Preoperative tegafur suppositories for resectable rectal cancer: phase II trial.
OBJECTIVE
Preoperative radiochemotherapy for rectal cancer causes a high rate of moderate-to-severe toxicities and is associated with only moderate survival benefits. A simpler, safer, and more convenient treatment would be preferable. Preoperative tegafur suppositories (1,500 mg/day) for at least 14 days were piloted.


METHODS
A total of 129 patients with resectable rectal cancer were enrolled. The primary end points were pathologic response, adverse events, rate of sphincter-sparing surgery, recurrence, and survival.


RESULTS
The total dose of tegafur ranged from 21 to 78 (mean, 32) g. The anal sphincter was preserved in 60.5 percent with microscopic no residual tumor (R0). The overall morbidity rate was 32 percent. Wound infection occurred in 13.2 percent of cases and anastomotic leakage in 9 percent of cases. Pathologic responses were observed in 70 percent of patients, with a complete necrosis occurring in 3.9 percent, two-thirds or more necrosis in 6.2 percent, one-third or more but less than two-thirds necrosis in 18.6 percent, and less than one-third necrosis in 41.9 percent. The mean total dose that patients showing complete or two-thirds or more necrosis received was 42.8 +/- 6.4 g (P = 0.01) compared with 31.6 +/- 1.2 g administered to patients showing less than two-thirds necrosis. Adverse events were observed in 15.6 percent of patients overall, and Grade III or IV events were observed in 2.3 percent of patients. During a median follow-up of 48 months, distant metastasis occurred in 14.7 percent of patients and local recurrence occurred in 6.2 percent of patients. The four-year, disease-free and overall survival rates were 67.6 and 80.1 percent, respectively.


CONCLUSIONS
Preoperative tegafur suppositories are associated with low toxicity and may lead to anal sphincter-sparing surgery with acceptable postoperative complications and favorable local and distal control.
Ohwada
Susumu
S
Gunma Oncology Study Group, and Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi 371-8511, Gunma, Japan. sohwada@med.gunma-u.ac.jp
Sato
Yoshihiro
Y
Izumi
Masaru
M
Kashiwabara
Kenji
K
Ogawa
Tetsushi
T
Hamada
Kunihiro
K
Kawate
Susumu
S
Nakamura
Seiji
S
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011183:Postoperative Complications / Q000453:epidemiology; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013488:Suppositories; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D013488:Suppositories; D005641:Tegafur