Preoperative capecitabine with pelvic radiotherapy for locally advanced rectal cancer (phase I trial).
OBJECTIVE
Phase I multicenter study defined the maximal tolerated dose (MTD), dose-limiting toxicity (DLT) and safety profile of capecitabine in combination with preoperative radiation for patients with locally advanced rectal cancer (LARC).


METHODS
Patients were treated with oral capecitabine (700, 800, 900, 1000, 1100 and 1200 mg/m2 twice daily continuously) plus preoperative whole pelvic irradiation (45-46 Gy in 23-25 fractions over 5-6 weeks). Surgery was performed at the median of 42 days after chemoradiation treatment.


RESULTS
Twenty-seven patients were in this trial. Eighteen patients (3 per dose level) had received capecitabine from 700 mg/m2 twice daily to the highest dose level of 1200 mg/m2 twice daily. There were no grade 3/4 DLTs during dose escalation, a further nine patients were included at the highest capecitabine dose. Two of the twelve patients (16%) receiving capecitabine 1200 mg/m2 twice daily developed grade 3 diarrhea and discontinued treatment. There were no other grade 3/4 adverse events. After capecitabine chemoradiation, 24 of 27 patients (89%) received definite surgery. Primary and lymph node down staging occurred in ten patients (42%). Sphincter-sparing surgery was performed in seven patients (26%) and abdominal-perineal resection was performed in 17 patients (63%).


CONCLUSIONS
Preoperative capecitabine chemoradiation based on continuous daily capecitabine is very well tolerated in patients with LARC. The authors did not reach the MTD in the present study.
Veerasarn
Vutisiri
V
Radiation Oncology, Department of Radiology, Siriraj Hospital, Faculty of Medicine, Mahidol University, 2 Prannok Rd, Bangkoknoi, Bangkok 10700, Thailand. vutisiri@hotmail.com
Phromratanapongse
Pramook
P
Lorvidhaya
Vicharn
V
Lertsanguansinchai
Prasert
P
Lertbutsayanukul
Chawalit
C
Panichevaluk
Apichart
A
Boonnuch
Wiroon
W
Chinswangwatanakul
Vitoon
V
Lohsiriwat
Darin
D
Rojanasakul
Arun
A
Thavichaigarn
Parinya
P
Jivapaisarnpong
Paiboon
P
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil