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

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Pharmacy Times, August 2009, Volume 75, Issue 8

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 withPanitumumab

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 withTamoxifen Increase Risk ofBreast 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.