High-emetogenic-risk drugs include combination anthracycline/cyclophosphamide, carmustine, cisplatin, cyclophosphamide (≥ 1,500 mg/m2), dacarbazine, mechlorethamine, and streptozocin.4

Moderately emetogenic drugs include:

• Alemtuzumab
• Azacitidine
• Bendamustine
• Carboplatin
• Clofarabine
• Cyclophosphamide (< 1,500 mg/m2)
• Cytarabine (> 1,000 mg/m2)
• Daunorubicin
• Doxorubicin
• Epirubicin
• Idarubicin
• Ifosfamide
• Irinotecan
• Irinotecan liposomal injection
• Oxaliplatin
• Romidepsin
• Temozolomide
• Thiotepa
• Trabectedin

Low-emetogenicity chemotherapy agents include:

• Aflibercept
• Atezolizumab
• Belinostat
• Blinatumomab
• Bortezomib
• Brentuximab
• Cabazitaxel
• Carfilzomib
• Catumaxomab
• Cetuximab
• Cytarabine (≤ 1,000 mg/m2)
• Docetaxel
• Elotuzumab
• Eribulin
• Etoposide
• Fluorouracil
• Gemcitabine
• Ipilimumab
• Ixabepilone
• Methotrexate
• Mitomycin
• Mitoxantrone
• Nab-paclitaxel
• Necitumumab
• Paclitaxel
• Panitumumab
• Pemetrexed
• Pegylated liposomal doxorubicin
• Pertuzumab
• Temsirolimus
• Topotecan
• Trastuzumab-emtansine
• Vinflunine

Minimally emetogenic chemotherapies include:

• Bevacizumab
• Bleomycin
• Busulfan
• 2-Chlorodeoxyadnosine
• Cladribine
• Daratumumab
• Fludarabine
• Nivolumab
• Obinutuzumab
• Ofatumumab
• Pembrolizumab
• Pixantrone
• Pralatrexate
• Ramucirumab
• Rituximab
• Trastuzumab
• Vinblastine
• Vincristine
• Vinorelbine

Acute, Delayed, and Anticipatory Nausea and Vomiting

Acute nausea and vomiting occur within 24 hours of administration or exposure and delayed cases occur more than 24 hours after administration or exposure.1 The severity of nausea and vomiting can range from diminished appetite without changed eating habits to life-threatening consequences (Table 1).

TABLE 1. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events: Nausea & Vomiting1,7

Adverse Event Grade  Description 
Nausea  Loss of appetite without alteration in eating habits
  2 Oral intake decreased without significant weight loss, dehydration, or malnutrition
  3 Inadequate oral caloric or fluid intake; tube feeding; total parenteral nutrition (TPN), or hospitalization indicated
Vomiting 1 1-2 episodes (separated by 5 min) in 24 h
  2 3-5 episodes (separated by 5 min) in 24 h
  3 ≥6 episodes (separated by 5 min) in 24 h; tube feeding, TPN, or hospitalization indicated
  4 Life-threatening consequences; urgent intervention indicated
  5 Death

For RINV, the patient anatomy that is to be irradiated is used to determine the emetogenic potential of treatment. For example, total body irradiation and total nodal irradiation carry a high (> 90%) risk of emesis in the absence of antiemetic prophylaxis, while breast and limb irradiation carries a minimal (< 30%) risk of emesis without prophylaxis.1 Upper-abdominal, upper-body, and hemibody irradiation carry a moderate (60% – 90%) risk of RINV and cranial, craniospinal, head and neck, pelvic, or lower thorax radiotherapy all carry a low (30% – 60%) risk of RINV.1

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Some chemotherapy agents are more strongly associated with delayed nausea and vomiting than others. These include cisplatin, cyclophosphamide, doxorubicin, and ifosfamide when administered for 2 or more days in a row, or at higher doses.1,4 Electrolyte imbalances; hypercalcemia; tumor growth in the liver, gastrointestinal tract,  or brain; opioids; infection; and constipation each also appear to contribute to treatment-related nausea and vomiting.1 Risk factors for delayed CINV include acute CINV, female sex, patient age younger than 50 years, previous chemotherapy or recent or concurrent radiotherapy history, malnutrition, dehydration, or a history of pregnancy- or motion-induced nausea and vomiting.1 For reasons that are not yet well understood, chronic alcohol use appears to be associated with a reduced risk of CINV.3

In addition to acute and delayed emesis, breakthrough or refractory nausea and vomiting occurs despite antiemetic pharmacotherapy, necessitating switching treatment and the use of rescue medication.3,4

Between 1.5% and 8% of patients experience pretreatment “anticipatory” nausea.5 Anticipatory nausea is believed to involve classical conditioning, in which memory of a previous emetogenic stimulus triggers a conditioned response — in this case, previous poorly managed CINV.1,3,5 Anticipatory nausea does not respond as well to antiemetic pharmacotherapies as acute or delayed cancer treatment-associated emesis.5 According to the NCI, a number of nonpharmacologic interventions have been proposed for anticipatory emesis, including hypnosis, guided imagery, biofeedback, and distraction with video games.1