Others have combined UFT plus leucovorin with pelvic radiotherapy for
rectal cancer. The group from the M. D. Anderson Cancer Center is
performing a trial in which UFT plus leucovorin is combined with
preoperative radiotherapy for rectal cancer. A group from Spain
has recently reported their experience with UFT plus leucovorin with
pelvic radiotherapy for unresectable or recurrent rectal cancer.
Thirty-five patients received 45 Gy pelvic radiation therapy with UFT
at 300 mg/m²/d plus leucovorin at 30 mg/d. Fifteen of 22
(68%) patients with unresectable cancer were able to have resections,
and there was a complete pathologic response in three cases. Eight of
35 (23%) had grade 3 diarrhea.
That incidence of grade 3 diarrhea is similar to the 24% incidence
reported in the Mayo/NCCTG 86-47-51 study. This suggests that daily
oral UFT plus leucovorin may be at least as active and also as well
tolerated as infusional 5-FU when given during radiation. It should
be recognized that UFT plus leucovorin was given at full recommended
dose as a single agent, in contrast to the protracted infusion of
5-FU, which was given at a dose of 225 mg/m²/d in the Mayo/NCCTG
study. This dose is less than the dose of 250 to 300 mg/m²/d
typically used in protracted venous-infusion fluorouracil without
Oral administration obviates the need for venous access and its
associated complications. These potential advantages must, however,
be weighed against potential disadvantages, such as variable gut
absorption in some patients[23,24] and patient compliance.
Compliance with oral oncology agents has been reported to be
excellent in many[25,26] but not all trials. A survey of 103
chemotherapy-naive patients with newly diagnosed metastatic cancer
found that 89% of patients preferred an oral over an intravenous
regimen, as long as it was equally effective. Reasons cited for
preference included convenience, lack of intravenous access, control
of the treatment environment, and travel issues. Only a minority of
patients, however, would accept an oral regimen with a lower or less
durable response. Some have presumed that an oral chemotherapy
regimen would result in an improved quality of life, but this has not
been studied prospectively.
The current phase I trial of UFT plus leucovorin combined with
postoperative radiation therapy for rectal cancer is continuing.
Other investigators are also performing phase I trials with UFT plus
leucovorin and radiotherapy for other tumor types. The group from the
University of Alabama Medical Center is combining UFT plus
leucovorin with radiotherapy in patients with both resected and
unresected pancreatic cancer.
Previous studies in patients with stage IV colorectal cancer
randomized to UFT versus parenteral 5-FU confirm equal efficacy, with
significantly less mucositis and diarrhea. A potential therapeutic
advantage for UFT plus leucovorin is the apparent reduction in
overlapping toxicities when combined with pelvic radiation. Results
of one completed study suggest that response rates and toxicities of
UFT plus leucovorin are at least comparable to infusional 5-FU when
combined with definitive or preoperative pelvic radiotherapy for
A survey has shown that most cancer patients would prefer an equally
effective oral chemotherapy regimen. An oral fluoropyrimidine regimen
has the potential to mimic the pharmacokinetics of a continuous
infusion. UFT plus leucovorin is an attractive alternative to either
bolus or continuous-infusion 5-FU combined with postoperative pelvic
radiotherapy for rectal cancer. Accrual to this study is ongoing.
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