OTTAWA, CANADA-For older and less fit cancer patients, who are more likely to experience greater toxicity but less benefit from combination chemotherapy, a more reasonable alternative might be single-agent and reduced-dose chemotherapy. That was the rationale behind a Canadian phase I/II trial to assess reduced-dose capecitabine(Drug information on capecitabine) (Xeloda) as part of a sequential single-agent therapy for older and less fit patients with advanced colorectal cancer (abstract 3577). The data were presented by M. C. Cripps, MD, of the Ottawa Regional Cancer Center. Results showed an overall median survival of 14.8 months and a "respectable 19.7 month median survival in older patients" with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, the investigators reported. This finding "suggests sequential single-agent therapy beginning with capecitabine may be a reasonable and well-tolerated alternative to combination chemotherapy," the investigators concluded. Five Overlapping Subgroups The multicenter trial was designed to test reduced-dose capecitabine in a population of adults with advanced colorectal cancer "clearly shown not to derive survival benefit from combination chemotherapy." Study participants could have undergone no prior chemotherapy for metastatic disease, and adjuvant fluorouracil(Drug information on fluorouracil) therapy must have been completed 6 or more months before study enrollment. The male/female ratio for the 221 patients accrued was 142/79, or 64%/ 36%. Patients fell into one or more of the following five subgroups at baseline:
- Age ≥ 65 years (173 patients [78%])
- ECOG PS ≥ 1 (145 patients [66%])
- Liver enzyme abnormalities (5 patients [2%]).
- Prior pelvic radiation therapy (54 patients [24%])
- Liver enzyme abnormalities (5 patients [2%]).
Capecitabine was administered at
1,000 mg/m2 twice daily on days 1 to
14 every 21 days. The median number
of cycles was five. Prior pelvic radiation
therapy required dose reduction
to 750 mg/m2 twice daily due to diarrhea
in the third cycle.
Factors Predicting Survival
Among the 191 evaluable patients,
the overall response rate (complete
plus partial responses) was 19%, and
the disease control rate (overall response
plus stable disease) was 81%.
Disease control rates were somewhat
lower for those patients with poorer
ECOG PS, an elevated LDH level, and
higher doses of pelvic radiation therapy
(see Table 1).
The median disease progressionfree
survival was 5.2 months (95%
confidence interval [CI], 4.5-6.9). The
overall median survival at the time of
this report was 14.8 months (95% CI,
11.8-17.0). At median follow-up of
11.1 months, 82 patients were still alive.
Factors predicting shorter survival
were poor ECOG PS and elevated LDH
level. Although the median survival
time for patients with an ECOG PS of
0 was 19.7 months, it fell to 13.2 months
for patients with an ECOG PS of 1 and
6.8 months for patients with an ECOG
PS of 2.
Grade 3/4 Adverse Events
Of the 213 patients evaluable for
toxicity, 23 had grade 3/4 adverse
events. The two most common adverse
events were hand-foot syn
drome,
experienced by eight patients,
and diarrhea, experienced by seven.
Other Canadian institutions participating
in the trial were the London
Regional Cancer Centre, British Columbia
Community Oncology Associates
in Vancouver, the British Columbia
Cancer Agency in Kelowna,
the Windsor Regional Cancer Centre,
the Kingston Regional Cancer Centre,
and the Grand River Regional Cancer
Centre in Kitchener.
