Prospective Randomized Trial Comparing Intravenous 5 Fluorouracil and Oral Doxifluridine as Preoperative Concurrent Chemoradiation for Locally Advanced Rectal Cancer

ABSTRACT

PURPOSE: Preoperative radiation treatment with concomittant intravenous infusion of 5-fluorouracil has been known to be effective in shrinking and downstaging the tumor. Treatment with Doxifluridine (synthetic 5-deoxynucleoside derivative) medication prolongs drug exposure to tumor tissue, so it can be considered synergistic to concurrent radiotherapy. Intravenous 5-FU and oral Doxifluridine were compared with respect to tumor response, toxicity, and quality of life of patients. METHODS: Twenty eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998 were included. Intravenous 5-FU (450 mg/m2/day) and leucovorin (20 mg/m2) was given for five consecutive days during first and fifth weeks of irradiation therapy (50.4 Gy) (N=14). Oral Doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) was given daily during radiation treatment (N=14). Quality of life was scored according to twenty two activity items (good >77, fair >58, poor <57). Surgical resection was performed four weeks after completion of concurrent chemoradiation treatment. Tumor response was classified as CR (Complete Response), PR (Partial Response 50% diminution of tumor volume or downstaging), or NR (No Response). RESULTS: Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in oral arm (p=0.16, 0.23, 0.24, respectively). Quality of life was poor (36.4% vs 33.3%), fair and good (63.6% vs 66.7%, respectively) between IV arm and oral arm. Systemic recurrence during follow up periods was 1/14 (7.1%) in IV arm and 2/14 (14.3%) in oral arm, respectively (p=0.307). One local recurrence was observed in oral arm. Hematologic toxicity was 3/14 (21.4%) in IV arm versus 4/14 (28.5%) in oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) versus 5/14 (35.7%) and stomatitis was observed in IV arm (1/14, 7.1%) CONCLUSION: Oral doxifluridine based chemotherapy shows a comparable tumor response and oncologic results, but there was no benefits as far as quality of life and toxicity were concerned.