Phase II trial of preoperative radiation with Concurrent Capecitabine, Oxaliplatin, and Bevacizumab followed by surgery and postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: 5-year clinical outcomes Ecog-Acrin cancer research group E3204

Jerome C. Landry*, Yang Feng, Roshan S. Prabhu, Steven J. Cohen, Charles A. Staley, Richard Whittington, Elin Ruth Sigurdson, Halla S Nimeiri, Udit Verma, Al B Benson III

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leuco-vorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. Methods. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m2 b.i.d. Monday-Friday), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles).The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Results. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive.The 5-year relapse-free survival rate was 81%. Conclusion. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excel lent. However, the neoadjuvant andl surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The Oncologist.

Original languageEnglish (US)
Pages (from-to)615-616
Number of pages2
JournalOncologist
Volume20
Issue number6
DOIs
StatePublished - Jan 1 2015

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oxaliplatin
Leucovorin
Rectal Neoplasms
Fluorouracil
Radiation
Research
Neoplasms
Radiotherapy
Survival Rate
Recurrence
Capecitabine
Bevacizumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{016493e76e6b48a4b7e0407e7687054b,
title = "Phase II trial of preoperative radiation with Concurrent Capecitabine, Oxaliplatin, and Bevacizumab followed by surgery and postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: 5-year clinical outcomes Ecog-Acrin cancer research group E3204",
abstract = "Background. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leuco-vorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. Methods. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m2 b.i.d. Monday-Friday), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles).The primary endpoint was a pathologic complete response (path-CR) rate of 30{\%}. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Results. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91{\%}) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17{\%}) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54{\%}) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80{\%}. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive.The 5-year relapse-free survival rate was 81{\%}. Conclusion. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excel lent. However, the neoadjuvant andl surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The Oncologist.",
author = "Landry, {Jerome C.} and Yang Feng and Prabhu, {Roshan S.} and Cohen, {Steven J.} and Staley, {Charles A.} and Richard Whittington and Sigurdson, {Elin Ruth} and Nimeiri, {Halla S} and Udit Verma and {Benson III}, {Al B}",
year = "2015",
month = "1",
day = "1",
doi = "10.1634/theoncologist.2015-0106",
language = "English (US)",
volume = "20",
pages = "615--616",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",
number = "6",

}

Phase II trial of preoperative radiation with Concurrent Capecitabine, Oxaliplatin, and Bevacizumab followed by surgery and postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer : 5-year clinical outcomes Ecog-Acrin cancer research group E3204. / Landry, Jerome C.; Feng, Yang; Prabhu, Roshan S.; Cohen, Steven J.; Staley, Charles A.; Whittington, Richard; Sigurdson, Elin Ruth; Nimeiri, Halla S; Verma, Udit; Benson III, Al B.

In: Oncologist, Vol. 20, No. 6, 01.01.2015, p. 615-616.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II trial of preoperative radiation with Concurrent Capecitabine, Oxaliplatin, and Bevacizumab followed by surgery and postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer

T2 - 5-year clinical outcomes Ecog-Acrin cancer research group E3204

AU - Landry, Jerome C.

AU - Feng, Yang

AU - Prabhu, Roshan S.

AU - Cohen, Steven J.

AU - Staley, Charles A.

AU - Whittington, Richard

AU - Sigurdson, Elin Ruth

AU - Nimeiri, Halla S

AU - Verma, Udit

AU - Benson III, Al B

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leuco-vorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. Methods. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m2 b.i.d. Monday-Friday), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles).The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Results. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive.The 5-year relapse-free survival rate was 81%. Conclusion. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excel lent. However, the neoadjuvant andl surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The Oncologist.

AB - Background. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leuco-vorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. Methods. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m2 b.i.d. Monday-Friday), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles).The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Results. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive.The 5-year relapse-free survival rate was 81%. Conclusion. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excel lent. However, the neoadjuvant andl surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The Oncologist.

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