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The Effect of Concurrent Chemoradiation on Circulating Endothelial Progenitor Cells in Colorectal Cancer

30 Years
60 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

The Effect of Concurrent Chemoradiation on Circulating Endothelial Progenitor Cells in Colorectal Cancer

Colorectal cancer (CRC) is one of the common malignancies worldwide, accounting for a
significant percentage of cancer mortality. The incidence in both developing and developed
countries has been increasing over the past few decades (1). Radiation therapy, either as
post-operative adjuvant treatment for resectable disease or definitive treatment along with
chemotherapy for unresectable disease, has an important role in management of this cancer

Concurrent chemoradiation (CCRT) is now a standard treatment for cervical cancer (bulky and
locally advanced lesions) (5) and unresectable malignancies of gastrointestinal system
origin (esophagus, stomach, pancreas and anorectum) (6−9). To improve quality of life, CCRT
is also commonly applied in treatment of lower rectal and anal canal cancer to preserve anal
sphincter function (9). The most commonly used chemotherapeutic drugs combined with
radiation as radiosensitizers are cis-platinum, 5-fluorouracil (5-FU) and mitomycin C (6−9).
These drugs are myelosuppressive and prone to cause life-threatening neutropenia, anemia or
thrombocytopenia, which are more severe than those with radiotherapy alone (5−9). To avoid
unnecessary over-treatment in CRC, the optimization of CCRT is of critical importance.
Herein, the development of a surrogate marker for monitoring treatment efficacy is pivotal
to optimize CCRT.

Angiogenesis is a heavily regulated process, which is involved by complex interactions
between inhibitory and stimulatory angiogenic factors. It is essential for tumor growth,
progression and metastasis and is correlated with poor prognosis in cancer patients
including CRC. Many novel compounds that potently inhibit formation of neoplastic blood
vessels have been recently developed. There is increasing interest in developing
angiogeneis-suppressive agents for colorectal cancer treatment and growing number of
anti-angiogenesis drugs currently being evaluated in clinical trials for CRC. Promising
results have been reported include an increase in overall survival and reduction in the risk
of death (Bevacizumab), reversal of cellular resistance (Cetuximab) and activity as
second-line therapy in patients who have exhausted other available treatment options
(Cetuximab, ABX-EGF, PTK-787, Gefitinib, Erlotinib) (10,11).

Although the therapeutic role of angiogenesis target therapy has been approved in cancer
treatment including CRC, the way to optimize the dose of angiogenesis inhibitors remains to
be determined because of the lack of reliable surrogate markers of tumor angiogenesis.
Shaked et al. reported that the levels of circulating endothelial progenitor cells (EPC),
which contribute to the tumor vessel formation, reflect the anti-tumor efficacy of
anti-angiogenesis regimens (12). Growing evidence suggests that the levels of circulating
EPC reflect the response to chemotherapy both in animal model and clinical trial (13,14).
Thus, circulating EPC can be used as a marker for optimizing and monitoring the
anti-angiogenesis therapy including angiogenesis inhibitors and chemotherapy.

Whether circulating EPC can be served as a marker of CCRT efficacy or not remains
undetermined. Since CCRT is now a standard treatment of locally advanced and high-risk CRC,
the development of a surrogate marker for monitoring CCRT response and optimize treatment
intensity, again, is very important.

In this grant we intent to monitor the levels of circulating EPC in locally advanced and
high-risk CRC patients before, during and after CCRT. To further characterize the changes in
function and biology of EPC caused by CCRT, a syngeneic animal model will be also used to
evaluate the clonogenecity and specific gene expression of EPC in tumor-bearing mice
receiving CCRT.


1. Midgley R, Kerr D. Colorectal cancer. Lancet 1999;353:391–399.

2. Fisher B, Wolmark N, Rockette H, et al. Postoperative adjuvant chemotherapy or
radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer
Inst 1988;80:21–29.

3. O'Connell MJ, Martenson JA, Wieand HS, et al. Improving adjuvant therapy for rectal
cancer by combining protracted-infusion fluorouracil with radiation therapy after
curative surgery. New Engl J Med 1994;331:502–507.

4. Skarlatos J, Kosma L, Koukourakis M, et al. Hypofractionated radiotherapy with
concurrent 5-fluorouracil radiosensitisation for recurrent or locally advanced
colorectal cancer. A phase II study. Int J Colore Dis 1996;11:206–210.

5. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and
chemotherapy for locally advanced cervical cancer. New Engl J Med 1999;340:1144–1153.

6. Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally advanced esophageal
cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation
Therapy Oncology Group. J Am Med Assoc 1999;281:1623–1627.

7. Henning GT, Schild SE, Stafford SL, et al. Results of irradiation or chemoirradiation
for primary unresectable, locally recurrent, or grossly incomplete resection of gastric
adenocarcinoma. Int J Radiat Oncol 2000;46:109–118.

8. Mitchell SE, Mendenhall WM, Zlotecki RA, et al. Squamous cell carcinoma of the anal
canal. Int J Radiat Oncol 2001;49:1007–1013.

9. Thomas CR, Weiden PL, Traverso LW, et al. Concomitant intraarterial cisplatin,
intravenous 5-flourouracil, and split-course radiation therapy for locally advanced
unresectable pancreatic adenocarcinoma: a phase II study of the Puget Sound Oncology
Consortium (PSOC-703). Am J Clin Oncol 1997;20:161–165.

10. Kelly H. Goldberg RM. Systemic therapy for metastatic colorectal cancer: current
options, current evidence. Journal of Clinical Oncology. 23(20):4553-60, 2005

11. Mancuso A. Sternberg CN. Colorectal cancer and antiangiogenic therapy: what can be
expected in clinical practice?. Critical Reviews in Oncology-Hematology. 55(1):67-81,
2005 Jul.

12. Schneider M. Tjwa M. Carmeliet P. A surrogate marker to monitor angiogenesis at last.
Cancer Cell. 7(1):3-4, 2005.

13. Bertolini F. Paul S. Mancuso P. Monestiroli S. Gobbi A. Shaked Y. Kerbel RS. Maximum
tolerable dose and low-dose metronomic chemotherapy have opposite effects on the
mobilization and viability of circulating endothelial progenitor cells. Cancer
Research. 63(15):4342-6, 2003.

14. Zhang H. Vakil V. Braunstein M. Smith EL. Maroney J. Chen L. Dai K. Berenson JR.
Hussain MM. Klueppelberg U. Norin AJ. Akman HO. Ozcelik T. Batuman OA. Circulating
endothelial progenitor cells in multiple myeloma: implications and significance. Blood.
105(8):3286-94, 2005

Inclusion Criteria:

- Colorectal cancer patients indicated for chemoradiation

Exclusion Criteria:

- With major systemic disease including other cancer, diabetes, cardiovacular disease.

- Received prior chemotherapy or radiotherapy within 1 month

- Receiving immunosuppressants

Type of Study:


Study Design:

Observational Model: Case Control, Time Perspective: Longitudinal, Time Perspective: Prospective

Principal Investigator

Yu-Jen Chen, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of Radiation Oncology, Mackay Memorial Hospital


Taiwan: Department of Health

Study ID:




Start Date:

April 2006

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • Colorectal Neoplasms