MILAN, Italy-A reduced dose
of oral capecitabine (Xeloda) is a welltolerated,
effective, and convenient treatment
for elderly patients with advanced
These results of an Italian study were
reported by one of the investigators, Laura
Catena, MD, Istituto Nazionale per lo
Studio e la Cura dei Tumori, Milan, Italy
(ASCO abstract 3050).
"There is a need for a well-tolerated
and effective treatment in elderly breast
cancer patients. Half of all breast cancers
are in elderly women, and many treatments
for advanced breast cancer are
poorly tolerated by elderly patients," Dr.
"Oral capecitabine enables convenient,
outpatient treatment. It achieves consistently
high efficacy in metastatic breast
cancer, with a favorable safety profile characterized
by a particularly low incidence
of grade 3/4 adverse events, myelosuppression,
and alopecia." Capecitabine, a
tumor-activated, oral fluoropyrimidine,
generates fluorouracil (5-FU) preferentially
in tumor tissue, and presents good
activity in a wide range of solid tumors.
25% Dose Modification
The open-label, noncomparative,
phase II study was conducted at a single
center between May 1999 and February
2003. The study evaluated the global therapeutic
index of twice-daily oral capecitabine
in elderly patients with locally advanced
metastatic breast cancer.
Patients received oral capecitabine
1,250 mg/m2 bid, days 1 to 14 every 21
days (n = 30). To improve the safety profile,
the protocol was amended to a reduced
dosage of oral capecitabine 1,000
mg/m2 bid, days 1 to 14 every 21 days
(n = 43). This reduction was in response
to new dosing guidelines recommending
a 25% dose reduction in elderly, frail patients
who may be at risk of an increased
incidence of grade 3/4 toxicities.
Patients with a partial response or stable
disease had up to six cycles of treatment;
patients with complete response
had an additional two cycles, and patients
with progressive disease were withdrawn
from the study.
A total of 73 patients were enrolled,
and the median age of the patients was
72.9 years (range 65 to 89). All patients
had measurable or evaluable advanced
disease, Karnofsky performance status
≤ 2, and adequate bone marrow, cardiac,
renal, and hepatic function.
Patients could have had no more than
one prior chemotherapy regimen and/or
two hormonal regimens for metastatic
disease. A previous therapy containing
fluorouracil was allowed but a minimum
period of 12 months was required starting
from the last dosage of the previous treatment.
The metastatic sites were soft tissue
(28), bone (27), liver (26), lung (20), and
others (20). The primary end points were
the safety profile and tolerability, the secondary
end points were response rate and
time to progression.
Most Completed Full Course
Overall, 39 patients (53%) completed
the full course of treatment. There was a
similar incidence of premature withdrawal
at the two treatment doses, and treatment-
related adverse events led to premature
withdrawal of 13 patients (18%).
All patients were evaluable for toxicity
and 62 patients for response. Toxicity
according to National Cancer Institute-
Common Toxicity Criteria (NCI-CTC)
Bethesda guidelines was: grade 3/4 diarrhea
(6%), grade 3 vomiting (7%), grade
1/2 hand-foot syndrome (47% in the
higher-dose group and 30% in the lowdose
group), grade 2/3 asthenia (26%),
grade 2 stomatitis (11%). There were two
deaths during the study; one due to treatment
related diarrhea/dehydration, and
one due to disease progression.
"There were fewer dose reductions for
adverse events required in patients receiving
the lower dose compared with patients
receiving the higher dose," noted the
study's lead investigator, Giuseppe Procopio,
MD, of Istituto Nazionale per lo Studio
e la Cura dei Tumori, Milan, Italy.
"Oral capecitabine demonstrated considerable
activity, achieving a high rate of
disease control, with no significant differences
between the lower and higher dose
groups," Dr. Procopio continued. Disease
control was 86% with the lower dose and
77% with the higher dose (see Table 1).
Objective responses were documented in
36% of patients (26), with 3% complete
remission, 32% with stabilization of
disease, and 18% with progression. The
median time to disease progression was
77 days (range 14-139 days).
Dr. Catena reported that the study
found a favorable safety profile of oral
capecitabine 1,000 mg/m2 twice daily in
elderly patients compared to the higher
dose. "There was a low incidence of grade
3/4 adverse events and no grade 3/4
myelosuppression. There was a lower incidence
of grade 3/4 diarrhea (2% vs 13%)
and fewer dose reductions (2% vs 30%)
compared with oral capecitabine 1,250
mg/m2 twice daily."
This lower dose regimen is as effective
and better tolerated than the higher dose
regimen and can be recommended
for elderly patients with locally
advanced metastatic breast cancer," Dr.