Randomized Phase II Trial of Preoperative Chemoradiation With or Without Induction Chemotherapy In Patients With Locally Advanced Or Borderlinely Resectable Rectal Cancer With Resectable Synchronous Liver Metastases
Preoperative chemoradiation is now an initial treatment of choice for locally advanced
resectable rectal cancer, and 5-fluorouracil is the standard agent during chemoradiation.
Capecitabine is an oral fluoropyrimidine which has been thought to be a replacement for
intravenous 5-fluorouracil, and several trials have proved that preoperative chemoradiation
with capecitabine was also effective in this setting.
Oxaliplatin, a newer platinum agent, plus fluoropyrimidines (either 5-fluorouracil or
capecitabine) is one of the standard cytotoxic chemotherapeutic regimen for metastatic
colorectal cancer, and it is also proved to be effective as neoadjuvant chemotherapy for
patients with liver only metastasis from colorectal cancer.
Approximately 25% of patients with colorectal cancer have liver metastases initially at the
time of diagnosis and there have been quite well established evidences for clear survival
benefits from hepatic metastasectomy in these patients. Treatment for colorectal liver
metastases should be planned with consideration of both systemic chemotherapy and local
treatment modality (surgery or radiofrequency ablation) because long term survival would be
expected after curative liver metastasectomy. As mentioned previously, neoadjuvant
oxaliplatin plus fluoropyrimidines before hepatic metastasectomy improved disease-free
survival, thus it is thought to be that better systemic controls would be achieved with
perioperative oxaliplatin based chemotherapy.
In patients with locally advanced rectal cancer, preoperative chemoradiation with
fluoropyrimidines improves local control but not systemic control. Recent randomized trials
of preoperative chemoradiation with oxaliplatin plus fluoropyrimidines failed to show better
local control rates than those with fluoropyrimidines alone. But it is too early to
determine the non-superiority of preoperative chemoradiation with oxaliplatin plus
fluoropyrimidines in terms of systemic control; long-term duration of follow-up is needed to
determine the efficacy in terms of disease-free or overall survival and it is evident that
oxaliplatin based chemotherapy is effective for systemic control in patients who will be
candidate for liver metastasectomy.
Thus, the investigators planned a randomized phase II trial of preoperative chemoradiation
with oxaliplatin plus capecitabine, with or without prior induction chemotherapy in patients
with locally advanced or borderlinely resectable rectal cancer with resectable synchronous
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
R0 resection rate after simultaneous surgery of the rectum and the liver
Korea: Food and Drug Administration