When patients are informed that they will need to undergo chemotherapy, the anticipation of nausea and vomiting often arises as one of the foremost concerns. In a study conducted in 2005, individuals battling ovarian cancer and undergoing chemotherapy were requested to assess the intensity of various symptoms. The results indicated that the experience of severe nausea and vomiting was likened to feeling like they were going to die. [Support Care Cancer. 2005;13:219-227]

In recent times, advancements in chemotherapy have led to the development of drugs with fewer side effects, including those targeting nausea and vomiting. Consequently, the occurrence of these side effects has notably diminished. However, this progress has been gradual, resulting in a persistent association between chemotherapy and the perception of nausea and vomiting for many individuals.

Why does chemotherapy cause nausea and vomiting? 

The cause of chemotherapy-induced nausea and vomiting is not fully clear, but it's believed to involve multiple factors. Chemotherapy drugs impact the brain, responsible for vomiting, and gut cells, which release nausea-related neurotransmitters like serotonin, Substance P, and dopamine. Current anti-nausea drugs work by blocking these neurotransmitters. [Engl J Med 2016;374:1356-67]

In 1978, the approval of the chemotherapy drug cisplatin marked an improvement in outcomes, although it was associated with significant vomiting for most patients. In 1990, a study demonstrated that serotonin blockers could effectively curb chemotherapy-induced vomiting, leading to a decline in its occurrence. 

Subsequently, in 2003, a study introducing the blocker Substance P was published and the agent was approved. This led to a substantial reduction of chemotherapy-induced vomiting to around 10 percent. 

Prevention is more important

In light of drug advancements and research, the employment of serotonin blockers, Substance P blockers, and steroids has become commonplace to preempt nausea and vomiting before chemotherapy, tailored to the likelihood of side effects. This preventive approach holds greater significance as mitigating these symptoms outweighs addressing them post-occurrence. These side effects can significantly impair the quality of life and compromise treatment adherence.

Furthermore, preempting nausea and vomiting side effects holds significance in averting a phenomenon known as anticipatory vomiting, wherein patients vomit prior to the commencement of the subsequent chemotherapy cycle. In cases where despite precautions, nausea and vomiting arise, active symptom management can be pursued using medications like dopamine blockers. In instances of severe symptoms, the preventive medication might be intensified or the chemotherapy dose adjusted in subsequent treatments.

Steroids as an anti-emetic?

Steroids are administered before chemotherapy to prevent hypersensitivity reactions and also to mitigate the occurrence of nausea and vomiting. They are employed across low- and moderate-risk patient groups with varying levels of vomiting risk. While they might be omitted in low-risk patients, they are generally used in moderate- and high-risk patients unless contraindicated. The precise mechanisms through which steroids curtail nausea and vomiting are not fully elucidated. Still, they seem to diminish the inflammatory response triggered by chemotherapy, directly influence the vomiting center, and impact other neurotransmitters. Additionally, in situations of stress, steroids can help sustain normal physiological function, thereby reducing symptoms. [Eur J Pharmacol. 2014 Jan 5;722:48-54]

Dexamethasone is the steroid commonly employed for this purpose. Variations in its dosage across different studies initially prompted questions about the appropriate amount to use. However, a meta-analysis conducted in 2000 resolved this uncertainty, establishing the current dosage standards. [J Clin Oncol. 2000;18(19):3409]

The doses of dexamethasone analyzed in the referenced paper ranged from 8 mg to 100 mg. When arranged by dose, no consistent dose-response relationship was evident, with a slight potential association observed at doses below 20 mg. Consequently, current guidelines advocate using 20 mg of dexamethasone for high-risk chemotherapy-induced vomiting. In the U.S., the NCCN guidelines propose a 12 mg dose. Notably, the meta-analysis study did not demonstrate a significant difference in odds ratios between 12 mg and 20 mg. This suggests that the 12 mg dose is acceptable and reasonable.

Psychiatric medications

The drug olanzapine has emerged as a viable option in guidelines for preventing chemotherapy-induced vomiting. As an atypical antipsychotic, olanzapine functions by blocking serotonin and dopamine receptors—neurotransmitters linked to nausea and vomiting, as discussed earlier. By simultaneously targeting both receptors, olanzapine has proven effective in thwarting chemotherapy-induced nausea and vomiting. Research indicates its compatibility with existing medications, enhancing symptom control. Notably, olanzapine has the potential to supplant the use of steroids, which carry side effects like unstable blood sugar levels and hiccups. Moreover, steroids can compromise the efficacy of immuno-oncology drugs when combined with conventional antitumor agents. Given these factors, the increasing adoption of olanzapine appears likely in the future.

Nausea and vomiting consistently rank as the primary concerns among the challenges encountered by patients undergoing chemotherapy, as evidenced by research. Historically, patients were encouraged to endure these symptoms, but the landscape of supportive care has advanced to alleviate this discomfort. It is essential to redouble efforts in facilitating access to appropriate treatments, aiming to alleviate the burden for patients undergoing chemotherapy.

Professor Kim Dal-yong graduated from Kyung Hee University School of Medicine and completed his internship and residency at Asan Medical Center. He served as a clinical instructor in the Department of Medical Oncology at AMC and is currently a professor in the Department of Hematology/Oncology at Dongguk University Ilsan Hospital, where he treats gastrointestinal and genitourinary cancers. 

This column was originally published in Korea Healthlog, a sister paper of Korea Biomedical Review, on Aug. 16. -- Ed.