Efficacy endpoints of radiation therapy group protocol 0247

A randomized, phase 2 study of neoadjuvant radiation therapy plus concurrent capecitabine and irinotecan or capecitabine and oxaliplatin for patients with locally advanced rectal cancer

Stuart J. Wong, Jennifer Moughan, Neal J. Meropol, Pramila Rani Anne, Lisa A. Kachnic, Asif Rashid, James C. Watson, Edith P. Mitchell, Jondavid Pollock, R. Jeffrey Lee, Michael Haddock, Beth A. Erickson, Christopher G. Willett

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m2/d Monday-Friday) plus irinotecan (50 mg/m2/wk × 4); and (2) capecitabine (1650 mg/m2/d Monday-Friday) plus oxaliplatin (50 mg/m2/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2; 5-fluorouracil 2400 mg/m2) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local - regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.

Original languageEnglish (US)
Pages (from-to)116-123
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume91
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

oxaliplatin
irinotecan
Neoadjuvant Therapy
Rectal Neoplasms
radiation therapy
Radiotherapy
cancer
Fluorouracil
Disease-Free Survival
Survival
chemotherapy
Radiation Oncology
Leucovorin
Capecitabine
Cytotoxins
Adjuvant Chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Efficacy endpoints of radiation therapy group protocol 0247 : A randomized, phase 2 study of neoadjuvant radiation therapy plus concurrent capecitabine and irinotecan or capecitabine and oxaliplatin for patients with locally advanced rectal cancer. / Wong, Stuart J.; Moughan, Jennifer; Meropol, Neal J.; Anne, Pramila Rani; Kachnic, Lisa A.; Rashid, Asif; Watson, James C.; Mitchell, Edith P.; Pollock, Jondavid; Lee, R. Jeffrey; Haddock, Michael; Erickson, Beth A.; Willett, Christopher G.

In: International Journal of Radiation Oncology Biology Physics, Vol. 91, No. 1, 01.01.2015, p. 116-123.

Research output: Contribution to journalArticle

Wong, Stuart J. ; Moughan, Jennifer ; Meropol, Neal J. ; Anne, Pramila Rani ; Kachnic, Lisa A. ; Rashid, Asif ; Watson, James C. ; Mitchell, Edith P. ; Pollock, Jondavid ; Lee, R. Jeffrey ; Haddock, Michael ; Erickson, Beth A. ; Willett, Christopher G. / Efficacy endpoints of radiation therapy group protocol 0247 : A randomized, phase 2 study of neoadjuvant radiation therapy plus concurrent capecitabine and irinotecan or capecitabine and oxaliplatin for patients with locally advanced rectal cancer. In: International Journal of Radiation Oncology Biology Physics. 2015 ; Vol. 91, No. 1. pp. 116-123.
@article{d3734edbc54d4be7b32ed74616ac10a7,
title = "Efficacy endpoints of radiation therapy group protocol 0247: A randomized, phase 2 study of neoadjuvant radiation therapy plus concurrent capecitabine and irinotecan or capecitabine and oxaliplatin for patients with locally advanced rectal cancer",
abstract = "Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21{\%}) to merit further study, whereas RT with capecitabine plus irinotecan did not (10{\%}). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m2/d Monday-Friday) plus irinotecan (50 mg/m2/wk × 4); and (2) capecitabine (1650 mg/m2/d Monday-Friday) plus oxaliplatin (50 mg/m2/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2; 5-fluorouracil 2400 mg/m2) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local - regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68{\%}, 85{\%}, 16{\%}, 24{\%}, and 2{\%}, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62{\%}, 75{\%}, 18{\%}, 30{\%}, and 6{\%}, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.",
author = "Wong, {Stuart J.} and Jennifer Moughan and Meropol, {Neal J.} and Anne, {Pramila Rani} and Kachnic, {Lisa A.} and Asif Rashid and Watson, {James C.} and Mitchell, {Edith P.} and Jondavid Pollock and Lee, {R. Jeffrey} and Michael Haddock and Erickson, {Beth A.} and Willett, {Christopher G.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.ijrobp.2014.09.031",
language = "English (US)",
volume = "91",
pages = "116--123",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Efficacy endpoints of radiation therapy group protocol 0247

T2 - A randomized, phase 2 study of neoadjuvant radiation therapy plus concurrent capecitabine and irinotecan or capecitabine and oxaliplatin for patients with locally advanced rectal cancer

AU - Wong, Stuart J.

AU - Moughan, Jennifer

AU - Meropol, Neal J.

AU - Anne, Pramila Rani

AU - Kachnic, Lisa A.

AU - Rashid, Asif

AU - Watson, James C.

AU - Mitchell, Edith P.

AU - Pollock, Jondavid

AU - Lee, R. Jeffrey

AU - Haddock, Michael

AU - Erickson, Beth A.

AU - Willett, Christopher G.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m2/d Monday-Friday) plus irinotecan (50 mg/m2/wk × 4); and (2) capecitabine (1650 mg/m2/d Monday-Friday) plus oxaliplatin (50 mg/m2/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2; 5-fluorouracil 2400 mg/m2) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local - regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.

AB - Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m2/d Monday-Friday) plus irinotecan (50 mg/m2/wk × 4); and (2) capecitabine (1650 mg/m2/d Monday-Friday) plus oxaliplatin (50 mg/m2/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2; 5-fluorouracil 2400 mg/m2) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local - regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.

UR - http://www.scopus.com/inward/record.url?scp=84922975792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922975792&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2014.09.031

DO - 10.1016/j.ijrobp.2014.09.031

M3 - Article

VL - 91

SP - 116

EP - 123

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 1

ER -