Udated ASCO antiemetic guidelines for patients on chemotherapy and radiation therapy

The American Society of Clinical Oncology (ASCO) has updated the previously published guidelines from 2015 for antiemetic use. The guidelines specifically address prevention as well as treatment of nausea and vomiting due to antineoplastic therapy and radiation therapy in patients with cancer.ASCO has fully updated its antiemetic guideline for patients with cancer receiving chemotherapy and radiation therapy for the first time since 2015. The update is published online in the Journal of Clinical Oncology.

Most notably, the guideline provides new evidence-based information on the use of olanzapine as well as NK₁ receptor antagonists and dexamethasone.

1. Olanzapine, which is an antipsychotic medication, should be added to standard antiemetic regimens for adults who receive chemotherapy with a high risk for emesis or who experience breakthrough nausea and vomiting. High-risk regimens include use of cisplatin or the combination of cyclophosphamide and an anthracycline.The evidence for olanzapine comes from a large, double-blind, randomized, phase 3 study that compared the drug with placebo in patients who received the standard triple-drug antiemetic regimen of an NK1-receptor antagonist, a 5-HT₃-receptor antagonist, and dexamethasone.


2. In another key update, the ASCO guideline authors recommend adding an NK₁ receptor antagonist to the standard antiemetic regimen (the combination of 5-HT₃ receptor antagonist and dexamethasone) for adults receiving carboplatin-based chemotherapy or high-dose chemotherapy, and children receiving chemotherapy with a high risk for nausea and vomiting. NK₁ receptor antagonists include aprepitant, casopitant, and rolapitant.The quality of evidence for the addition of an NK₁ receptor antagonist is high and the strength of recommendation is strong, according to the guideline authors.


3. In another recommendation, the authors say that clinicians should administer dexamethasone only on day 1 for adults who receive anthracycline and cyclophosphamide chemotherapy.

Medical marijuana is not recommended in the new guidance, for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy. The evidence "remains insufficient," say the authors.However, the authors point out that ASCO guidance continues to recommend the US Food and Drug Administration-approved cannabinoids dronabinol or nabilone to treat nausea and vomiting that are resistant to standard antiemetic therapies.

Guideline Highlights

• ASCO organized an expert panel to develop updated recommendations to the guidelines published in 2015 based on both a systematic review of the literature as well as clinical experience.


• The panel searched PubMed and the Cochrane Library for literature published between November 1, 1999, and June 1, 2016, on antiemetics in oncology. They selected randomized controlled trials and meta-analyses of these trials.


• The authors updated the emetic risk potential associated with intravenous and oral antineoplastic agents from information from a 2016 publication by the Multinational Association of Supportive Care in Cancer and the European Society of Medical Oncology.


• The emetic potential associated with radiation therapy was classified into 4 risk categories depending on the anatomic region being irradiated.


• 41 publications including 35 randomized controlled trials and 6 meta-analyses were included. Although most of these studies evaluated chemotherapy-induced nausea and vomiting, 4 of the trials evaluated nausea and vomiting secondary to radiation therapy.


• Emetic risk associated with 19 new antineoplastic agents was included on information from 36 clinical trials.


• A 4-drug regimen is now recommended for adults receiving a high-emetic-risk regimen such as cisplatin. The 4-drug combination includes a NK₁ receptor antagonist, a 5-HT₃receptor antagonist, dexamethasone, and olanzapine all given on the first day of chemotherapy. Dexamethasone and olanzapine are continued on days 2 to 4 after chemotherapy administration.


• The 4-drug antiemetic regimen is based on data from a phase 3 trial in 380 patients completed in a trial by Navari and colleagues:
  
  
  
  • This trial evaluated the addition of olanzapine 10 mg or placebo on days 1 to 4 to a cisplatin-containing regimen.
  
  
  • All patients received an NK₁ receptor antagonist (either aprepitant or fosaprepitant), a 5-HT₃ receptor antagonist, and dexamethasone.
  
  
  • The number of patients with no nausea reported was significantly higher in the olanzapine vs the placebo group, from 0 to 24 hours (74% vs 45%), 24 to 120 hours, (42% vs 25%), and 0 to 120 hours (37% vs 22%) after cisplatin administration.
  
