NOTTINGHAM, UK—In a phase III multinational study, UFT capsules (uracil/tegafur) in combination with leucovorin calcium tablets proved as effective as IV fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin, and much less toxic, when used as first-line treatment of metastatic colorec-tal cancer, James Carmichael, MD, of Nottingham City Hospital, UK, reported at the 35th annual meeting of the American Society of Clinical Oncology in Atlanta. [The FDA’s Oncologic Drugs Advisory Committee has recommended that UFT capsules plus oral leucovorin be approved for advanced colorectal cancer; a complete report will appear next month.]
The study results are consistent with data from a similar multinational trial of UFT/leucovorin, reported by Richard Pazdur, MD, at the ASCO meeting .
Dr. Carmichael reported on 380 patients randomized to receive UFT (300 mg/m²/d) plus leucovorin (90 mg/d), both administered orally for 28 days every 35 days, or 5-FU (425 mg/m²/d) plus leucovorin (20 mg/m²/d), both given intravenously for 5 days every 35 days.
Efficacy was comparable between the two arms, he said. The median time to progression was 3.4 and 3.3 months, respectively, in the oral and IV regimens (P = .591); median survival times were 12.2 and 11.9 months (P = .682); and overall response rates were 11% and 9% (P = .593). However, UFT was associated with significant reductions in the incidence and severity of major side effects, compared with 5-FU/leucovorin. The incidence of grade 3-4 stomatitis/mucositis was 2% for the oral therapy vs 16% with 5-FU/leucovorin (P < .001), and the incidence of grade 3-4 neutropenia was 3% vs 31% (P < .001). The lower incidence of severe neutropenia with the oral therapy translated into significantly fewer episodes of febrile neutropenia (P < .001) and documented infection (P = .040).
Although the incidences of diarrhea and nausea and vomiting were similar between the two groups, use of concomitant medication, including antiemetics, was significantly higher in the 5-FU/leucovorin arm, Dr. Carmichael said.
“These results show that first-line oral outpatient treatment of metastatic colorectal cancer is viable and, in fact, represents a better tolerated, more convenient option for patients,” he concluded.
