| General information |
| Database: | DB00331 |
| Objective: | The objective of thisphase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integratedboost (SIB), intensitymodulated radiation therapy (IMRT) into a well described 5fluorouracil (5FU) and hydroxyurea (HU)based chemoradiation regimen. |
| Authors: | Kao J, et al |
| Title: | Phase 2 trial of concurrent 5fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensitymodulated radiation therapy for locally advanced head and neck cancer. |
| Journal: | Cancer. |
| Year: | 2011 |
| PMID: | 20830768 |
| Trial Design |
| Clinical Trial Id: | NCT00462735 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | Advanced Head and Neck Cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | concurrent 5fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensitymodulated radiation therapy |
| Study Type: | Phase II Trial |
| Key Patients Feature: | Eligible patients had eitherHNSCC or poorly differentiated carcinoma. Patients hadeither stage IVA and IVB disease or highrisk stage III disease according to the sixth edition of the American JointCommittee on Cancer (AJCC) Cancer Staging Manual, which was defined as a base of tongue or hypopharyngealprimary tumor, or major pathologic risk factors (microscopic positive margins or extracapsular extension). Allcases were revietheyd at a multidisciplinary conference, which was attended by representatives from the Departments of Head and Neck Surgery, Radiation Oncology, Medical Oncology, Palliative Care, Social Work, andNutrition. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | SIBIMRT was prescribed to lowrisk volumes (43.2 gray [Gy] to 48 Gy) and intermediaterisk volumes (5463 Gy). A separate IMRT conedown plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 6072 Gy) administered in 1.5 Gy fractions twice daily during weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5FU (600 mg/m2), HU (500 mg twice daily), and cetuximab (250 mg/m2). |
| Primary End Point: | Feasibility and Tolerability;Survival and Patterns of Failure;LongTerm Toxicity;Quality of Life |
| Secondary End Point: | NA |
| Patients Number: | 33 |
| Trial Results |
| DLT_MTD: | Grade 3 toxicity consistedof mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients there were no acute or late grade 4 adverse events |
| Objective Response Rate: | At a median followup of 24 months, the 2year rates of locoregional control, distantcontrol, diseasefree survival, and overall survival were 83%, 79%, 69%, and 86%, respectively |
| Disease Control Rate: | The 2year locoregional control, distant control rates were 83%, 79% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The 2year diseasefree survival rate: 69%. |
| Median OS A vs. C: | The 2year overall survival rate: 86%. |
| Adverse Event(agent arm): | Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade 4 adverse events. |
| Conclusions: | The current results indicated that concurrent 5FU, HU, and cetuximab plus SIBIMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer. |