Hope Rugo, MD
Despite progress in treating chemotherapy-induced nausea and vomiting (CINV), especially in the acute phase up to 24 hours after treatment, the condition is still one of the side effects patients fear most, according to Hope S. Rugo, MD, professor of Medicine and director of Breast Oncology and Clinical Trials Evaluation at the Helen Diller Family Comprehensive Cancer Center, based at the University of California, San Francisco.
â€œPatients feel like this is a really big deal,â€ said Rugo, during one of her sessions at the recent Miami Breast Cancer ConferenceÂ®. â€œWeâ€™ve done a remarkable job of controlling vomiting in most patients,â€ she saidâ€”once the most feared complication of chemotherapyâ€” â€œbut weâ€™re still not so great on nausea.â€
Rugo also highlighted progress in controlling acute CINV, whereas delayed CINV (occurring 24 hours to up to 6 days after chemotherapy) remains problematic. â€œMost of our patients receiving AC [doxorubicin and cyclophosphamide]â€“ type regimens have some degree of delayed nausea. We see it a lot with the platinum salts as well, and you can see it with a host of other agents.â€
Currently, the most effective drugs for the prevention and treatment of CINV, Rugo said, are the serotonin/5-HT3 receptor antagonists, the new substance P/neurokinin-1 (NK-1) receptor antagonists, and steroids (Box
). â€œInterestingly, steroids are one of the very important agents that play a critical role in preventing and treating CINV.â€
National Comprehensive Cancer Network (NCCN) Guidelines offer guidance for emesis prevention for patients receiving agents which place them at high, moderate, or low risk for CINV. Rugo, who is a member of the NCCN Panel on the Prevention of Nausea and Vomiting, noted that recent changes to the guidelines indicate palonosetron as preferred, primarily for patients at high risk for emesis, but also for those at moderate risk, because of the drugâ€™s combination of acute and delayed effects.
Three Major Classes of Antiemetic Drugs
5-HT3 Receptor Antagonists
2nd Generation: palonosetron (IV only) Effective for both acute and delayed CINV as a single IV infusion
1st Generation: ondansetron, granisetron (also in transdermal form), dolasetron (PO only) Primarily effective for acute CINV, also for rescue
Aprepritant, fosaprepitant Effective for delayed CINV when given with a 5-HT3 receptor antagonist
Rugo said that itâ€™s also important to tell patients about potential toxicities of agents used to control CINV, so they can take preventive measures. â€œThe 5-HT3 receptor antagonists cause headache in a subset of patients and constipation in almost everybody,â€ she noted, and patients who are at risk for prolonged QT can also be at risk with repeated doses. She added that for the N-1 receptor antagonists, the primary risk is drugâ€“drug interactions, more so with the oral form than IV.
Researchers have looked at how patientsâ€™ actual experiences with CINV match up with physiciansâ€™ and nursesâ€™ predictions and perceptions. â€œThis is a very sobering lesson for all of us,â€ said Rugo. â€œWeâ€™re really good at assessing what our patients think in the acute setting,â€ but when CINV persists for days, â€œour perception generally underrates it, compared with what patients think.â€
Anticipatory emesis can be a big problem as well, said Rugo. â€œGood control in the first cycle significantly reduces anticipatory nausea and emesis,â€ she stressed. â€œUse your best drugs up front.â€ In a young woman who is receiving AC chemotherapy, for example, â€œyou want to pull out all the stops; you can always cut back, but adding more is difficult because of this anticipatory emesis.â€ Additional strategies include relaxation, hypnosis/ guided imagery, music therapy, acupuncture/ acupressure, and alprazolam or lorazepam the night before, and morning of, treatment.
â€œBetter understanding of the mechanisms of action have led us to the development of two very effective new classes of drugs,â€ Rugo concluded, â€œand hopefully this will lead to even better agents in the future.â€