Pharmacy Times

Oncology Pharmacy Highlights from the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting

Author: Christina Loguidice and Christin Melton

Pharmacists Who Supply
Proper Information CanASCO Conference
Improve Treatment Adherence

Pharmacists play an important role in
ensuring that patients given antineoplastic
drugs on an outpatient basis adhere
to treatment. Pharmacists supply the
prescribed drugs and have the opportunity
to educate patients on their proper
use and measures that can be taken to
ameliorate adverse effects and enhance
outcomes. Several large-scale studies
have shown that approximately one
third of patients with cancer do not
take their medications as prescribed.
A recent German study presented at
the 2009 ASCO Annual Meeting sought
to determine whether the failure of
pharmacists to provide patients with
sufficient information might contribute
to their nonadherence.

The study included 312 patients
throughout Germany who were undergoing
cancer treatment and receiving pharmacotherapies
from 1 of 47 pharmacies
participating in the study. Patients completed
a questionnaire that evaluated
their satisfaction with the information
they received at the pharmacy. Analysis
of the questionnaires revealed that in
oncology-focused pharmacies, 50% of
patients received specific counseling,
but only 6% of the other pharmacies
provided oncology-specific information.
In addition, 18% of patients surveyed
would have liked counseling but did
not receive it, compared with 17% who
were not interested in receiving more
information.

The study found that, overall,
patients were disappointed in the
lack of information they received
regarding medication (n = 78), nutrition
(n = 134), supportive therapy
(n = 109), and complementary medicine
(n =159). Researchers concluded
that pharmacists have an opportunity
to improve treatment adherence and
outcomes in patients with cancer by
being proactive in providing information
regarding medication, supportive
therapy, nutrition, and complementary
treatments.

Prophylactic Regimen Reduces Skin Toxicities Associated with
Panitumumab

Final results of the Skin Toxicity Evaluation Protocol with Panitumumab (STEPP) trial
show that prophylactic skin treatment reduces the severity of skin toxicities associated
with panitumumab (Vectibix), an epidermal growth factor receptor (EGFR)
inhibitor used to treat metastatic colorectal cancer (mCRC), by nearly 50%. Skin
toxicity is the most common adverse effect of EGFR inhibitors, and multiple studies
have established a positive correlation between the severity of skin rash and
the drug's effectiveness. Researchers from several US institutions worked together
to develop a skin regimen that might mitigate some of the dermatologic effects of
panitumumab and prevent therapy interruption or discontinuation.

The STEPP trial randomized 48 patients with mCRC to preemptive skin treatment
with moisturizer, sunscreen (minimum sun protection factor of 15), a topical
steroid, and 100 mg doxycycline twice daily. The prophylactic skin regimen was
administered 24 hours before the first dose of panitumumab and continued daily for
6 weeks. The remaining 47 patients in the study received symptom-driven reactive
treatment, initiated only after evidence of skin toxicity.

At the end of the trial, 6 weeks after the first dose of panitumumab, the incidence
of skin toxicities ≥ grade 2 was 23% in the preemptive skin therapy group, compared
with 40% in the reactive group. Patients in the preemptive group also had a better
Dermatology Life Quality Index score than patients in the reactive group.

CYP2D6 Inhibitors Used with
Tamoxifen Increase Risk of
Breast Cancer Recurrence

Women who take tamoxifen for breast
cancer along with certain widely used
antidepressants known to inhibit the
cytochrome P-450 2D6 (CYP2D6) enzyme
have nearly double the rate of cancer
recurrence. CYP2D6 plays a major role
in tamoxifen metabolism. Earlier studies
determined that poor CYP2D6 function
results in lower plasma concentrations
of endoxifen, the active metabolite
of tamoxifen, and reduces the overall
effectiveness of tamoxifen therapy. A
more recent study has found that some
selective serotonin reuptake inhibitors
(SSRIs)-fluoxetine (Prozac), paroxetine
(Paxil), and sertraline (Zoloft)-counter
the activation of tamoxifen via the
CYP2D6 pathway, diminishing its effectiveness.
Weak CYP2D6 inhibitors, such
as citalopram (Celexa), escitalopram
(Lexapro), and fluvoxamine (Luvox), were
not associated with an increased rate of
cancer recurrence.

