Preoperative chemoradiation with irinotecan and capecitabine in patients with locally advanced resectable rectal cancer: long-term results of a Phase II study.
OBJECTIVE
Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen.


METHODS
Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40 mg/m(2) of irinotecan per week for 5 consecutive weeks and 1,650 mg/m(2) of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints.


RESULTS
In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death.


CONCLUSIONS
Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.
Hong
Yong Sang
YS
Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.
Kim
Dae Yong
DY
Lim
Seok-Byung
SB
Choi
Hyo Seong
HS
Jeong
Seung-Yong
SY
Jeong
Jun Yong
JY
Sohn
Dae Kyung
DK
Kim
Dae-Hyun
DH
Chang
Hee Jin
HJ
Park
Jae-Gahb
JG
Jung
Kyung Hae
KH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012074:Remission Induction; D015996:Survival Rate
D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin