CHICAGO-As first-line treatment
for metastatic colorectal cancer,
XELOX, the combination of oral capecitabine
(Xeloda) plus oxaliplatin (Eloxatin),
is safe and effective. These mature
results of a multinational trial (ASCO abstract
1023) were reported by Professor
Eric Van Cutsem, MD, PhD, senior academic
staff member at University Hospital-
Gasthuisberg, Leuven, Belgium.
Dr. Van Cutsem noted that a significant
feature of capecitabine is the substantially
improved convenience that it
offers compared with infusional 5-FU.
XELOX requires only one clinic visit every
3 weeks, simplifying therapy and allowing
the patient to lead a more normal
According to Dr. Van Cutsem, "tumor-
activated capecitabine was designed
to mimic infused 5-FU, and with advantages
in convenience and patient preference,
capecitabine should also replace
5-FU/leucovorin in combination."
High Response Rates
Patients in the phase II trial received a
2-hour infusion of oxaliplatin 130 mg/m2
on day 1, and oral capecitabine 1,000
mg/m2 bid on days 1 to 15, followed by 7
days off. The treatment continued for 11
cycles in patients with tumor response or
stable disease, and the median number of
cycles was 9.
After a minimum follow-up of 24
months, XELOX achieved an overall response
rate of 55%. "The high response
rate was maintained, with all subgroups
achieving a rate of 50% or higher," according
to one of the co-investigators,
Christopher Twelves, MD, University of
Leeds and Bradford, United Kingdom. In
comparison, earlier studies by de Gramont
and Goldberg combining 5-FU and
oxaliplatin showed an overall response
rate of 50% and 38%, respectively.
In the XELOX study, the median progression-
free survival was 7.7 months and
the median overall survival was 19.5
months. The 1-year survival rate was 71%.
The study included 96 patients with
metastatic colorectal cancer. Patients
ranged in age from 34 years to 79 years,
with a median age of 64 years. Eligible
patients had measurable metastatic colorectal
cancer, a Karnofsky performance
status greater than 70, a life expectancy of
at least 3 months, no prior therapy with
oxaliplatin, capecitabine, or irinotecan
(CPT-11, Camptosar), and no prior adjuvant
therapy within 6 months of enrollment.
Disease characteristics of the patients
were typical of a first-line metastatic colorectal
cancer trial: 64% colon tumors,
33% rectal tumors, and 3% rectosigmoid
tumors. More than half of the patients
(54%) had more than one metastatic site.
Lung metastases were present in 32% of
patients and liver metastases in 77%.
Twenty-seven percent of patients had received
prior adjuvant treatment.
Capecitabine and oxaliplatin do not
overlap in key toxicities. The safety data
were consistent with prior studies with
XELOX, and compare favorably with the
safety profile of FOLFOX4 (fluorouracil,
Overall, there was a low incidence of
grade 3/4 treatment-related adverse
events, and only three patients experienced
grade 3 hand-foot syndrome. The
most common grade 3/4 treatment-related
adverse events were sensory neuropathy
(17%), diarrhea (16%), and nausea/
Receive Full Dose
Of particular importance was the fact
that 50% of patients received full dose
capecitabine/oxaliplatin throughout their
treatment-an impressive percentage given
the long duration of the treatment.
"XELOX has comparable efficacy and
safety to the FOLFOX regimens in firstline
treatment of metastatic colorectal
cancer, being highly active and safe, while
requiring far less time of the patient." Dr.
Van Cutsem concluded,
Ongoing phase III trials are evaluating
XELOX and comparing it to FOLFOX.
The objective of these studies is to verify
the ability of capecitabine to replace
5-FU/leucovorin as the backbone of advanced
colorectal cancer therapy.