MEXICO CITY-In patients
with metastatic breast cancer, capecitabine
(Xeloda) monotherapy followed by
taxane monotherapy offers greater benefits
in social functioning than capecitabine/
taxane concurrent therapy. In some
patients, sequential therapy with capecitabine
administered before taxanes may
therefore be a more appropriate treatment
strategy than capecitabine/docetaxel
(Taxotere) or capecitabine/paclitaxel
combination therapy after anthracycline
failure.
These early results from a quality of
life (QOL) study conducted by the Mexican
Oncology Study Group were reported
by Laura Torrecillas, MD, medical oncologist
and head of the chemotherapy service
at the 20 Noviembre ISSSTE Medical
Center in Mexico (ASCO abstract 3011).
At the interim analysis, the phase III ongoing
trial shows a similar disease control
rate and a slightly inferior toxicity profile
with capecitabine alone followed by taxane,
compared with the combination of
capecitabine and docetaxel or paclitaxel.
This study looked at whether sequential
monotherapy could improve QOL more
than a first-line combined approach.
Preliminary Data Focus
on Capecitabine Monotherapy
"In these preliminary data, few of the
patients in the sequential arm have received
taxane therapy, and therefore the
results are more representative of capecitabine
monotherapy than sequential
capecitabine monotherapy followed at
progression by taxane monotherapy.
However, mature results will provide a
clearer indication of any differences between
these two treatment strategies" Dr.
Torrecillas noted.
In describing the rationale for the phase
III study, the investigators pointed out
that capecitabine monotherapy has demonstrated
consistently high efficacy and a
favorable safety profile in patients with
metastatic breast cancer who have been
pretreated either with anthracyclines or
with a combination of anthracyclines and
taxanes. Capecitabine is an oral, fluoropyrimidine
carbamate that generates fluorouracil
(5-FU) preferentially in tumor
tissue through exploitation of high intratumoral
concentrations of thymidine
phosphorylase (TP).
The oral administration and good tolerability
of capecitabine offer improved
patient convenience, which would potentially enhance patient QOL. From one
perspective, the high single-agent activity
of capecitabine, and the lack of overlapping
toxicity profiles with taxanes, in addition
to their synergistic activity due to
TP upregulation in tumor tissue, suggest
that they are most effectively administered
in combination.
However, sequential therapy with
capecitabine administered as monotherapy
followed by taxanes at disease progression
has the potential to provide additional
QOL benefits compared with
combination therapy from the outset, assuming
that efficacy for cancer control is
satisfactory.
Three Treatment Arms
The study compared three treatment
arms:
-
capecitabine monotherapy 1,250
mg/m2 twice daily, days 1 to 14, followed
by docetaxel or paclitaxel after progression
(58 patients) vs -
capecitabine/paclitaxel combination
therapy, with capecitabine 825
mg/m2 twice daily, days 1 to 14, plus paclitaxel
175 mg/m2 day 1 (66 patients) vs -
capecitabine/docetaxel combination
therapy, with capecitabine 825
mg/m2 twice daily, days 1 to 14 plus docetaxel
75 mg/m2 day 1 (69 patients).
The treatment is continued until disease
progression or unacceptable toxicity.
Side effects are managed by treatment
interruption or dose reduction.
The investigators report that the baseline
characteristics were generally well
balanced in the three groups. To be eligible
for the study, patients were required
to have measurable metastatic breast cancer,
be between 18 and 75 years old, have
a Karnofsky performance status ≥ 50, have
a life expectancy greater than 3 months,
and one prior anthracycline-based chemotherapy
regimen. Prior adjuvant therapy
with cyclophosphamide, methotrexate,
fluorouracil (CMF) was also
permitted. Patients could not have had
hormonal therapy less than 30 days prior
to enrollment.
Questionnaire Assesses Trends
QOL was assessed using the European
Organization for Research and Treatment
of Cancer QLQ-C30 v2.0. The questionnaire
is completed at baseline and at 3-
week intervals (always before each treatment
cycle) until week 48, and at the end
of the study.
More than 80% of patients completed
at least one QOL questionnaire after the
start of the study and were therefore evaluable
for the QOL outcome. Substantially
more questionnaires were completed at
the end of the study in the capecitabine/
docetaxel arm compared with the other
two study arms.
The global health status was similar in
all three treatment arms. "No consistent
or sustained trends have been observed in
global health status during the study period,"
Dr. Torrecillas reported. "At cycle eight, global health status is significantly
improved with capecitabine/paclitaxel
compared with the other two arms, but
there are no significant differences between
treatment arms at the end of the
study."
Social functioning was significantly
improved with capecitabine monotherapy
followed by taxane monotherapy compared
with the other two study arms.
"This is possibly due to the oral administration
route and favorable tolerability
(including lack of hair loss) associated
with taxane monotherapy," Dr. Torrecillas
explained.
"Further data are required to improve
the robustness of the results," Dr. Torrecillas
noted. "In addition, inclusion of
data after administration of taxane
therapy in the sequential arm will provide
a more accurate representation of sequential
therapy rather than the currently
available data for the single-agent
capecitabine."