| General information |
| Database: | DB00396 |
| Objective: | Standard treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) is concurrent chemoradiation. Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor, which has shown activity in SCCHN.phase I study aims to determine the maximum tolerated dose and doselimiting toxicity (DLT) of adding erlotinib to chemoradiation therapy in patients with surgically resected locally advanced SCCHN. |
| Authors: | Arias de la Vega F, et al |
| Title: | Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICORphase I trial. |
| Journal: | Ann Oncol. |
| Year: | 2012 |
| PMID: | 21778302 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced squamous cell carcinoma of the head and neck |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Erlotinib and chemoradiation |
| Study Type: | doseescalatingphase I study |
| Key Patients Feature: | Patients with histological or cytological diagnosis of squamous cellcarcinoma of the oral cavity, oropharynx, larynx, or hypopharynx whohad been treated with surgical resection with curative intent were eligible.patients were required to have at least one of the following criteria:pT3-4 tumor stage (except T3N0 of the larynx with negative margins);pN2-3 nodal stage; or unfavorable pathological findings such asextranodal extension, positive resection margins, and perineural and/orvascular involvement. Other eligibility criteria included the following: age18-70 years old; life expectancy 12 months; Eastern CooperativeOncology Group (ECOG) performance status of zero to one; adequatebone marrow (absolute neutrophil count > 1.5 . 109/l, platelets > 100 .109/l and hemoglobin > 9 g/dl), liver [bilirubin < 1.5 .upper limit ofnormal (ULN), alkaline phosphatase, aspartate transaminase and alaninetransaminase < 3.0 . ULN], and renal function (calculated creatinineclearance > 60 ml/min or serum creatinine < 1.5 . ULN). Women ofchildbearing potential were required to have a negative pregnancy testwithin 48 h of study enrollment. In addition, fertile male and femalepatients were required to use appropriate contraceptive methods.Patients needed to be able to swallow pills or have a functioninggastrostomy tube. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Study designdoseescalatingphase I study with three cohorts of three to six patients each that received increasing doses of erlotinib (100150 mg/day p.o.) and cisplatin (3040 mg/m(2) i.v., day 1) for 7 weeks. Radiotherapystandard regimen of 1.8 Gy daily (5 fractions/week) to a maximum total dose of 63 Gy in 7 weeks. |
| Primary End Point: | the maximum tolerated dose (MTD) |
| Secondary End Point: | to quantify the main toxic effects of the combination |
| Patients Number: | 13 |
| Trial Results |
| DLT_MTD: | the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m2) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. Recommended dose foradditional studies: erlotinib 150 mg/day p.o.; cisplatin 30 mg/m2/week i.v. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Overall, the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m2) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. |
| Conclusions: | Erlotinib can be safely combined with chemoradiation without requiring dose reduction of chemo or radiotherapy in this postsurgical population. |