LOS ANGELES--Raltitrexed (Tomudex), a folate-based specific inhibitor
of thymidylate synthase, has been shown in phase III trials to
produce response rates similar to those of the Mayo regimen of
5-fluorouracil (5-FU) and leucovorin in patients with advanced
When response rates are similar, patient preferences concerning
toxicity and chemotherapy administration become increasingly
important, Annie Young, RGN, said at an ASCO poster session.
Ms. Young, of the CRC Institute for Cancer Studies, University of
Birmingham, England, noted that the Mayo regimen requires clinic
attendance for 5 consecutive days every 4 weeks for a bolus
injection. The raltitrexed regimen calls for clinic attendance once
every 3 weeks for a 15-minute infusion.
In the earlier studies, patients receiving the raltitrexed regimen
reported less hair loss, sore mouth, and diarrhea than those on the
Mayo regimen, but more asthenia, nausea, vomiting, and fever.
To determine a possible patient preference regarding the scheduling
or side effects profiles of these regimens, Ms. Young and her
colleagues interviewed 82 patients currently receiving or about to
receive chemotherapy for advanced colorectal cancer. They were asked
to report the degree to which they would find likely side effects and
regimens "upsetting," using a visual analog scale.
When side effect and administration attributes were combined into an
overall profile, 91% of patients selected the profile of the
raltitrexed regimen (P < .001). Mucositis was considered the most
"upsetting" side effect and asthenia the least.
The investigators concluded that patient preferences, when palliative
benefits are similar, should provide an important criterion in the
selection of chemotherapy.
After preclinical studies indicated synergy for the combination of
5-FU and raltitrexed, A. Harstrick, MD, and his colleagues at the
West German Cancer Center, Essen, launched a phase I-II protocol
combining raltitrexed given every 3 weeks with a weekly 24-hour
infusion of 5-FU.
Full Doses of Both Drugs
"What is important here is that we combined two classes of
thymidylate synthase inhibitors and found that we could give almost
full doses of both drugs, 2.4 g/m² of 5-FU weekly for 5 weeks
and and 2.6 mg/m² of raltitrexed every 3 weeks, without
unexpected toxicity," Dr. Harstrick said at his poster
He reported that with 16 of 25 advanced colorectal cancer patients
currently evaluable, there have been 8 partial responses, with the
remaining patients showing disease stabilization or minor
regressions. The group is planning a 50-patient trial with this regimen.