title: Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant esophageal squamous cell carcinoma patients: results of a pilot study.
abstract: Concurrent chemoradiotherapy is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, a number of patients present intolerance to chemoradiotherapy because of advanced age or malnutrition. Erlotinib, an inhibitor of epidermal growth factor receptor tyrosine kinase, was shown to be effective in treating esophageal carcinoma, with mild toxicities. In this pilot study, we investigated the safety and efficacy of concurrent erlotinib and radiotherapy as an alternative treatment modality for esophageal carcinoma patients who are intolerant to chemoradiotherapy. Pathologically diagnosed esophageal squamous cell carcinoma patients who could not tolerate concurrent chemoradiotherapy were enrolled. All patients were treated with concurrent erlotinib and intensity-modulated radiation therapy. Erlotinib was given orally for 60 days (150 mg per day). Radiotherapy (total dose, 60 Gy) was given at dosages of 2 Gy for a total of 30 times. Immunohistochemical staining was performed to assess epidermal growth factor receptor expression. Toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). The overall survival, progression-free survival, and local-regional relapse-free survival were calculated using the Kaplan-Meier method. Between December 2007 and March 2011, 18 patients were enrolled. The median age was 71.5 years. Primary disease was stages II, III, and IV in 3, 8, and 4 patients, respectively. There were three patients with recurrent disease after radical surgery. The median follow-up time was 17.2 months. Grade 3 esophagitis and skin rash were observed in five (27.8%) and two (11.1%) patients, respectively. Radiation pneumonitis of grades 2 and 5 was observed in one patient each. No grade 3/4 impaired liver function or hematological toxicity was observed. At 1 month after radiotherapy, two (11.1%) patients achieved complete response, 11 (61.1%) patients achieved partial response, and 5 (27.8%) patients had stable disease. The median time of overall survival and progression-free survival was 21.1 and 12 months, respectively. Two-year overall survival, progression-free survival, and local-regional relapse-free survival were 44.4%, 38.9%, and 66.7%, respectively. Five of six patients examined for epidermal growth factor receptor had high expression levels (3+). The relationship between epidermal growth factor receptor expression and treatment outcomes could not be concluded. For esophageal squamous cell carcinoma patients who cannot tolerate chemoradiotherapy, concurrent erlotinib and radiotherapy are tolerable and effective. Valuable markers to predict the effect of erlotinib should be exploited in future studies.
authors.affiliation: Department of Radiation Oncology, Cancer Hospital and Institute, Peking Union Medical College and Chinese Academy of Medical Science, 100021, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhai
authors.forename: Z
authors.initials: Z
authors.lastname: Hui
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Zou
authors.forename: J
authors.initials: J
authors.lastname: Liang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Lv
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: L
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D066246:ErbB Receptors / Q000032:analysis; D000069347:Erlotinib Hydrochloride; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D004941:Esophagitis / Q000209:etiology; D005076:Exanthema / Q000209:etiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D017564:Radiation Pneumonitis / Q000209:etiology; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors