| General information |
| Database: | DB00399 |
| Objective: | Erlotinib, an oral tyrosine kinase inhibitor, is active against headandneck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. They investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. |
| Authors: | Herchenhorn D, et al |
| Title: | Phase I/II study of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck. |
| Journal: | Int J Radiat Oncol Biol Phys. |
| Year: | 2010 |
| PMID: | 20421154 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advacned oropharynx, larynx, or hypopharynx squamous cell carcinoma without metastasis |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | erlotinib combined with cisplatin and radiotherapy |
| Study Type: | PHASE I/II STUDY |
| Key Patients Feature: | Eligible patients were aged 18 years or older with histologicallyproven American Joint Committee on Cancer (22) Stage III/IV, M0, oropharynx, larynx, or hypopharynx squamous cell carcinoma.Patients must have been considered ineligible for primary surgicaltherapy in the judgment of a headandneck surgeon (impossibilityto achieve negative surgical margins without unacceptable functional/cosmetic results) or if a permanent tracheotomy precludingorgan preservation was required. Other inclusion criteria were measurable disease, no prior antineoplastic therapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, an estimatedcreatinine clearance greater than 50 mL/min, and normal hematologic and liver function tests. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | 100 mg/m(2) of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. Duringphase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. |
| Primary End Point: | DLT, the recommendedphase II dose, and toxicity, 3year PFS and OS rates. |
| Secondary End Point: | NA |
| Patients Number: | 37 |
| Trial Results |
| DLT_MTD: | Nodoselimiting toxicity occurred inphase I, and the recommended phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and infield dermatitis, acneiformrash, and diarrhea. |
| Objective Response Rate: | 31 patients receiving a 150mg daily dose of erlotinib, 23 (74%; 95% confidenceinterval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residualdisease, and 1 died of sepsis during treatment |
| Disease Control Rate: | 0.74 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | the 3year progression free survival rate: 61% |
| Median OS A vs. C: | the 3year overall survival rate: 72% |
| Adverse Event(agent arm): | The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and infield dermatitis, acneiform rash, and diarrhea. |
| Conclusions: | This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC. |