| General information |
| Database: | DB00395 |
| Objective: | Erlotinib, an orally active selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has synergistic activity with radiation and with cisplatin. The EGFR is overexpressed in the majority of head and neck cancers. The primary objective of thisphase I study was to determine the maximumtolerated dose (MTD) of erlotinib in combination with lowdose daily cisplatin and radiotherapy. They also sought evidence of biologic activity of erlotinib alone using serial 18FDG positron emission tomography (PET) imaging. |
| Authors: | Gilbert J, et al |
| Title: | a phase I trial of erlotinib and concurrent chemoradiotherapy for stage III and IV (M0) squamous cell carcinoma of the head and neck. |
| Journal: | Clin Cancer Res |
| Year: | 2012 |
| PMID: | 22271880 |
| Trial Design |
| Clinical Trial Id: | NCT00049166 |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced squamous cell cancer of the head and neck without distant organ metastases |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | erlotinib and concurrent chemoradiotherapy |
| Study Type: | Phase I Trial |
| Key Patients Feature: | a new diagnosis of histologically confirmed AJCC StageIII (T3N01) or IV (T14N23M0, T4N0M0) squamous cell carcinoma of the oral cavity ororopharynx. Other criteria included: no prior therapy for the SCCHN; no diagnosis of othermalignancy within the prior 3 years; age more than and equal to 18 years; ECOG PS 0-2; adequate organ andmarrow function as denoted by ANC more than and equal to 1500/mm3, platelets more than and equal to 100, 000/mm3, total bilirubinwithin institutional upper limit of normal (ULN), transaminases < 2.5x ULN, creatininewithin ULN or creatinine clearance more than and equal to 60 mL/min/1.73 m2. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Oral erlotinib was taken daily starting with a 14day runin and continued until radiation therapy (RT) was completed. Lowdose daily cisplatin, 6 mg/m(2) i.v. was given concurrently with standard fractionation RT to a total dose of 66 to 70 Gy. Dose escalation followed a modified Fibonacci dose escalation design. |
| Primary End Point: | the MTD and the DLT. |
| Secondary End Point: | NA |
| Patients Number: | 22 |
| Trial Results |
| DLT_MTD: | A Dose Limiting Toxicity (DLT) was defined as the following: grade 3 or 4 neutropenia associated with fever or neutropenia lasting longer than 5 days; grade 3 or 4 thrombocytopenia; any grade 3 or 4 nonhematological toxicity per NCI/CTC criteria with the exception of grade 4 mucositis that resolves to grade 2 or less with a treatment break not to exceed 10 days.Two other patients were withdrawn from protocol without experiencing DLT. One patient was, diagnosed with Fanconi¡¯s anemia (n=1), and another had a diagnosis of metastatic disease by PET on day 14. These three patients were subsequently replaced on study.MTD of the combination of erlotinib, cisplatin and radiation therapy was not reached. |
| Objective Response Rate: | Thus, overall response rate derived from tumor measurements based on imaging studies was 83% for all dose levels combined. Response evaluation took place at an average of 83 days post CCR (range 64-194 days). |
| 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): | the common Aes contain: Nausea, Anorexia, Xerostomia, Pneumonitis, Diarrhea, Lymphopenia, Mucositis, Radiation dermatitis and Rash. |
| Conclusions: | Erlotinib in combination with lowdose daily cisplatin and RT is well tolerated and shows evidence of clinical efficacy. The combination should be evaluated further. |