  
  • The complete response rate (no emetic episodes and no use of rescue medication) was also significantly higher in the olanzapine group at 0 to 24 hours, 24 to 120 hours, and 0 to 120 hours. The incidence of sedation was higher in the olanzapine group.
  
  
  
  


• Adult patients receiving an anthracycline such as a doxorubicin concurrently with cyclophosphamide should also receive the same 4-drug combination regimen.


• Adult patients receiving moderate-emetic-risk chemotherapy regimens that include carboplatin with an area under the curve (AUC) of 4 mg/mL per minute or more should receive a 3-drug regimen of a NK₁receptor antagonist, a 5-HT₃ receptor antagonist, and dexamethasone.


• For moderately emetic regimens that exclude carboplatin with an AUC of at least 4 mg/mL per minute, a 2-drug combination of a 5-HT₃ receptor antagonist (day 1) and dexamethasone (day 1) on day 1 are sufficient.


• For moderate-emetic-risk regimens that contain agents known to cause delayed nausea and vomiting (eg, cyclophosphamide, doxorubicin, and oxaliplatin), dexamethasone as a single agent is recommended on days 2 and 3.


• Low-emetic-risk regimens should be given in conjunction with single-agent dexamethasone or a 5-HT₃ receptor antagonist, whereas minimal-emetic-risk regimens should not include a scheduled antiemetic given prophylactically.


• Rolapitant, a NK₁ receptor antagonist approved since the last guidelines were published, has been evaluated in 4 randomized controlled clinical trials, and the guidelines recommend it as one of the NK₁receptor antagonist options.


• Subcutaneous extended-release granisetron, a 5-HT₃ receptor antagonist, has also been approved since the last guideline publication. It is a viable option for administration of a 5HT₃ antagonist.


• The guidelines include a statement that insufficient evidence is currently available to recommend use of medical marijuana for the prevention of chemotherapy or radiation-induced nausea and vomiting.


• For breakthrough nausea and vomiting in patients who have received the optimal prophylaxis based on the guidelines, subsequent scheduled prophylaxis should include olanzapine.


• For high-emetic-risk radiation therapy, a combination of a 5-HT₃ receptor antagonist and dexamethasone should be given before each fraction as well as on the day after each fraction.


• For patients receiving concurrent antineoplastic therapy with radiation, the antiemetic regimen should be selected based on the emetic risk of the antineoplastic agents unless the level of radiation emetic risk is higher.


• For a high-emetic-risk regimen in pediatric patients, olanzapine is not recommended. Rather, a 3-drug regimen consisting of a 5-HT₃ receptor antagonist, dexamethasone, and aprepitant should be given.


• For pediatric patients receiving high-emetic-risk regimens, the guidelines recommend a 2-drug regimen when there are reasons for the patient not to have the third agent.


• For pediatric patients receiving a moderate-emetic-risk regimen, a 2-drug combination of a 5-HT₃ receptor antagonist and dexamethasone should be offered. In patients unable to receive dexamethasone, the guidelines recommend a 5-HT₃receptor antagonist with aprepitant.


• A 5-HT₃ receptor antagonist (ondansetron or granisetron) should be given to pediatric patients receiving a low-emetic-risk regimen.

Clinical Implications

• Olanzapine, classified as an atypical antipsychotic, should be included as part of a 4-drug regimen in adult patients receiving a high-emetic-risk regimen such as cisplatin and for patients receiving an anthracycline concurrently with cyclophosphamide. The 4-drug combination includes the combination of a NK₁ receptor antagonist, a 5-HT₃ receptor antagonist, dexamethasone, and olanzapine all given on the first day of chemotherapy. Dexamethasone and olanzapine are continued on days 2 to 4 after chemotherapy administration.


• Patients receiving moderate-emetic-risk chemotherapy regimens that include carboplatin with an AUC of 4 mg/mL per minute or higher should also receive a 3-drug regimen of a NK₁ receptor antagonist, a 5-HT₃ receptor antagonist, and dexamethasone.


• A 2-drug regimen containing a 5-HT₃receptor antagonist and dexamethasone should be given before initiation of high-emetic-risk radiation therapy.

The guidelines from ASCO focus on first cycles of chemotherapy for patients in which the guidelines are most applicable. After initial cycles of chemotherapy, antiemetics may be tailored based on patient response regarding efficacy and toxicity of the initial antiemetic regimen.