| General information |
| Database: | DB00421 |
| Objective: | This multicenterphase IB/II trial investigated cetuximab added to preoperative chemoradiotherapy for esophageal cancer. |
| Authors: | Ruhstaller T, et al |
| Title: | Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenterphase IB/II Trial (SAKK 75/06). |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21205757 |
| Trial Design |
| Clinical Trial Id: | NCT00445861 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | squamous cell carcinoma or adenocarcinoma of the thoracic esophagus and the gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 6 |
| Therapeutic Combination Content: | Cetuximab + chemoradiotherapy before surgery |
| Study Type: | multicenterphase IB/II trial |
| Key Patients Feature: | reviously untreated patients with histologically confirmed squamouscell carcinoma or adenocarcinoma of the thoracic esophagus and the gastroesophageal junction (Sietheyrt type I) were included in this prospective multicentertrial.Patientswereeligibleifthetumorwaslocallyadvancedbutdeemedresectable by a multidisciplinary team (stage T3N0, T13N , or T4Nx, iftechnically resectable) and if no metastases (including cervical or celiac lymphnode involvement [M1a]) were detected in any of the pretreatment examinations, which consisted of upper endoscopy, endoscopic ultrasonography(EUS), helical computed tomography (CT) scans of the chest and abdomen, positron emission tomography (PET) scan or combined PETCT scan, andbronchoscopy if airway infiltration was suspected. Laparoscopy for tumors ofthe lotheyr third of the esophagus was optional. Other eligibility criteria included age 18 to 70 years, WHO performance status 0 to 1, and adequatehematologic, renal, and hepatic function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received two 3week cycles of induction chemoimmunotherapy (cisplatin 75 mg/m(2) day 1, docetaxel 75 mg/m(2) day 1, cetuximab 250 mg/m(2) days 1, 8, 15 [400 mg/m(2) loading dose]) followed by chemoimmunoradiation therapy (CIRT) and surgery. CIRT consisted of 45 Gy radiotherapy (RT) plus concurrent cisplatin 25 mg/m(2) and cetuximab 250 mg/m(2) weekly for 5 weeks in cohort 1. If fetheyr than three of seven patients experienced limiting toxicity (LT), the next seven patients also received docetaxel (20 mg/m(2) weekly ¡Á 5). If fetheyr than three patients experienced LTs, 13 additional patients were treated at this dose. |
| Primary End Point: | protocoldefined limiting toxicity (LT) during chemoimmunoradiation (CIRT). |
| Secondary End Point: | feasibility and efficacy of the entire multimodal therapy in the communitybased setting. |
| Patients Number: | 28 |
| Trial Results |
| DLT_MTD: | During CIRT, no LT occurred, rash was not exacerbated withinthe RT field, and the main grade 3 toxicities were esophagitis (seven patients), anorexia (three), fatigue(three), and thrombosis (two). Surgery (R0 resection) was performed in 25 patients |
| Objective Response Rate: | Of the 25 patientswhounderwentsurgery, pathologic responses were observed in 12 of 14 patients withadenocarcinoma (86%; 95% CI, 57% to 98%) and in 7 of 11 patientswith squamous cell carcinoma (64%; 95% CI, 31% to 89%; Table 4) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Overall survival rates at 6 and 12 months were 96% (95% CI, 90% to 100%) and 86% (95% CI, 73% to 100%), respectively. |
| Adverse Event(agent arm): | The main grade 3 to 4 toxicities during CIRT consisted of esophagitis/dysphagia (grade 3 in seven patients; 26%). A deterioration in renal function led to a switch from cisplatin to carboplatin in two patients during CIT and in one patient during CIRT. An additional patient switched from cisplatin to carboplatin because of hearing impairment after the first cycle of CIT. No treatmentrelated deaths occurred. Infections were the predominant complication of surgery and occurred in 10 patients (40%). Three patients (12%) developed anastomotic leakage, which required repeated surgery in one patient but resolved with conservative measures in the other two patients. There were no deaths at 30 days post surgery. Furthermore, after a followup of 1 year, there was no inhospital mortality, and there were no treatmentrelated deaths. |
| Conclusions: | Adding cetuximab to preoperative chemoradiotherapy is feasible without increasing postoperative mortality.phase III investigation has begun based on the high histopathologic response and R0 resection rate. |