Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of many cancer treatments. Nausea and vomiting are two of the most feared cancer treatment-related side effects for cancer patients and their families. In 1983, Coates et al. found that patients receiving chemotherapy ranked nausea and vomiting as the first and second most severe side effects, respectively. Up to 20% of patients receiving highly emetogenic agents in this era postponed, or even refused, potentially curative treatments. Since the 1990s, several novel classes of antiemetics have been developed and commercialized, becoming a nearly universal standard in chemotherapy regimens, and helping to better manage these symptoms in a large portion of patients. Efficient mediation of these unpleasant and sometimes debilitating symptoms results in increased quality of life for the patient, and better overall health of the patient, and, due to better patient tolerance, more effective treatment cycles.
Types
There are several subtypes of CINV. The classifications of nausea and vomiting are: Acute: occurring within 24 hours of chemotherapy Delayed: occurring between 24 hours and 5 days after treatment Breakthrough: occurring despite prophylactic treatment Anticipatory: triggered by taste, odor, memories, visions, or anxiety related to chemotherapy Refractory: occurring during subsequent cycles when antiemetics have failed in earlier cycles
Cause
Emesis is a defense mechanism controlled by the area postrema of the medulla oblongata. There are various sources of input to the vomiting center. Receptors on the floor of the fourth ventricle of the brain represent the chemoreceptor trigger zone. The chemoreceptor trigger zone contains dopamine D2 receptors, serotonin 5-HT3 receptors, opioid receptors, acetylcholine receptors, and receptors for substance P. Stimulation of different receptors are involved in different pathways leading to emesis. In the final common pathway, substance P, which activates the neurokinin-1 receptor, appears to be involved. Additionally, the vagal and enteric nervous system inputs transmit information regarding the state of the gastrointestinal system.
Chemotherapy interferes with cell division, which particularly affects rapidly dividing cells like those of the gastrointestinal mucosa and immune cells. Irritation of the GI mucosa by chemotherapy, radiation, distention, or acute infectious gastroenteritis activates the 5-HT3 receptors of these inputs. It is now widely known that cytotoxic chemotherapeutic agents cause enterochromaffin cells to produce more serotonin in response to free radical damage, leading to a detectable increase in blood levels of serotonin (5-HT) and its major metabolite, 5-Hydroxyindoleacetic acid (5-HIAA). The presence of these chemicals in the blood activate 5-HT3 receptors in the chemoreceptor trigger zone, in turn releasing substance P, which activates NK1 receptors to cause an emetic response (vomiting).
Risk factors
The risk of chemotherapy-induced nausea and vomiting varies based on the type of treatment received as well as several outside factors. Some types of chemotherapy are more prone to causing nausea and vomiting than others. Some chemotherapeutic agents may not cause nausea and vomiting on their own, but may when used in combination with other agents. Regimens that are linked to a high incidence (90% or higher) of nausea and vomiting are referred to as "highly emetogenic chemotherapy", and those causing a moderate incidence (30–90%) of nausea and vomiting are referred to as "moderately emetogenic chemotherapy".
Some highly emetogenic agents and chemotherapy regimens include: ABVD AC BEP Cisplatin Carmustine (>250 mg/m2) CBV Cyclophosphamide (>1500 mg/m2) Dacarbazine Mechlorethamine MOPP/COPP/BEACOPP Streptozocin VIP
Some moderately emetogenic agents and regimens include: Carboplatin CHOP/CHOP-R Cyclophosphamide (≤1500 mg/m2) Docetaxel Doxorubicin/Adriamycin Etoposide Ifosfamide Methotrexate Paclitaxel
Besides the type of treatment, personal factors may put a patient at greater risk for CINV. Other risk factors include: Anticipation of CINV Anxiety or depression Female sex History of light alcohol use History of motion sickness History of nausea and vomiting during pregnancy History of previous CINV Patient age (under 55 years old)
Treatments
Several treatment methods are available to help prevent CINV. Pharmaceutical treatment is generally separated into two types: prophylactic (preventative) treatment, given before the dose of chemotherapy agents, and rescue treatment, given to treat breakthrough nausea and vomiting.