PURPOSE: Preoperative chemoradiotherapy is a primary treatment option for patients with resectable esophageal cancer. Combination regimens using newer agents may improve patient outcomes. This multicenter community-based phase I/II trial examined a modern triplet regimen comprised of oxaliplatin, docetaxel, and capecitabine (ODC) combined with radiation therapy (RT). PATIENTS AND METHODS: The primary end point was the pathologic complete response (pCR) rate. Eligibility criteria included resectable stage I to III cancer of the mid-/distal-esophagus or gastroesophageal junction, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Treatment included oxaliplatin 40 mg/m(2), docetaxel 20 mg/m(2) (intravenous, weekly x 5); capecitabine 1,000 mg/m(2) orally twice daily on days 1 to 7, 15 to 21, and 29 to 35; and concurrent RT (45 Gy). Resection was performed during weeks 9 to 12. ODC and RT safety was determined in a phase I portion (n = 10) preceding phase II. RESULTS: Fifty-nine patients were enrolled (September 2005 to February 2008; phase I/cohort 1, 10 patients; phase I/cohort 2/phase II, 49 patients). Baseline characteristics included median age of 63 years; 84% male; ECOG PS 0 and 1, 51% and 49%, respectively; adenocarcinoma and squamous cell, 69% and 18%, respectively; stage I, II, and III, 12%, 41%, and 45%, respectively. Phase I revealed no dose-limiting toxicity. Responses: pCR rate, 49%; objective response rate, 61% (24 complete and six partial responses); stable disease, 6%; and progressive disease, 2%. Sixty-nine percent of patients underwent surgery. Survival: median follow-up, 116 weeks; median disease-free survival (DFS) and overall survival (OS) were 16.3 and 24.1 months, respectively. Two-year DFS and OS were 45.1% and 52.2%, respectively. Most common (>or= 5%) grade 3 to 4 nonhematologic toxicities were anorexia (20%), dehydration (16%), diarrhea (8%), dysphagia (10%), esophagitis (20%), fatigue (12%), hyperglycemia (6%), nausea (16%), pulmonary symptoms (14%), sepsis (6%), and vomiting (16%). All other grade 3 to 4 hematologic and nonhematologic toxicities were uncommon (< 5%). CONCLUSION: Preoperative ODC plus RT is active and relatively safe in patients with locoregional esophageal cancer. Importantly, this therapy can be administered within 8 weeks. This regimen warrants additional study in this setting and in combination with newer biologic agents.
PURPOSE: Preoperative chemoradiotherapy is a primary treatment option for patients with resectable esophageal cancer. Combination regimens using newer agents may improve patient outcomes. This multicenter community-based phase I/II trial examined a modern triplet regimen comprised of oxaliplatin, docetaxel, and capecitabine (ODC) combined with radiation therapy (RT). PATIENTS AND METHODS: The primary end point was the pathologic complete response (pCR) rate. Eligibility criteria included resectable stage I to III cancer of the mid-/distal-esophagus or gastroesophageal junction, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Treatment included oxaliplatin 40 mg/m(2), docetaxel 20 mg/m(2) (intravenous, weekly x 5); capecitabine 1,000 mg/m(2) orally twice daily on days 1 to 7, 15 to 21, and 29 to 35; and concurrent RT (45 Gy). Resection was performed during weeks 9 to 12. ODC and RT safety was determined in a phase I portion (n = 10) preceding phase II. RESULTS: Fifty-nine patients were enrolled (September 2005 to February 2008; phase I/cohort 1, 10 patients; phase I/cohort 2/phase II, 49 patients). Baseline characteristics included median age of 63 years; 84% male; ECOG PS 0 and 1, 51% and 49%, respectively; adenocarcinoma and squamous cell, 69% and 18%, respectively; stage I, II, and III, 12%, 41%, and 45%, respectively. Phase I revealed no dose-limiting toxicity. Responses: pCR rate, 49%; objective response rate, 61% (24 complete and six partial responses); stable disease, 6%; and progressive disease, 2%. Sixty-nine percent of patients underwent surgery. Survival: median follow-up, 116 weeks; median disease-free survival (DFS) and overall survival (OS) were 16.3 and 24.1 months, respectively. Two-year DFS and OS were 45.1% and 52.2%, respectively. Most common (>or= 5%) grade 3 to 4 nonhematologic toxicities were anorexia (20%), dehydration (16%), diarrhea (8%), dysphagia (10%), esophagitis (20%), fatigue (12%), hyperglycemia (6%), nausea (16%), pulmonary symptoms (14%), sepsis (6%), and vomiting (16%). All other grade 3 to 4 hematologic and nonhematologic toxicities were uncommon (< 5%). CONCLUSION: Preoperative ODC plus RT is active and relatively safe in patients with locoregional esophageal cancer. Importantly, this therapy can be administered within 8 weeks. This regimen warrants additional study in this setting and in combination with newer biologic agents.
Authors: Matthew D Wood; Bassem I Zaki; Stuart R Gordon; John E Sutton; Mikhail Lisovsky; Jiang Gui; Jeffrey A Bubis; Konstantin H Dragnev; James R Rigas Journal: J Thorac Oncol Date: 2013-04 Impact factor: 15.609
Authors: Rifat Hasina; Mosmi Surati; Ichiro Kawada; Qudsia Arif; George B Carey; Rajani Kanteti; Aliya N Husain; Mark K Ferguson; Everett E Vokes; Victoria M Villaflor; Ravi Salgia Journal: J Carcinog Date: 2013-10-28