A Phase II Study for Short Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy (IMRT) in Combination With Capecitabine in Patients With Resectable Rectal Carcinoma
Preoperative chemoradiotherapy has become a standard part of treatment protocols in stage II
and III rectal cancer. Compared to postoperative chemoradiotherapy, the advantage of
preoperative application of chemotherapeutics and irradiation includes improved compliance,
reduced toxicity, and downstaging of the tumor in a substantial number of patients. The
latter may enhance the rate of curative surgery, permit sphincter preservation in patients
with low-sited tumors, and have a positive impact on the quality of life of these patients
(Sauer et al, 2004).
The most widely used chemotherapeutic agent in colorectal cancer has been 5-fluorouracil
(5-FU), and numerous attempts have been made to improve its efficacy, including
biomodulation and protracted infusion. It has been demonstrated that biomodulation with
leucovorin or levamisole was not effective in rectal cancer (Tepper et al, 2002), and
protracted infusion of 5-FU was superior to bolus injection (O'Connell et al, 1994). New
oral chemotherapeutic agents including capecitabine have been introduced and tried in
colorectal cancer. Capecitabine is a tumor-selective fluoropyrimidine carbamate designed to
achieve a higher intratumoral 5-FU level with lower systemic toxicity than intravenous
administration of 5-FU (Shimma et al, 2000). It passes intact through the intestinal mucosa
and is converted to 5-FU, preferentially in tumor tissue by thymidine phosphorylase
(Schuller et al, 2000 ; Ishikawa et al, 1998 ; Miwa et al, 1998). Theoretically, oral
capecitabine mimics the effect of protracted infusion of 5-FU without complications
accompanying intravenous delivery (Liu et al, 1997). Moreover, experimental data using human
cancer xenografts demonstrated up-regulation of thymidine phosphorylase by radiation (Sawada
et al, 1999), constituting a synergistic effect. In two randomized Phase III trials,
capecitabine showed a superior overall response rate and safety profile compared with
5-FU/lecovorinin for metastatic colorectal cancer (Van Cutsem et al, 2001; Hoff et al, 2001;
Twelves, 2002). Intensity modulated radiotherapy (IMRT)-based radiation therapy that
delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause
less damage to normal tissue. (Ballonoff et al, 2008)
With such encouraging outcomes, investigators initiated a prospective study to evaluate the
efficacy and toxicity of short course preoperative chemoradiotherapy utilizing Intensity
Modulated Radiation Therapy (IMRT) in combination with capecitabine in patients with
resectable rectal carcinoma.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate if downstaging of tumor is observed after preoperative chemoradiotherapy: pathological T stage of disease in surgical specimen will be compared with preoperative T stage.
Every 21 days
Yes
Weiguo Cao, MD
Principal Investigator
Ruijin Hospital
China: Food and Drug Administration
RJYY200907001
NCT00973778
July 2009
July 2012
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