S0356: A phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma

Lawrence P. Leichman, Bryan H. Goldman, Pierre O. Bohanes, Heinz J. Lenz, Charles Thomas, Kevin Billingsley, Christopher Corless, Syma Iqbal, Philip J. Gold, Jacqueline K. Benedetti, Kathleen D. Danenberg, Charles Blanke

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose: Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40% with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival. Patients and Methods: Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m 2 on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m 2/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.8 Gy/d for 25 fractions; surgery was performed 28 to 42 days after neoadjuvant therapy. Chemotherapy was planned after surgery. Tumors were analyzed form RNA expression and polymorphisms in genes involved in drug metabolism and DNA repair. Results: Ninety-three patients were evaluable. Two deaths (2.2%) were attributable to preoperative therapy, and two deaths (2.2%) were attributable to surgery. Grade 3 and 4 toxicities were recorded for 47.3% and 19.4% of patients, respectively. Seventy-nine patients (84.9%) underwent surgery; 67.7% of patients had R0 resections. Twenty-six patients (28.0%) had confirmed pCR (95% CI, 19.1% to 38.2%). At a median follow-up of 39.2 months, estimates of median and 3-year overall survival (OS) were 28.3 months and 45.1%, respectively. Intratumoral ERCC-1 gene expression was inversely related to progression-free survival and OS. Conclusion: Neoadjuvant oxaliplatin, PI-FU, and EBRT for esophageal adenocarcinoma is active and tolerable. Because the regimen failed to meet the primary end point, it does not define a new standard. However, future trials can be built on this platform to validate the role of ERCC-1 in determining the best systemic regimen for individual patients.

Original languageEnglish (US)
Pages (from-to)4555-4560
Number of pages6
JournalJournal of Clinical Oncology
Volume29
Issue number34
DOIs
StatePublished - Dec 1 2011

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oxaliplatin
Fluorouracil
Adenocarcinoma
Radiotherapy
Neoadjuvant Therapy
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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S0356 : A phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma. / Leichman, Lawrence P.; Goldman, Bryan H.; Bohanes, Pierre O.; Lenz, Heinz J.; Thomas, Charles; Billingsley, Kevin; Corless, Christopher; Iqbal, Syma; Gold, Philip J.; Benedetti, Jacqueline K.; Danenberg, Kathleen D.; Blanke, Charles.

In: Journal of Clinical Oncology, Vol. 29, No. 34, 01.12.2011, p. 4555-4560.

Research output: Contribution to journalArticle

Leichman, Lawrence P. ; Goldman, Bryan H. ; Bohanes, Pierre O. ; Lenz, Heinz J. ; Thomas, Charles ; Billingsley, Kevin ; Corless, Christopher ; Iqbal, Syma ; Gold, Philip J. ; Benedetti, Jacqueline K. ; Danenberg, Kathleen D. ; Blanke, Charles. / S0356 : A phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 34. pp. 4555-4560.
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abstract = "Purpose: Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40{\%} with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival. Patients and Methods: Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m 2 on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m 2/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.8 Gy/d for 25 fractions; surgery was performed 28 to 42 days after neoadjuvant therapy. Chemotherapy was planned after surgery. Tumors were analyzed form RNA expression and polymorphisms in genes involved in drug metabolism and DNA repair. Results: Ninety-three patients were evaluable. Two deaths (2.2{\%}) were attributable to preoperative therapy, and two deaths (2.2{\%}) were attributable to surgery. Grade 3 and 4 toxicities were recorded for 47.3{\%} and 19.4{\%} of patients, respectively. Seventy-nine patients (84.9{\%}) underwent surgery; 67.7{\%} of patients had R0 resections. Twenty-six patients (28.0{\%}) had confirmed pCR (95{\%} CI, 19.1{\%} to 38.2{\%}). At a median follow-up of 39.2 months, estimates of median and 3-year overall survival (OS) were 28.3 months and 45.1{\%}, respectively. Intratumoral ERCC-1 gene expression was inversely related to progression-free survival and OS. Conclusion: Neoadjuvant oxaliplatin, PI-FU, and EBRT for esophageal adenocarcinoma is active and tolerable. Because the regimen failed to meet the primary end point, it does not define a new standard. However, future trials can be built on this platform to validate the role of ERCC-1 in determining the best systemic regimen for individual patients.",
author = "Leichman, {Lawrence P.} and Goldman, {Bryan H.} and Bohanes, {Pierre O.} and Lenz, {Heinz J.} and Charles Thomas and Kevin Billingsley and Christopher Corless and Syma Iqbal and Gold, {Philip J.} and Benedetti, {Jacqueline K.} and Danenberg, {Kathleen D.} and Charles Blanke",
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AU - Bohanes, Pierre O.

AU - Lenz, Heinz J.

AU - Thomas, Charles

AU - Billingsley, Kevin

AU - Corless, Christopher

AU - Iqbal, Syma

AU - Gold, Philip J.

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AU - Danenberg, Kathleen D.

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N2 - Purpose: Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40% with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival. Patients and Methods: Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m 2 on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m 2/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.8 Gy/d for 25 fractions; surgery was performed 28 to 42 days after neoadjuvant therapy. Chemotherapy was planned after surgery. Tumors were analyzed form RNA expression and polymorphisms in genes involved in drug metabolism and DNA repair. Results: Ninety-three patients were evaluable. Two deaths (2.2%) were attributable to preoperative therapy, and two deaths (2.2%) were attributable to surgery. Grade 3 and 4 toxicities were recorded for 47.3% and 19.4% of patients, respectively. Seventy-nine patients (84.9%) underwent surgery; 67.7% of patients had R0 resections. Twenty-six patients (28.0%) had confirmed pCR (95% CI, 19.1% to 38.2%). At a median follow-up of 39.2 months, estimates of median and 3-year overall survival (OS) were 28.3 months and 45.1%, respectively. Intratumoral ERCC-1 gene expression was inversely related to progression-free survival and OS. Conclusion: Neoadjuvant oxaliplatin, PI-FU, and EBRT for esophageal adenocarcinoma is active and tolerable. Because the regimen failed to meet the primary end point, it does not define a new standard. However, future trials can be built on this platform to validate the role of ERCC-1 in determining the best systemic regimen for individual patients.

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