| General information |
| Database: | DB00338 |
| Objective: | To present the first report of a phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary headandneck cancer (HNC). |
| Authors: | Rusthoven KE, et al |
| Title: | Initial results of a phase I doseescalation trial of concurrent and maintenance erlotinib and reirradiation for recurrent and new primary headandneck cancer. |
| Journal: | Int J Radiat Oncol Biol Phys. |
| Year: | 2010 |
| PMID: | 20231078 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | recurrent or a new primary headandneckcancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | concurrent and maintenance erlotinib and reirradiation |
| Study Type: | prospectivephase I doseescalation study |
| Key Patients Feature: | Adult patients with a recurrent or a new primary headandneckcancer previously treated with radiation therapy were eligible. Therecurrent or the new primary tumor had to be surgically unresectable, or surgically resectable but the patient declined surgery, or surgerywas attempted but left the patient with gross residual disease. The interval since the completion of the previous course of radiation wasrequired to be at least 6 months. Greater than 50% of the recurrentor new primary tumor volume had to have received at least 45 Gyin the initial radiation course. The initial radiation dose must nothave exceeded a maximum dose of 75 Gy. All patients had tohave a Karnofsky performance status of greater than 60 and havenormal kidney, liver, and bone marrow function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. |
| Treatment Info: | patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinib started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or doselimiting toxicity. |
| Primary End Point: | toxicity(DLT, MDT). |
| Secondary End Point: | NA |
| Patients Number: | 14 |
| Trial Results |
| DLT_MTD: | A DLT developed in 1 patient. This patient was treated inCohort III. The patient presented with a Level II cervicallymph node recurrence 22 months after completing IMRT |
| Objective Response Rate: | Information regarding treatment response was availablefor 12 of 13 patients. Among the 11 patients with recurrentor new primary tumor in the headandneck mucosa, 9 patients(82%) had complete response, 1 patient (9%) had stabledisease, and 1 patient (9%) had disease progression |
| Disease Control Rate: | 0.91 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median progression free survival and the 1year progression free survival were 7.8 months and 38%, respectively. |
| Median OS A vs. C: | Median survival was 15.0 months, and the 1year survival rate was 58%. |
| Adverse Event(agent arm): | One patient had a doselimiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinibrelated toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. |
| Conclusions: | Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible. |