BACKGROUND: in the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancer patients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity. MATERIAL AND METHODS: this review article focuses on phase II-III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancer patients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. RESULTS: after preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal, or investigator's discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease. CONCLUSION: whether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial.
BACKGROUND: in the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancerpatients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity. MATERIAL AND METHODS: this review article focuses on phase II-III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancerpatients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. RESULTS: after preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal, or investigator's discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease. CONCLUSION: whether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial.
Authors: B Michael Ghadimi; Marian Grade; Michael J Difilippantonio; Sudhir Varma; Richard Simon; Cristina Montagna; Laszlo Füzesi; Claus Langer; Heinz Becker; Torsten Liersch; Thomas Ried Journal: J Clin Oncol Date: 2005-03-20 Impact factor: 44.544
Authors: Mark S Roh; Linda H Colangelo; Michael J O'Connell; Greg Yothers; Melvin Deutsch; Carmen J Allegra; Morton S Kahlenberg; Luis Baez-Diaz; Carol S Ursiny; Nicholas J Petrelli; Norman Wolmark Journal: J Clin Oncol Date: 2009-09-21 Impact factor: 44.544
Authors: Roy F A Vliegen; Regina G Beets-Tan; Bart Vanhauten; Ann Driessen; Michel Oellers; Alfons G Kessels; Ann Arens; Geerard L Beets; Jeroen Buijsen; Angela van Baardwijk; Dirk de Ruysscher; Guido Lammering Journal: Strahlenther Onkol Date: 2008-09-19 Impact factor: 3.621
Authors: Claudio V Sole; Felipe A Calvo; Carlos Ferrer; Emilio Alvarez; Jose L Carreras; Enrique Ochoa Journal: Eur J Nucl Med Mol Imaging Date: 2014-10-01 Impact factor: 9.236
Authors: Shu Y Ng; Kathryn L Colborn; Lajhem Cambridge; Andrea Cercek; Diane L Reidy-Lagunes; Neil Segal; Zsofia Stadler; Leonard B Saltz; Philip B Paty; Jose Guillem; Martin R Weiser; Garrett Nash; Julio Garcia-Aguilar; Karyn A Goodman Journal: Clin Colorectal Cancer Date: 2019-04-06 Impact factor: 4.481