| General information |
| Database: | DB00343 |
| Objective: | Radiotherapy (RT) combined with cisplatin or cetuximab is the standard of care for patients with locally advanced head/neck cancer (LAHNC). The feasibility of radiochemotherapy with cisplatin and cetuximab, supported with amifostine, was herein investigated. |
| Authors: | Koukourakis MI, et al |
| Title: | Radiochemotherapy with cetuximab, cisplatin, and amifostine for locally advanced head and neck cancer: a feasibility study. |
| Journal: | Int J Radiat Oncol Biol Phys. |
| Year: | 2010 |
| PMID: | 19744802 |
| 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: | Radiochemotherapy with cetuximab, cisplatin, and amifostine |
| Study Type: | prospectivephase II study |
| Key Patients Feature: | Inclusion criteria consisted of patients older than 18 years, a goodperformance status, as well as a normal hematological and biochemical blood status at the time of entry into the study. Only patientswith carcinomas (including salivary gland carcinomas) entered thestudy. Other criteria were medical suitability for definitive radiotherapy and no previous chemotherapy or radiotherapy within the last 3years. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Conformal hypofractionated/accelerated RT with amifostine cytoprotection (2.7 Gy/fraction, 21 fractions in 4 weeks) was combined with cisplatin (30 mg/m(2)/week) and cetuximab (standard weekly regimen) therapy. The dose of amifostine was individualized according to tolerance. |
| Primary End Point: | feasibility and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 43 |
| Trial Results |
| DLT_MTD: | A high daily amifostine dose (750-1, 000 mg) was tolerated by 41.8% of patients, and a standard dose (500mg) was tolerated by 34.9% of patients. A high amifostine dose was linked to reduced RT delays (p = 0.0003). Grade 3 to 4 (34) mucositis occurred in 7/43 (16.2%) patients, and fungal infections occurred in 18/43 (41.8%) patients |
| Objective Response Rate: | Complete response was noted in 24/35(68.57%) patients, partial response in 8/35 (22.85%) patients, and stable disease in 3/35 (8.58%) patients |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 24 month overall survival rate was 91%. |
| Adverse Event(agent arm): | Patients receiving 750 to 1, 000 mg of amifostine experienced a lotheyr incidence of grade 34 mucositis (1/18 vs. 6/25 patients), but the difference did not reach significance (p= 0.10). The fungal infection was common in all groups. Cetuximab related acneiform rash was the main side effect of chemotherapy. Grade 2 extensive rash of the face and upper trunk demanding medical therapy was noted in 9/43 (20.9%) patients, while grade 3 rash with extensive desquamation, pain, and disfigurement was noted in 1/43 (2.3%) patients (combined grade 2 and 3, 10/43 [23.3%] patients). Out of 11 patients treated for laryngeal/epilaryngeal cancer, 1 (9%) patient developed laryngeal edema grade 4 (diffuse laryngeal edema with narrowing of the airway by >50%). Two out of 6 (33%) patients with hypopharyngeal cancer developed grade3 cervical stricture. Fibrosis grade 2 of neck tissues was noted in 4/43 (9.3%) cases. No tissue necrosis was noted. |
| Conclusions: | In this feasibility study, weekly administration of cisplatin and cetuximab was safely combined with accelerated RT, supported with amifostine, at the cost of a high incidence of acneiform rash but a reduced incidence of amifostinerelated feverrash. A high daily dose of amifostine allows completion of therapy with minor delays. |