Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer.
OBJECTIVE
The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated.


METHODS
There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment.


RESULTS
Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients).


CONCLUSIONS
This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer.
Seong
J
J
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Korea. jsseong@yumc.yonsei.ac.kr
Cho
J H
JH
Kim
N K
NK
Min
J S
JS
Suh
C O
CO
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000139:chemically induced / Q000209:etiology; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011878:Radiotherapy / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D013921:Thrombocytopenia / Q000139:chemically induced / Q000209:etiology
D005467:Floxuridine; D002955:Leucovorin; C025034:doxifluridine