| General information |
| Database: | DB00350 |
| Objective: | Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. They conducted a pilotphase II study of a new combinedmodality paradigm of targeted therapy (cetuximab) with chemoradiotherapy. |
| Authors: | Pfister DG, et al |
| Title: | Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilotphase II study of a new combinedmodality paradigm. |
| Journal: | J Clin Oncol. |
| Year: | 2006 |
| PMID: | 16505426 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced squamous cell cancer of the head and neck without distant organ metastases |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy |
| Study Type: | singleinstitution, openlabel, singlearm pilotphase II |
| Key Patients Feature: | 18 years or older with histologically proven, stageIII or IV, M0, 32 new or recurrent SCCHN. Measurable or assessable diseasewas required. Additional inclusion criteria were as follows: Karnofsky performance status of 60%, adequate hematologic function (WBC count 3, 000/ L, granulocytes 1, 500/ L, hemoglobin 9 g/dL, and plateletcount 100, 000/ L), adequate liver function (total bilirubin 1.5 theupper limit of normal and alkaline phosphatase and AST 2.5 the upperlimit of normal), adequate renal function (creatinine 1.5 mg/dL or calculated creatinine clearance 60 mL/min), and serum calcium 11.5 mg/dL |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10). |
| Primary End Point: | safety and tolerability; |
| Secondary End Point: | the PK, the best overall response, the time to progression and overall survival time; |
| Patients Number: | 22 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Of the 16 patients assessable for response, 15 had a major response(two CRs and 13 PRs), and one patient had progression ofdisease, yielding a response rate of 94% (95% CI, 70% to 100%). |
| Disease Control Rate: | the 3year locoregional control rate is 71%. (95% CI, 52% to 91%) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | the 3year progression free survival rate is 56% (95% CI, 35% to 78%) |
| Median OS A vs. C: | the 3year overall survival rate is 76%(95% CI, 58% to 94%) |
| Adverse Event(agent arm): | Grade 3 or 4 cetuximabrelated toxicities included acnelike rash (10%) and hypersensitivity (5%). however, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. |
| Conclusions: | This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. Hotheyver, preliminary efficacy is encouraging, and further development of this targeted combinedmodality paradigm is warranted. |