Preoperative Capecitabine with Pelvic Radiotherapy for Locally Advanced Rectal Cancer (Phase I Trial)
Vutisiri Veerasarn MD*, Pramook Phromratanapongse MD**, Vicharn Lorvidhaya MD***, Prasert Lertsanguansinchai MD****, Chawalit Lertbutsayanukul MD****, Apichart Panichevaluk MD*****, Wiroon Boonnuch MD******, Vitoon Chinswangwatanakul MD******, Darin Lohsiriwat MD******, Arun Rojanasakul MD*******, Parinya Thavichaigarn MD********, Paiboon Jivapaisarnpong MD*********
Affiliation : * Division of Radiation Oncology, Department of Radiology, Siriraj Hospital, Mahidol University ** Division of Radiation Oncology, Phramongkutklao Hospital *** Division of Therapeutic Radiation and Oncology, Department of Radiology, Chiang Mai University **** Division of Radiation Oncology, Department of Radiology, Chulalongkorn University ***** Division of Radiotherapy, Rajavithi Hospital ****** Department of Surgery, Siriraj Hospital, Mahidol University ******* Colorectal Division, Department of Surgery, Chulalongkorn University ******** Department of Surgery, Phramongkutklao Hospital ********* Department of Surgery, Rajavithi Hospital
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 ad-
vanced rectal cancer (LARC).
Materials and 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%).
Conclusion : 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.
Keywords : Rectal cancer, Chemoradiation, Capecitabine, Radiotherapy
