title: Preoperative chemoradiation therapy in combination with panitumumab for patients with resectable esophageal cancer: the PACT study.
abstract: OBJECTIVE
  Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer.
  
  
  METHODS
  Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m(2)) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR.
  
  
  RESULTS
  From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response.
  
  
  CONCLUSIONS
  The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: s.kordes@amc.uva.nl.
authors.forename: Sil
authors.initials: S
authors.lastname: Kordes
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mark I
authors.initials: MI
authors.lastname: van Berge Henegouwen
authors.affiliation: Department of Radiotherapy, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Hulshof
authors.affiliation: Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jacques J G H M
authors.initials: JJ
authors.lastname: Bergman
authors.affiliation: Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: van der Vliet
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kapiteijn
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hanneke W M
authors.initials: HW
authors.lastname: van Laarhoven
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Richel
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jean H G
authors.initials: JH
authors.lastname: Klinkenbijl
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sybren L
authors.initials: SL
authors.lastname: Meijer
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Wilmink
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D000077544:Panitumumab; D011300:Preoperative Care / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077544:Panitumumab; D016190:Carboplatin; D066246:ErbB Receptors; D017239:Paclitaxel