Frame, D.G. (2010). Best practice management of CINV in oncology patients: I. Physiology and treatment of CINV. Multiple neurotransmitters and receptors and the need for combination therapeutic approaches. Journal of Supportive Oncology, 8(2, Suppl. 1), 5–9.

• This article reviewed the neurotransmitter and receptor systems involved with chemotherapy-induced nausea and vomiting (CINV) and a brief history of development of antiemetic therapies. CINV classifications was defined as follows.
  • Acute—occurring and resolving within 24 hours of chemotherapy
  • Delayed—occurring more than 24 hours after chemotherapy administration
  • Breakthrough—occurring despite antiemetic therapy
  • Refractory—unmanageable with current antiemetics
  • Anticipatory—conditioned response after prior inadequately controlled CINV.
• The article stated that anticipatory CINV is the most common kind.
• The article reviewed the mechanism of action and current knowledge regarding common antiemetic regimens and noted that given the physiology involved, optimal treatment requires a combination of therapies targeting multiple systems.

• Dexamethasone in combination with 5-HT₃ receptor antagonists is recommended (unless contraindicated or not tolerated). The author noted that this is too often not included.
• In delayed emesis, metoclopramide has been shown to be equivalent to ondansetron in controlling delayed CINV. Metoclopramide is also associated with extrapyramidal symptoms.
• Differences among 5-HT₃ receptor antagonists were noted.
  • Among first generation drugs, overall efficacy of the agents are similar.
  • Palonosetron is a second generation drug with a longer half-life, which appears to be associated with some preventive benefits.
  • Results of studies indicate that without some combination therapy, these drugs alone will fail in 40%–50% of patients.
  • The author noted that some individuals have a genetic tendency to metabolize these drugs differently and those with ultra-rapid metabolism have less therapeutic benefit. Palonosetron appears to have a smaller effect in this area.
• The effects of 2 mg per day of oral granisetron and 3.1 mg per day via epidermal patch appear to be similar.
• The addition of aprepitant (a neurokinin 1 [NK1] antagonist) to 5-HT₃ receptor antagonists and dexamethasone has demonstrated success. A larger benefit has been found for women than for men. The current approved regimen for aprepitant is a three-day regimen; however, ongoing studies are under way to determine if additional doses are helpful. When using aprepitant, the dexamethasone dosage should be reduced. A potential interaction between aprepitant and chemotherapeutic agents such as ifosfamide have been noted. In one study, the combination was associated with increased neurotoxicity.
• Olanzapine is an antipsychotic that blocks multiple neurotransmitters involved in CINV. Trials of olanzapine in combination with granisetron plus dexamethasone and palonosetron plus dexamethasone have demonstrated effectiveness in preventing CINV.

This article demonstrated the importance of combination therapy for prevention and management of CINV. The author provides a good overview of relevant physiology, mechanism of action of current agents, and current regimens used. The article points to the need for additional research with the use of olanzapine for CINV.