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 for mRNA 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.
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 for mRNA 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.
Authors: Bryan H Burmeister; B Mark Smithers; Val Gebski; Lara Fitzgerald; R John Simes; Peter Devitt; Stephen Ackland; David C Gotley; David Joseph; Jeremy Millar; John North; Euan T Walpole; James W Denham Journal: Lancet Oncol Date: 2005-09 Impact factor: 41.316
Authors: Robert A Meguid; Craig M Hooker; Joshua T Taylor; Laurence R Kleinberg; Stephen M Cattaneo; Marc S Sussman; Stephen C Yang; Richard F Heitmiller; Arlene A Forastiere; Malcolm V Brock Journal: J Thorac Cardiovasc Surg Date: 2009-12 Impact factor: 5.209
Authors: Michael Stahl; Martin K Walz; Martin Stuschke; Nils Lehmann; Hans-Joachim Meyer; Jorge Riera-Knorrenschild; Peter Langer; Rita Engenhart-Cabillic; Michael Bitzer; Alfred Königsrainer; Wilfried Budach; Hansjochen Wilke Journal: J Clin Oncol Date: 2009-01-12 Impact factor: 44.544
Authors: Joel Tepper; Mark J Krasna; Donna Niedzwiecki; Donna Hollis; Carolyn E Reed; Richard Goldberg; Krystyna Kiel; Christopher Willett; David Sugarbaker; Robert Mayer Journal: J Clin Oncol Date: 2008-03-01 Impact factor: 44.544
Authors: Manuel Cobo; Dolores Isla; Bartomeu Massuti; Ana Montes; Jose Miguel Sanchez; Mariano Provencio; Nuria Viñolas; Luis Paz-Ares; Guillermo Lopez-Vivanco; Miguel Angel Muñoz; Enriqueta Felip; Vicente Alberola; Carlos Camps; Manuel Domine; Jose Javier Sanchez; Maria Sanchez-Ronco; Kathleen Danenberg; Miquel Taron; David Gandara; Rafael Rosell Journal: J Clin Oncol Date: 2007-07-01 Impact factor: 44.544
Authors: Geoffrey Y Ku; Anuja Kriplani; Yelena Y Janjigian; David P Kelsen; Valerie W Rusch; Manjit Bains; Joanne Chou; Marinela Capanu; Abraham J Wu; Karyn A Goodman; David H Ilson Journal: Cancer Date: 2016-05-06 Impact factor: 6.860
Authors: Syma Iqbal; Shannon McDonough; Heinz-Josef Lenz; David Ilson; Barbara Burtness; Chaitali S Nangia; Afsaneh Barzi; Charles J Schneider; Jane Jijun Liu; Efrat Dotan; Katherine A Guthrie; Howard S Hochster Journal: J Clin Oncol Date: 2019-12-09 Impact factor: 44.544
Authors: Lawrence R Kleinberg; Paul J Catalano; Arlene A Forastiere; Steven M Keller; Edith P Mitchel; Pramila Rani Anne; Al B Benson Journal: Int J Radiat Oncol Biol Phys Date: 2015-12-18 Impact factor: 7.038