Page 1666 - Hematology_ Basic Principles and Practice ( PDFDrive )

1484 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

THERAPY included cyclophosphamide, methotrexate, or doxorubicin showed
significant efficacy and the superiority of ondansetron over placebo.
Antiemetic Ondansetron also demonstrates efficacy in patients with emesis
(induced by non–cisplatin-containing chemotherapy) that has been
A number of effective antiemetic therapies are used to prevent the refractory to standard antiemetics, with complete control achieved in
nausea and vomiting induced in patients by treatment of their 50% of these patients. When dexamethasone is added, the rate of
hematologic disorders with chemotherapy or radiation therapy. These control is as high as 91%.
antiemetic therapies markedly improve patients’ quality of life. The Ondansetron effectively prevents nausea and vomiting in patients
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vast majority of patients can expect complete control of vomiting, treated with highly emetogenic agents for acute leukemia or multiple
and most patients also are free of nausea. myeloma (i.e., high-dose melphalan) or who are being prepared for
Most studies of the potent antiemetic agents have been conducted bone marrow transplantation with cyclophosphamide and total-body
in patients receiving therapy with cisplatin, a drug of high emetic irradiation. 71,72 In the transplantation recipients, 83% of patient-days
potential. Although cisplatin is not generally used to treat patients were without any vomiting or retching, and in another 10%, there
with hematologic malignancies, the data are included in the following were no more than two emetic episodes. Ondansetron is also effective
discussion because the findings can be extrapolated to other drugs of in preventing emesis induced by single- or multiple-fraction radiation
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equivalent or less emetogenic potential. When available, data regard- therapy. Ondansetron is as effective as high-dose metoclopramide in
ing efficacy in patients receiving radiation therapy or emetogenic preventing nausea induced by cisplatin, cyclophosphamide alone, or
drugs commonly used to treat hematologic disorders are reviewed. doxorubicin chemotherapy.
The choice of antiemetic agents depends on the emetogenic potential Oral granisetron has shown equivalence to ondansetron in studies
of the chemotherapy or radiation therapy regimen, the side effect of patients receiving cisplatin- or carboplatin-based regimens. In
profiles of the antiemetic agents, and patient preferences and patients receiving moderately emetogenic therapy, oral granisetron
characteristics. with dexamethasone was as effective as intravenous ondansetron and
The emetogenic potentials of commonly used chemotherapeutic dexamethasone. Oral or intravenous granisetron and dexamethasone
agents are outlined in the NCCN Clinical Practice Guidelines in were effective in a bone marrow transplantation program in which
Oncology Antiemesis Guideline (www.nccn.org). For patients being patients were treated with Cytoxan and total-body irradiation, and
treated with chemotherapeutic agents with low or minimal emeto- these agents, along with oral prochlorperazine, were also effective in
genic potential, no antiemetic therapy may be needed, or a single patients undergoing peripheral blood SCT for which patients received
agent such as dexamethasone or metoclopramide may be sufficient. Cytoxan, VP-16 or thiotepa, and cisplatin.
For drugs with higher emetogenic potential, standard antiemetic Palonosetron is a second-generation 5-HT3 RA with higher
treatment usually includes combinations of several antiemetic agents potency, stronger receptor-binding activity, and longer half-life than
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along with agents designed to treat anxiety. the other drugs in this class. Palonosetron 0.25 mg intravenously has
been studied in moderately and highly emetogenic chemotherapy.
Several subgroup analyses of the registrational noninferiority trials
Combination Antiemetic have been reported in which palonosetron was superior. Palonosetron
has been identified as the preferred 5-HT3 RA in prevention of
These combinations include a 5-HT3 RA such as ondansetron and nausea and vomiting from moderately emetogenic regimens. Ondan-
a corticosteroid such as dexamethasone for moderately emetogenic setron and the other 5-HT3 RAs have far fewer side effects than
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regimens. For highly emetogenic combination chemotherapy or high-dose metoclopramide. Reports of extrapyramidal reactions are
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regimens that include two moderately emetogenic agents, such as rare, and sedation, dystonic reactions, akathisia (e.g., severe restless-
cyclophosphamide and adriamycin, an NK-1 inhibitor such as apre- ness, “ants-in-the-pants” feeling), and tardive dyskinesias do not
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pitant should be added to the antiemetic combination. Optional occur. Patients can develop constipation, mild headache, QT prolon-
lorazepam may be added for anxiety-related symptoms. It is impor- gation, and elevated levels of transaminases.
tant to give antiemetic therapy before administering chemotherapy
agents and to continue for about 24–72 hours after the drugs have Corticosteroids
been given to prevent emesis. Patient-specific factors and prefer- The mechanism of the antiemetic action of corticosteroids remains
ences regarding degree of alertness can help the health care provider undefined. Corticosteroids are effective when used alone to prevent
choose an antiemetic regimen, as can the level of anxiety the provider emesis induced by agents of moderate or low emetogenic poten-
observes in the patient. For instance, younger patients have a higher tial. 71,72 They are also a useful component of antiemetic therapy regi-
incidence of CINV and of metoclopramide-related acute dystonic mens that include ondansetron, granisetron, aprepitant, or
reactions; trismus or torticollis was seen in only 2% of patients older metoclopramide and add efficacy in randomized controlled trials. 71,72
than 30 years of age but in 27% of younger patients. Therefore The recommended specific corticosteroid drug, dose, and dura-
even if they are receiving only moderately emetogenic therapy, they tion of therapy has not been determined. Dexamethasone and
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may require an antiemetic regimen for high-emetogenic drugs. methylprednisolone are the best-studied agents, but no trials have
Younger patients find cannabinoids (e.g., Marinol) more effective demonstrated the superiority of one corticosteroid over another.
than do older patients because they can better tolerate the side effects Using anecdotal evidence recommendations for dexamethasone
associated with the therapeutic doses of these agents. Elderly patients 4-8 mg orally (PO) two to three times per day, methylprednisolone
also have high risks of extrapyramidal side effects and are more 16–32 mg PO two to three times per day, or prednisone 20–30 mg
susceptible to anticholinergic and sedating side effects. 5-HT3 RAs PO two to three times per day have all been suggested.
are therefore preferred to regimens containing metoclopramide and
diphenhydramine. Metoclopramide
The antiemetic evidence behind the utilization of different medica- Metoclopramide is a substituted benzamide that promotes gastric
tions changes over time. We recommend utilizing the ASCO clinical motility and reduces the emetic activity of chemotherapy agents by
practice guidelines for recommendations on combination antiemetic blocking dopamine receptors (at low-to-moderate doses) and 5-HT3
regimens: http://www.instituteforquality.org/practice-guidelines. receptors (at high doses) in the chemoreceptor trigger zone. Because
of a more favorable side effect profile, 5-HT3 antagonists have
Serotonin Receptor Antagonists: Ondansetron, replaced high-dose metoclopramide. At lower doses (5–10 mg orally
Granisetron, and Palonosetron or intravenously every 6 hours) metoclopramide is useful in treating
Ondansetron, granisetron, and palonosetron are the best studied of mild-to-moderate and delayed nausea and vomiting. Delivery of the
the 5-HT3 RAs. This class also includes the drugs dolasetron and drug on a schedule that maintains adequate levels during expected
tropisetron. Several studies of patients receiving regimens that emesis appears to be important.