TEGAFOX Could Replace FOLFOX in First-Line Metastatic Colorectal Cancer, French Trial Concludes

NANTES, FranceTEGAFOX, a new regimen combining oxaliplatin(Drug information on oxaliplatin) (Eloxatin) with tegafur(Drug information on tegafur)-uracil (UFT) and leucovorin (LV), is feasible for outpatient use, and it offers promising survival outcomes as first-line treatment of metastatic colorectal cancer, results from two French multicenter phase II trials indicate (abstract 3545). Promising and very similar results also were seen for TEGAFIRI, another new regimen combining irinotecan (CPT-11, Camptosar) with UFT/LV, an orally available treatment. Tegafur is a fluorouracil(Drug information on fluorouracil) (5-FU) prodrug (see Figure 1); in previous randomized phase III trials, UFT/LV has been shown to have efficacy comparable to intravenous 5-FU/LV. Median survival time was 18.2 months for TEGAFOX and 15.4 months for TEGAFIRI, in the range of what has been reported for the standard- of-care FOLFOX or FOLFIRI regimens, reported investigator Jean- Yves Douillard, MD, PhD, head of the department of medical oncology at Centre Rene Gauducheau, University of Nantes, Nantes, France. "The message is that tegafur-uracil can substitute for infusional 5-FU" in the established FOLFOX or FOLFIRI regimens, he emphasized. "The response rate for both TEGAFOX and TEGAFIRI was a little lower than what we have observed in FOLFIRI and FOLFOX, but the median survival time is in the range of what is obtained now with these combinations," Dr. Douillard said at an ASCO poster session. Slightly different toxicity profiles were observed. While diarrhea was frequently observed with either regimen, FOLFOX was associated with more peripheral neuropathy, as expected, and neutropenia was more common with FOLFIRI. In all cases, toxicities were "manageable, reversible, and noncumulative," the investigators said. Two Trials
The investigators conducted two phase II trials, one evaluating UFT/LV with oxaliplatin, and the other assessing UFT/LV with irinotecan(Drug information on irinotecan), as firstline treatment of patients with measurable, nonresectable metastatic colorectal cancer. A total of 64 patients were enrolled in the TEGAFOX trial, and 56 were enrolled in the TEGAFIRI trial. The TEGAFOX regimen consisted of IV oxaliplatin (130 mg/m²) on day 1, along with UFT (300 mg/m²) and LV (90 mg) on days 1-14, repeated every 3 weeks. In the TEGAFIRI trial, IV irinotecan (250 mg/m²) was given on day 1, along with a lower dose of UFT (250 mg/m²) and LV (90 mg) on days 1-14, repeated every 3 weeks. The overall response rate for TEGAFOX was about 34%; this included 1 complete response and 19 partial responses out of 58 evaluable patients. The overall response rate was 33% for TEGAFIRI, including 1 complete and 16 partial responses out of 51 evaluable patients. Median survival time for patients in the TEGAFOX trial was 18.2 months (95% confidence interval [CI], 10-20.7) and for TEGAFIRI was 15.4 months (95% CI, 11.7-17.0) Based on these "encouraging" efficacy results, investigators said, both TEGAFOX and TEGAFIRI "offer a promising alternative to the intravenous route" that should be confirmed in phase III trials. The two regimens are "just as well tolerated," said Dr. Douillard. "I would consider that both are equivalent. Of course, we would need a randomized trial to show that." The TEGAFIRI regimen plus cetuximab(Drug information on cetuximab) (Erbitux) is now being evaluated in a trial with endpoints of response and time to progression, he added.