The retrospective study looked at data
for 1300 women with breast cancer who
initiated treatment with tamoxifen in
2003-2005. Patients were monitored for
a median of 2.7 years and were eligible
for inclusion if they remained at least
70% compliant with their tamoxifen
therapy. For those patients who took
tamoxifen and a CYP2D6 inhibitor (not
necessarily an antidepressant) during
the study period, the average duration of
concurrent use was 340 days.

Initially, researchers stratified the
women into 2 cohorts: those who took
a moderate-to-potent CYP2D6 inhibitor
(n = 353) and those who did not take any
CYP2D6 inhibitors (n = 945). The 27% of
patients who took a CYP2D6 inhibitor
had a recurrence rate of 13.9% at 2-year
follow-up versus 7.5% of women who
took tamoxifen alone.

Approximately 60% of the women on
CYP2D6 inhibitors took an SSRI. Looking
at just this subset of patients, researchers
compared the rate of recurrence for
those on moderate-to-potent CYP2D6
inhibitors (n = 213) versus the rate for
those who took weak CYP2D6 inhibitors
(n = 137). The rate of breast cancer
recurrence was nearly double in the
group that took SSRIs associated with
moderate-to-potent CYP2D6 inhibition:
16% versus 8.8%, respectively.

As many as 500,000 women in the
United States are taking tamoxifen
at any given time, and nearly 30% of
those women also take an antidepressant,
which is often prescribed off-label
for tamoxifen-related hot flashes. An
SSRI that is a weak CYP2D6 inhibitor
or an antidepressant like venlafaxine
(Effexor), which has little to no effect
on CYP2D6, may be a better choice for
these patients.

Oncologists are not always aware
when another physician prescribes an
antidepressant for their patient, and
pharmacists play a major role in ensuring
that women on tamoxifen are not
using any drugs likely to counteract
the effectiveness of their cancer treatment.
The FDA has said it plans to add a
warning to the tamoxifen label, alerting
physicians and patients to the possible
interaction between certain SSRIs and
tamoxifen and the effect of concurrent
use on outcomes.

Vistonuridine: A Life-saving Antidote for 5FU Overdose
Approximately 275,000 patients annually are treated with
5-fluorouracil (5FU), a chemotherapy agent that is typically
administered via an infusion pump at or close to its maximum
tolerated dose (MTD). When the MTD is exceeded, either
because of an error or the patient's inability to clear 5FU efficiently,
serious or life-threatening toxicity can result.

The National Institutes of Health estimates that approximately
3% (8250) of patients annually develop serious toxic
reactions from overexposure to 5FU, and about 1300 die
from it.

Uridine can dilute intracellular fluorouridine nucleotides
derived from 5FU, reducing their ability to become lethal,
but it has poor bioavailability. Wellstat Therapeutics Corp has
developed vistonuridine (the first viable prodrug of uridine), an
orally administered agent that delivers approximately 8-fold
more uridine than administration of uridine itself. Although
vistonuridine is still an investigational drug, its use is permitted
under the emergency-use investigational new drug (IND)
provisions of the FDA.

At the time the study was presented on June 1, 17 patients
had been treated with vistonuridine for 5FU overexposure;
since then, an additional 3 patients have required vistonuridine.
Wellstat was contacted after each overdose, and once
emergency-use INDs were obtained from the FDA, vistonuridine
was immediately flown in or sent by courier to the
patient's clinic. The patients generally received vistonuridine
within 8 to 96 hours after the overdose, and all 20 made a full
recovery.

A severity score that integrated dose and infusion rate was
calculated for each patient and used to predict the expected
toxicity and outcome after overexposure to 5FU. Even though
a fatal outcome would have been expected for 16 patients
based on the dose and rate of 5FU administration, most
patients experienced only relatively mild toxicity. In contrast,
only 2 patients survived out of 13 identified in the literature
as having had similar 5FU overdoses but treated only with
supportive care.

These data support the use of life-saving vistonuridine in the
event of a 5FU overdose. Wellstat said it plans to seek regulatory
approval in the United States and Europe.