| General information |
| Database: | DB00332 |
| Objective: | Intensification of chemoradiation for advanced head and neck squamous cell carcinoma (HNSCC) is unlikely due to toxicity. Cetuximab combined either with radiotherapy or with chemotherapy showed favourable toxic profile with positive results in both combinations. Therefore, cetuximab could intensify chemoradiation without worsening toxicity. They conducted a phase II study of chemoradiation and cetuximab. |
| Authors: | Merlano M, et al |
| Title: | Cisplatinbased chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study. |
| Journal: | Ann Oncol. |
| Year: | 2011 |
| PMID: | 20810547 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Cisplatinbased chemoradiation plus cetuximab |
| Study Type: | a phase IIclinical study |
| Key Patients Feature: | Enrolled patients were required to have hystologically confirmed HNSCC oforal cavity, larynx, oropharynx or hypopharynx; age of 18 years or more;adequate liver (total bilirubin <1.5 . upper normal limit, alkalinephosphatase and aspartate aminotransferase <2.5 . upper normallimit), kidney (creatinine <1.3 mg/dl) and bone marrow (white bloodcell 3000/ll, granulocytes 1500/ll, platelet count 100 000/ll andhaemoglobin 9 g/dl) function; Eastern Cooperative Oncology Groupperformance status 0 or 1 and stage III or IVa to b with measurable lesions(AJCC staging system, sixth edition |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Treatment consisted of three cycles of cisplatin (20 mg/m(2)/day ¡Á 5 days) and fluorouracil (200 mg/m(2)/day ¡Á 5 days) rapidly alternated to three split courses of radiotherapy up to 70 Gy and concurrent weekly cetuximab. |
| Primary End Point: | complete response (CR) rate. |
| Secondary End Point: | toxicity, progression free survival (PFS) and overall survival (OS). |
| Patients Number: | 45 |
| Trial Results |
| DLT_MTD: | Acute grade3-4 toxic effects were in the expected range, but grade 3 radiodermatitis occurred in 33 patients. |
| Objective Response Rate: | CR occurred in 32 patients (71%). PFS and OS was 21+ months and 32.6+, respectively |
| Disease Control Rate: | 0.911 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 21+ months |
| Median OS A vs. C: | 32.6+ months |
| Adverse Event(agent arm): | Total parenteral nutrition was required in 22 patients (49%), with median duration 30.5 days (5-90). Four patients (8%) received enteral nutrition. Painful dysphagia (9% grade 2 and 7% grade 3) most likely was responsible for two fatal cases of aspiration pneumonia. Radiodermatitis occurred in all patients. |
| Conclusions: | The combination of cetuximab, cisplatin, fluorouracil and radiotherapy leads to a very high proportion of CR and it is feasible with toxic effects similar to those expected by radiochemotherapy. The only unexpected toxicity was skin toxicity grade 3 radiodermatitis occurred in 73% of the patients. |