Vincent MD, et al. – Experts presented a phase I/II trial of dose–reduced capecitabine in elderly patients with advanced colorectal cancer. With only a small trade–off in efficacy, seen as a lower objective response rate, toxicity was less with dose–reduced capecitabine than with historical full–dose capecitabine. They reported that the improved tolerability could lead to an increased number of cycles of therapy. In addition, progression–free survival (PFS) appeared to be consistently higher at the lower dose.

Methods

• They performed a multicentre phase I/II trial of reduced-dose capecitabine (2000 mg/m2, days 1–14 every 21 days) in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54).
• Patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily, based on phase I results.
• They wanted to determine efficacy in a design that was unlikely to cause high levels of toxicity.

Results

• As per observations, median age in the patient cohort was 72 years.
• They administered a median of 5 and a mean of 8 capecitabine cycles (range: 0–50 cycles).
• This study reported grade 3 or 4 toxicity in 25% of patients during the first 3 cycles (8.1% hand–foot syndrome, 7.7% diarrhea).
• With a 69.7% disease control rate, the response rate was 13.6%.
• In addition, median progression-free survival (pfs) was 5.6 months.
• 56 patients received further capecitabine monotherapy (median of 4 additional cycles), post progression.
• Results reported that median overall survival duration for the patients was 14.3 months.
• They observed significantly higher median survival for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh).