| General information |
| Database: | DB00417 |
| Objective: | The specific aims of the study were to evaluate the 2year overall survival (OS) and progression free survival (PFS), toxicity profile, and best objective response rate in patients with locally advanced, clinically unresectable esophageal cancer receiving cetuximab, cisplatin, irinotecan, and thoracic radiotherapy (TRT) within a multiinstitutional cooperativegroup setting. |
| Authors: | Tomblyn MB, et al |
| Title: | Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phaseII study of the SWOG (S0414). |
| Journal: | J Thorac Oncol. |
| Year: | 2012 |
| PMID: | 22481235 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer and esophagusgastroesophageal junction cancer |
| Cancer Subtype: | squamous cell carcinoma or adenocarcinoma of the thoracic esophagus or gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy |
| Study Type: | phase II study of the SWOG |
| Key Patients Feature: | Eligible patients had pathologically documented squamous cell carcinoma oradenocarcinoma of the thoracic esophagus (more than and equal to 20 cm from the incisors) or gastroesophageal(GE) junction, and all had measurable or evaluable cT4 M0 or unresectable disease. History, physical examination, EUS or EGD, chest radiography, PET scans with CT or MRI, as wellas adequate renal and hepatic function, absence of prior cancer, absence of prior hemotherapy or radiotherapy, Zubrod performance status 0-2, and IRBapproved informedconsent were all required. A baseline EKG and pulmonary function studies wererecommended. Bronchoscopy with negative cytology was required for patients with aprimary tumor < 26 cm from the incisors. Patients with clinical evidence of tracheoesophageal fistulas were ineligible for this trial. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were to receive four 21day cycles of cetuximab 400 mg/m (day 1, cycle 1), cetuximab 250 mg/m (day 8, 15, cycle 1; then days 1, 8, and 15 for subsequent cycles), cisplatin 30 mg/m (days 1 and 8, all cycles), and irinotecan 65 mg/m (days 1 and 8, all cycles). TRT was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, to begin with on day 1 of cycle 3. |
| Primary End Point: | 2year OS; |
| Secondary End Point: | assessment of the toxicity profile of this regimen, best objective response to therapy, and progression free survival. |
| Patients Number: | 21 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The overall response rate (95% CI) among 17 evaluable patients was 17.6% (3.843.4%), including 6% confirmed complete responders and 12% unconfirmed partial responders. Two deaths resulted from protocol treatment (sudden death and gastrointestinal necrosis). |
| Disease Control Rate: | 0.18 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6.4 (3.7-12.0) months |
| Median OS A vs. C: | 11.2 (6.4-43.6) months |
| Adverse Event(agent arm): | Two deaths were due to protocol treatment (sudden death & GI necrosis). Ten (47.6%) and 6 (28.6%) patients had Grade 3/4 toxicity, respectively: 52.4% hematologic, 23.8% fatigue, 19.0% nausea, 19.0% dehydration, and 19.0% anorexia. |
| Conclusions: | Concomitant cetuximab, cisplatin, irinotecan, and TRT they were poorly tolerated in the first North American cooperative group trial testing this regimen for locally advanced esophageal cancer as treatmentrelated mortality approached 10%. SingleinstitutionphaseII cetuximabbased combined modality trials have yielded encouraging results in preliminary analyses. The SWOG GI Committee endorses enrollment to open clinical trials to clarify the therapeutic ratio of cetuximabbased combined modality approaches for esophageal cancer. |