Combined Use of Multi-Day Doses of Palonosetron and Aprepitant With Low Doses Dexamethasone in Prevention of Nausea and Emesis Among Patients With Multiple Myeloma and Lymphoma Undergoing Autologous Stem Cell Transplant: A Pilot Study
The use of high doses of chemotherapy and autologous stem cell transplant has been shown to
prolong disease control among patients with multiple myeloma and patients with lymphomas
that have relapsed or recurred. Patients who receive autologous stem cell transplants have
their own stem cells collected and stored prior to receiving high-dose chemotherapy, the
stem cells are then given back to the patient as a transplant. However, the use of high
doses of chemotherapy is associated with significant side effects of nausea and vomiting.
Before the use of newer medications, the incidence of nausea and vomiting could be as high
Nausea is an unpleasant feeling and awareness of the urge to vomit. Vomiting is the process
of throwing up forcefully the contents of the stomach. Retching is an act similar to
vomiting but do not produce throwing up of the contents of the stomach. It is also called
There are three kinds of nausea and vomiting associated with chemotherapy. Acute nausea
and/or vomiting occur within the first 24 hours after administration of chemotherapy.
Delayed nausea and/or vomiting begins after the first 24 hours of chemotherapy and could
last for several days afterwards. Anticipatory nausea/vomiting is experienced prior to
administration of the subsequent chemotherapy.
Chemotherapy produces nausea and vomiting by damaging the cells lining the stomach and
intestines which results in the release a substance called serotonin. The serotonin binds
to a protein or "receptor" (5-HT3 receptor) in the lining of the intestines. The receptors
then send a message to the vomiting center in the brain. The brain then sends signals to
the body to produce nausea and vomiting.
Another substance, called substance P, is also released from the lining of the stomach and
intestines with damage by chemotherapy, and is released together with serotonin. The
substance P binds to another protein called "neurokinin-1 receptor" or NK-1 receptor. These
proteins are found in the intestines and another portion of the brain called "tractus
solitarius". The brain then signals the body to produce nausea and vomiting.
The stimulation of the serotonin proteins results in acute nausea and vomiting. The
stimulation of the NK-1 protein results in delayed nausea and vomiting.
There are medications that could block the serotonin and NK-1 proteins. Serotonin blockers
such as ondansetron or Zofran® are now considered the medications of choice to prevent and
treat nausea and vomiting in the transplant setting. However, their use could still result
in nausea and vomiting in up to 40-50% of patients.
Nausea and vomiting negatively impacts the quality of life of patients undergoing stem cell
transplant for their multiple myeloma and lymphoma. It can affect their appetite and sleep;
and can interfere with activity, social life and enjoyment of life. Therefore, it is
important to find better ways to prevent and control nausea and vomiting associated with
There are two new medications that are available for patients who receive regular doses of
chemotherapy. One is the long acting preparation of the serotonin blocker called
palonosetron or Aloxi®. It is used to control both acute and delayed nausea and vomiting.
Another medication could block the NK-1 receptor, and is called aprepitant or Emend®. This
prevents delayed nausea and vomiting.
Although these two medications are tested and proven to be effective among patients who
receive regular doses of chemotherapy, they have not been tested in combination among
patients who undergo high doses of chemotherapy in the setting of autologous stem cell
The purpose of this study is to evaluate if the combination of these two medications,
together with small doses of steroids (dexamethasone), would be effective in preventing both
acute and delayed vomiting associated with high doses of chemotherapy and stem cell
transplant for patients with multiple myeloma and lymphoma. The usual way to administer
palonosetron is by single injection in the vein before chemotherapy. This is shown to be
effective for chemotherapy given for 1 day. Since chemotherapy regimen for transplant
requires multiple days of treatment, palonosetron will also be administered on multiple days
thereby delivering higher doses of this drug. Aprepitant would be administered at standard
doses. This study would assess if combining palonosetron and aprepitant as well as giving
multiple and higher doses of palonosetron would be safe and effective in the control of
nausea and vomiting in the setting of transplant. The study would evaluate the effect of
combined palonosetron and aprepitant on the quality of life with regards to nausea and
vomiting, of patients undergoing transplant.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
To determine the efficacy and assess the antiemetic response of the combination of Aprepitant and Palonosetron with Prochlorperazine, Lorazepam and low doses of Dexamethasone in achieving complete control from vomiting and nausea among hematopoietic stem
24 hours, Day 3, Day 7
Omar Aljitawi, MD
University of Kansas
United States: Institutional Review Board
|University of Kansas Medical Center||Kansas City, Kansas 66160-7353|