used drug with minimal risk for emesis

Primary risk factors: risk for CINV increased in patients who undergo medical procedures (eg, surgery, radiation therapy) or receive certain medications (eg, nonsteroidal anti-inflammatory drugs, opioids, antibiotics); hypercalcemia, hepatic dysfunction, metastases to brain, and gastrointestinal (GI) abnormalities (eg, obstruction, ascites, hepatomegaly, gastroparesis) also increase risk

Secondary risk factors: CINV occurs more commonly in patients age <50 yr and in women; history of nausea and vomiting during pregnancy, chronic alcohol intake, and motion sickness increase likelihood of CINV; patients with high sensitivity to tastes and odors, anxiety or depression, or expectation of CINV also have higher risk

Timing of control: patients should take antiemetic medications in first 24 hr after CTX for best control

Grading criteria: grade 4 vomiting — patient vomits all fluids and foods and requires intravenous fluids; grade 3 vomiting — patient has >6 episodes of vomiting in 24 hr; grade 2 vomiting — patient has 2 to 5 episodes of vomiting in 24 hr; grade 3 nausea — patient unable eat

Treatments to control NV: include neurokinin-1 (NK1) inhibitors, serotonin antagonists (eg, ondansetron, granisetron [transdermal administration available]), steroids (eg, dexamethasone), phenothiazines, and metoclopramide (used when not controlled with conventional agents); side effects — 5-hydroxytryptamine3 (5-HT3) inhibitors (ondansetron) and butyrophenones increase risk for prolongation of QT interval; headache and constipation caused by 5-HT3 inhibitors; anticipatory NV — behavioral treatment best approach; timing — CINV may be acute or delayed; both require pharmacologic treatment

Effect of CTX on pathways: central pathway — activation causes release of substance P, which may stimulate NK1 receptors; significant in delayed phase of emesis; peripheral pathway — activation causes release of serotonin in GI tract which may activate 5-HT3 receptors; important in acute phase

Rolapitant: background — inhibits NK1 receptor; shown in 3 randomized trials to be effective against delayed vomiting; given as single dose of 180 mg; has long half-life (7 days) and does not induce or inhibit cytochrome P450; post hoc analysis of phase III trial — patients with breast cancer received 3 doses of granisetron and dexamethasone (DEX; ie, before CTX, day 2, day 3) with or without rolapitant; rolapitant group had more complete responses for prevention of delayed CINV; minimal side effects included constipation, headache, and fatigue in both treatment arms; authors concluded that patients receiving doxorubicin and cyclophosphamide can benefit from rolapitant

Phase III study of palonosetron: all 400 patients received palonestron plus aprepitant or fosaprepitant; patients were randomized to receive 3 days of DEX (days 1 to 3) vs 1 day of DEX (day 1); 76% of patients received doxorubicin and cyclophosphamide; no statistically significant difference in complete response rate seen between treatment arms; patients who received 3 days of DEX had more hot flashes and tremor; patients who received only 1 day of DEX had more anorexia, depression, and fatigue; authors concluded that treatment with DEX for 1 day not inferior to treatment with DEX for 3 days for prevention of CINV

Guidelines from National Comprehensive Cancer Network

Drugs with high risk for emesis: day 1 — recommend NK1 antagonist plus 5-HT3 antagonist plus steroid; may use DEX plus drug that combines netupitant (NK1 antagonist) and palonestron; may use olanzapine as adjunctive agent; days 2-4 — aprepitant requires additional doses on days 2-3; fosaprepitant and rolapitant require no additional doses, but do require additional doses of DEX

Drugs with moderate risk for emesis: allow for optional use of NK1 antagonist with recommended dose of 5-HT3 antagonist and steroid on days 1-3

Drugs with low risk for emesis: recommend DEX, metoclopramide, prochlorperazine, or 5-HT3 antagonist

Drugs with minimal risk for emesis: recommend no prophylaxis

Anticipatory nausea and vomiting: recommend behavioral therapy (eg, relaxation, systematic desensitization, music therapy), acupuncture, or low dose of antianxiety medication (eg, lorazepam)

Guidelines from American Society for Clinical Oncology: updated in 2015; drugs with high risk for emesis — recommend NK1 antagonist, 5-HT3 antagonist, and steroid; may use drug that combines netupitant and palonosetron; drugs with moderate risk for emesis — recommend 5-HT3 antagonist and steroid; NK1 antagonist not required if patient receiving, eg, carboplatin alone; drugs with low risk for emesis — recommend only corticosteroids for patients receiving etoposide; drugs with minimal risk or emesis — no prophylaxis recommended for patients receiving vinorelbine

Readings

Aapro M et al: Double-blind, randomized, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol 2010 May;21(5):1083-8; Celio et al: Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: A randomized, multicenter, phase III trial. Support Care Cancer 2011 Aug;19(8):1217-25; Gilmore JW et al: Antiemetic guideline consistency and incidence of chemotherapy-induced nausea and vomiting in US community oncology practice: INSPIRE study. J Oncol Pract 2014 Jan;10(1):68-74; Janicki PK: Management of acute and delayed chemotherapy-induced nausea and vomiting: Role of netupitant-palonosetron combination. Ther Clin Risk Manag 2016 May 2;12:693-9; Jordan K et al: Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings — a meta-analysis. Support Care Cancer 2016 May;24(5):1941-54; Navari RM et al: Antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. N Engl J Med 2016 Apr 7;374(14):1356-67.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Lavasani was recorded at the Best of ASCO: 2016 Annual Meeting, sponsored by Memorial Healthcare System and held July 8-10, 2016, in Miami, FL. For information about upcoming CME conferences from Memorial Healthcare System, please visit cme.mhs.net. The Audio Digest Foundation thanks the speakers and Memorial Healthcare System for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

ON072102

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.