Roila, F., Herrstedt, J., Aapro, M., Gralla, R.J., Einhorn, L.H., Ballatori, E., … ESMO/MASCC Guidelines Working Group. (2010). Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: Results of the Perugia consensus conference. Annals of Oncology, 21(Suppl. 5), v232–v243.

This Perugia consensus panel was composed of 10 committees that reported findings to a 23-member expert panel from 10 different countries. The panel determined level of evidence and made changes in 2004 guidelines if evidence supported a greater than 10% increase in benefit. Updates were approved by the European Society of Medical Oncology (ESMO) Guidelines Working Group. All author relationships were reported. The panel used MEDLINE and other databases, which were not specified.

Emetogenicity of agents:

• As new agents are developed, often limited recording of common toxicities is provided in order to accurately reflect emetogenic potential.
• Increased use of oral agents and chronic oral administration creates issues regarding whether emetogenicity is defined by a single dose or a full course, and chronic use has blurred the lines between acute and delayed chemotherapy-induced nausea and vomiting (CINV).
• The authors provided an updated list of chemotherapy agents and levels of emetogenicity. Classification of oral agents was provided on the basis of a full course of treatment.

Prevention of acute CINV:

• Minimal risk: No routine prophylaxis
• Low risk: Day 1—dexamethasone or 5-HT₃ receptor antagonists or dopamine receptor antagonist
• Moderate emetogenic chemotherapy (MEC)
  • With anthracycline: Day 1—5-HT₃ receptor antagonist + dexamethasone + aprepitant or fosaprepitant; days 2 and 3—aprepitant
  • Without anthracycline: Day 1—palonosetron + dexamethasone; days 2 and 3—dexamethasone
• Highly emetogenic chemotherapy (HEC): Day 1—5-HT₃ receptor antagonist + dexamethasone + aprepitant or fosaprepitant; days 2 and 3—dexamethasone + aprepitant; day 4—dexamethasone
• Although studies have shown effectiveness of casopitant, the producer discontinued regulatory filings, so this was not recommended for use.
• All 5-HT₃ receptor antagonists were found to show the same efficacy. More studies are needed to determine if palonosetron is more effective with cisplatin-based therapies.

Prevention of delayed CINV:

• Aprepitant should be used to prevent delayed CINV.
• Whether dexamethasone is as effective or if the combination of dexamethasone and aprepitant would be more effective is not known. The optimal dose and duration of dexamethasone is not defined.
• Prevention with multiple-day cisplatin was not clear. Aprepitant + dexamethasone for acute and dexamethasone for delayed CINV was recommended. The possible role of ​neurokinin 1 (NK1) was not clear.

Refractory CINV and rescue:

• Maximally effective prophylaxis should be used.
• The addition of cannabinoids, olanzapine, and nonpharmacologic interventions could be considered.

Prevention of anticipatory CINV:

• The best way to prevent this learned response is maximum effective control of acute and delayed CINV.
• Anticipatory CINV is difficult to control with medication.
• Benzodiazepines are the only drugs identified as effective, but efficacy tends to decrease as chemotherapy continues.

Prevention of CINV with high-dose chemotherapy:

• Complete protection is currently only achieved in a minority of patients.
• Current standard is dexamethasone + 5-HT₃ receptor antagonists.
• Evaluation of the addition of aprepitant is needed.

Radiation-induced nausea and vomiting:

• Risk level and antiemetic guidelines are provided.
• Generally, prophylaxis with 5-HT₃ receptor antagonists + dexamethasone and rescue with 5-HT₃ receptor antagonists are recommended.

Antiemetics in children:

• All pediatric patients receiving MEC or HEC should receive prophylaxis with 5-HT₃ and dexamethasone. Optimal dosing requires further study.
• No studies have evaluated approaches for prevention of anticipatory CINV.
• Metoclopramide, phenothiazines, and cannabinoids have shown only moderate efficacy.

The guidelines provide a clear set of recommendations and review of the relevant evidence strength assessed for various cancer treatment scenarios.

A complete listing of databases used for evidence retrieval was not provided.

Control of emesis has markedly improved in recent years; however, nausea remains a challenge and future research should shift attention to this aspect. Current trials generally define complete response end points that exclude consideration of the experience of nausea rather than vomiting. Trials suggest that some agents are more effective for acute vomiting, others are more effective for delayed vomiting, and some may be more effective for nausea. Identification of these differences and incorporation into the rationale for treatment needs to continue.

Further research is needed in the areas of prevention with high-dose chemotherapy and stem cell support, combined chemotherapy and radiation therapy, and anticipatory nausea and antiemetic use in children. Practitioners need to be aware of the impact of oral therapy and chronic oral chemotherapy treatment on current approaches to antiemetic treatment, timing, and definitions of acute and delayed CINV. Practitioners also need to be aware that current chemotherapy risk determination does not apply to combined radiotherapy and chemotherapy.