Steven Grunberg, one of the pioneer clinical investigators in
the development of modern antiemetics, describes various approaches to the
management of this important complication of cytotoxic chemotherapy. Dr.
Grunberg describes the use of phenothiazines and antidopaminergic agents as
antiemetics, the discovery that steroids could serve as effective adjuvant
antiemetic agents, and the development of the serotonin (5-HT3)-receptor
antagonists. Thus, we have compazine, metoclopromide, decadron, and a set of
5-HT3 antagonistsondansetron (Zofran), dolasetron (Anzemet), and granisetron
(Kytril)in our therapeutic armamentarium.
For patients, their prejudices about chemotherapy and emesis, which were
identified in Alan Coates’ 1983 study cited in the Grunberg paper, remain
vivid. Most patients whom I advise are relieved that disabling nausea or
vomiting is a complication of the past. In modern outpatient practice, barriers
to the delivery of effective antiemetic therapy, whether pharmacologic, medical,
or reimbursement-related, are surmountable. We have made remarkable progress in
the almost 20 years of research in this field.
Limitations of Antiemetic Therapy
Nevertheless, several difficulties remain. Both anticipatory nausea/vomiting
and delayed emesisie, with onset more than 24 hours after chemotherapy, out
of the range the 5-HT3 blockerscontinue to be clinical problems, as is the
occasional case of idiosyncratic, refractory chemotherapy-induced emesis.
In dealing with anticipatory nausea and vomiting, I have found a chemotherapy
holiday, a change of setting (ie, temporarily moving from the outpatient to the
inpatient setting, or moving to a different outpatient venue), and sedation or
use of antianxiety agents to be occasionally helpful. Delayed emesis is
refractory to the 5HT-3 antagonists, and it is a waste of time, money, and
energy to try them in this setting. Anxiolytics and sedatives can sometimes be
useful, as can the cannabinoids (administered either orally as dronabinol [Marinol]
or inhaled as marijuana). Dr. Grunberg describes several new approaches to the
vexing problem of delayed emesisapproaches that are likely to be useful for
refractory nausea and vomiting, as well as for anticipatory emesis.
Many antiemetic agents are available in intravenous, oral, and suppository
form. From both a medical and fiscal perspective, it is useful that different
delivery forms are available. Some nauseated patients may have difficulty
keeping an oral drug down, and some patients may not have access to third-party
reimbursement for orally or intravenously administered drugs.