TY - JOUR
T1 - Preoperative chemoradiation for locally advanced rectal cancer
T2 - emerging treatment strategies.
AU - Crane, Christopher H.
AU - Janjan, Nora A.
AU - Mason, Kathy
AU - Milas, Luka
PY - 2002/5
Y1 - 2002/5
N2 - Over the past decade, patients with locally advanced rectal cancer at The University of Texas M. D. Anderson Cancer Center have been managed with preoperative chemoradiation. Patients achieving a complete clinical response to preoperative chemoradiation have had better pelvic tumor control, sphincterpreservation, and overall survival than those with gross residual disease. Some patients achieving a complete clinical response have even had rectal-preserving surgery (full-thickness local excision). These results emphasize the importance of maximizing tumor response. Further improvement in response and survival could be achieved by using novel chemotherapeutic agents or through tumor-selective molecular targeting strategies that enhance the effects of chemotherapy, radiotherapy, or both. Irinotecan (CPT-11, Camptosar) is a novel chemotherapy agent being evaluated clinically as a radiosensitizing agent in rectal cancer. Inhibition of several molecular targets-such as epidermal growth factor receptor, ras oncogene activation, the cyclooxygenase-2 (COX-2) enzyme, and neoangiogenesis-appears to be tumor-selective in preclinical models. COX-2 expression has been shown to enhance cytotoxic therapy in preclinical models. In vitro and in vivo studies show that selective COX-2 inhibition enhances the effects of radiotherapy as well as chemotherapy. COX-2 is also markedly upregulated in human colorectal cancer and appears to be associated with adverse patient prognosis. Thus, integration of molecular targeting, such as COX-2 selective inhibition with existing chemoradiation approaches, may provide selective tumor radiosensitization and chemosensitization, resulting in improved pelvic control, sphincter preservation, and overall survival.
AB - Over the past decade, patients with locally advanced rectal cancer at The University of Texas M. D. Anderson Cancer Center have been managed with preoperative chemoradiation. Patients achieving a complete clinical response to preoperative chemoradiation have had better pelvic tumor control, sphincterpreservation, and overall survival than those with gross residual disease. Some patients achieving a complete clinical response have even had rectal-preserving surgery (full-thickness local excision). These results emphasize the importance of maximizing tumor response. Further improvement in response and survival could be achieved by using novel chemotherapeutic agents or through tumor-selective molecular targeting strategies that enhance the effects of chemotherapy, radiotherapy, or both. Irinotecan (CPT-11, Camptosar) is a novel chemotherapy agent being evaluated clinically as a radiosensitizing agent in rectal cancer. Inhibition of several molecular targets-such as epidermal growth factor receptor, ras oncogene activation, the cyclooxygenase-2 (COX-2) enzyme, and neoangiogenesis-appears to be tumor-selective in preclinical models. COX-2 expression has been shown to enhance cytotoxic therapy in preclinical models. In vitro and in vivo studies show that selective COX-2 inhibition enhances the effects of radiotherapy as well as chemotherapy. COX-2 is also markedly upregulated in human colorectal cancer and appears to be associated with adverse patient prognosis. Thus, integration of molecular targeting, such as COX-2 selective inhibition with existing chemoradiation approaches, may provide selective tumor radiosensitization and chemosensitization, resulting in improved pelvic control, sphincter preservation, and overall survival.
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M3 - Review article
C2 - 12109806
AN - SCOPUS:0036561182
SN - 0890-9091
VL - 16
SP - 39
EP - 44
JO - Oncology (Williston Park, N.Y.)
JF - Oncology (Williston Park, N.Y.)
IS - 5 Suppl 5
ER -