Advanced Colorectal Cancer Patients May Prefer Raltitrexed

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 colorectal cancer.

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 presentation.

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.