BANGOR, United Kingdom-
The possibility exists of developing an
all-oral regimen for advanced breast cancer
that is both effective and well tolerated.
In progressing toward that objective,
investigators conducting a phase II study
(ASCO abstract 183) report that a combination
of intravenous vinorelbine (Navelbine)
and oral capecitabine (Xeloda)
demonstrated good activity in advanced
breast cancer patients who had been previously
treated with anthracycline or anthracenedione.
"The possibility of developing an alloral
regimen is attractive," noted Nicholas
Stuart, MD, School of Biological Sciences,
University of Bangor, United
Kingdom. "The ideal chemotherapy regimen
for metastatic breast cancer is effective,
well tolerated and convenient. New
agents need to be evaluated with this
ideal in mind. Oral chemotherapy is an
attractive option for many patients, especially
due to its convenience."
Dr. Stuart reported at last year's American
Society of Clinical Oncology meeting
that the combination of vinorelbine
and fluorouracil given by continuous infusion
is active and well tolerated. "We
aimed to develop a regimen that would be
tolerable and equally effective after an
anthracycline and/or a taxane, and would
avoid the problems of continuous infusion,"
Dr. Stuart said.
"This current study is the next step
towards creating such a chemotherapy
regimen. In particular, the regimen appears
effective even in women who have
already received the two most active drugs
in breast cancer-doxorubicin and a taxane,
such as paclitaxel. To this end, we
evaluated the tolerability and effectiveness of the combination of capecitabine
Study Design and
The regimen in the study consisted of
capecitabine 1,000 mg/m2 twice daily for
14 days each 21-day cycle, and vinorelbine
25 mg/m2 IV (max 60 mg) days 1 and
8 each 21 day cycle. Treatment continued
until disease progression, unacceptable
toxicity, patient request, or to a maximum
of eight cycles.
To be eligible for the study, patients
were required to have histologically or
cytologically confirmed female breast cancer;
progressive, locally advanced, or metastatic
disease; previous chemotherapy
with anthracycline or anthracenedione;
one or two previous chemotherapy regimens;
an Eastern Cooperative Oncology
Group (ECOG) Performance Status of 0
to 2; and normal full blood count, liver
function, and renal function. Excluded
were patients with previous irradiation
therapy to measurable disease sites, pre
vious treatment with vinorelbine or
capecitabine, uncontrolled hypercalcemia
or central nervous system metastases, or
clinically significant cardiac disease.
Eighty-five patients were enrolled in
the study and data are available on 58
patients. The median age is 56 years (range
27-80). Of these 58 patients, 46 had prior
treatment with anthracycline, and 35 had
prior treatment with adjuvant anthracycline.
Thirteen patients had prior taxane
Median Achieved Doses
The median achieved dose of vinorelbine
was 42 mg/m2/3 weeks, which was
84% of the intended dose. The median
dose of capecitabine over 3 weeks was
1,051 mg/m2, 79% of the intended dose.
Fifty-three percent of treatments were
delayed, the primary cause being neutropenia.
Grade 3/4 toxicities include nausea/
vomiting (6%), peripheral neuropathy
(5%), diarrhea (2%), constipation (1%),
and hand-foot syndrome (1%). There
were no treatment-related deaths.
The overall response rate (n = 40) was
43%, with 3% complete response and
40% partial response. In addition, 15%
had stable disease, 35% progressive disease,
and 8% were not assessed because of
early cessation of treatment due to patient
request or death.
"Vinorelbine and capecitabine in combination
is an active regimen, and the
activity is comparable to that reported
with vinorelbine and fluorouracil (43%
and 50% response rates, respectively),"
Dr. Stuart summarized. "The regimen is
active after prior treatment with anthracyclines.
Vinorelbine and capecitabine
combination therapy is generally well tolerated,
with neutropenia from vinorelbine being common but rarely severe."
The Next Study
Dr. Stuart's next phase II study will
assess the oral formulation of vinorelbine
in combination with capecitabine. The
prospect of oral vinorelbine raises the
possibility of a highly active all-oral regimen
for metastatic breast cancer. "The
aim is to devise a regimen that can be
given all orally and still be just as effective,"
Dr. Stuart said. "The recent introduction
of oral vinorelbine allows this
possibility to be tested. A similar study
combining oral vinorelbine with oral
capecitabine is due to start later this year.
The possibility exists that an effective,
well tolerated, and convenient oral regimen
for advanced breast cancer can be