719 Doxifluridine in advanced colorectal carcinoma. Parallel multicentre randomized phase II trial

Doxifluridine (5-dFUR) is a fluoropyrimidine derivative with a better therapeutic index than FU (Bajetta, Eur J Cancer, 1993). This study independently evaluated the activity of two different schedules of oral or i.v. 5-dFUR plus levo-Ieucovorin. Between April 1993 and September 1994, a total of 130 untreated (in an adjuvant and metastatic setting) pts with measurable colorectal cancer were randomized to 5-dFUR 750 mg/m2 p.o. on days 1→4 and levo-leucovorin 25 mg/dose p.o. two hours before 5-dFUR, repeated every 12 days (Arm A); or 5-dFUR 3000 mg/m2 as a one hour i.v. infusion for 5 consecutive days combined with levo-leucovorin 25 mg/dose i.v. immediately before 5-dFUR every 21 days (Arm B). The first response evaluation was made after 2 mos of treatment. The two arms were well balanced in terms ofage (median 61 yrs, range 31–80), sex (M/F: 69/61) and disease extension. A preliminary intent-to-treat analysis was made of 126 adequately treated pts (4 too early to evaluate), of whom 67 were in Arm A and 59 in Arm B. The response rates were 15% in Arm A (2 CR, 8 PR, 29 SD, 28 PD) and 39% in Arm B (5 CR, 15 PR, 15 SD, 21 PD). Toxicity included WHO grade 3 and 4 diarrhea in respectively 16% and 7% of Arm A and 16% and 15% of Arm B respectively. Mucositis was mainly observed in Arm B (grade 3 in 13% and grade 4 in 1%). The preliminary data confirm the good tolerability profile of both the oral and the i.v. schedule. The oral route seems to be promising and is interesting, because it could be benefit for pts suitable for home treatment. Moreover, this study confirms the efficacy of i.v. doxifluridine as a fast line therapy in advanced colorectal cancer. Data management by I.T.M.O. (ltalian Trials in Medical Oncology) Scietific Service.