Despite Progress, Complete Control of Chemotherapy-Induced Nausea Lags Behind Vomiting Control

Control of chemotherapy-induced nausea and vomiting (CINV) has come a long way in the past 30 years. Thirty years ago, about 10% of patients had complete control of emesis; in the 1990s about 50% had complete control. Today about 85% of patients treated with highly emetogenic chemotherapy have complete control of emesis.  Complete control of nausea lags behind vomiting, which is almost universally controllable, said Richard Gralla, MD, Medical Director, Quality of Life Research Associates, New York City.

 

Speaking at the MASCC/ISOO International Symposium on Supportive Care in Cancer, Gralla, the 2012 symposium chair, said, “Our goals are to eliminate nausea and vomiting completely in every patient every time. This is achievable, but we need more science to bring efficacy in clinical trials into effectiveness in medical practice.” Incorporating emesis guidelines into practice can help achieve this goal, and the advent of electronic medical records will facilitate this.

 

Eliminating emesis improves quality of life (QOL) dramatically for patients, he continued. “Patients with complete control of emesis during chemotherapy rank their QOL 3 days after chemotherapy the same as before chemotherapy. If we don’t control emesis, one-third of patients will have a decline in QOL,” he stated. “Nothing else in the immediate period around chemotherapy affects QOL as much.”

 

By 1982, high-dose metoclopromide was found to protect >40% of  cisplatin-treated patients from emesis. The next year, metoclopromide plus dexamethasone achieved 60% complete control of emesis, Gralla continued.

 

“By 1990, we could control about 50% of patients receiving nasty drugs with high-dose metoclopromide plus steroids,” he stated. “We discovered that higher doses of metoclopromide were needed to make it an effective 5-HT3 [serotonin] antagonist.”

 

The search continued for new drugs. In the 1990s, granisetron, ondansetron, and dolasetron were found to achieve similar rates of complete emesis control of about 79%, upping the ante even further.

 

In 2000, a study by Aapro et al showed that giving granisetron plus dexamethasone or either drug alone on the first day of chemotherapy reduced the occurrence of delayed emesis. “This suggests that if we give dexamethasone on day 1, we may not have to give it later,” Gralla said.

 

“There was a modest change in efficacy from 1990 to 2000, but a huge impact on effectiveness. We achieved 60% complete control of emesis with dexamethasone–an easy agent that has few side effects and can be given once a day. Every oncology unit can use this. We now help millions of patients instead of thousands,” he commented.

 

Palonosetron, a drug with higher affinity to the 5-HT3 receptor, was the next entrant. Palonosetron plus dexamethasone achieved similar acute control of emesis as granisetron plus dexamethasone but improved the effect on delayed emesis, Gralla said.  

 

Aprepitant, a newer drug, is the only antiemetic targeted to the neurokinin 1 (NK1) pathway involved in emesis. Other NK1 blockers are under study. Studies have shown that adding aprepitant to ondansetron plus dexamethasone improved control of delayed emesis, he noted.

 

“Patients need protection during every cycle of chemotherapy. The three-drug regimen was better and was even more superior over time,” Gralla said.

 

“We have achieved nearly 100% complete control of vomiting. Nausea is still a miserable problem for our patients. We need novel trial designs and new agents. We may need to target different receptors,” Gralla said.

 

The best way to treat CINV is by following evidence-based guidelines, not economically based or opinion-based guidelines, he emphasized.

 

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