Expression of telomerase enzyme as predictive factor of response to first line chemotherapy with gemcitabine/carboplatin in advanced non-small cell lung cancer (IIIB and IV)

Abstract

17156 Background: Non-small cell lung cancer (NSCLC) is the most frequent neoplasia in the world and the main cause of death for cancer. The palliative chemotherapy is the elected treatment for patients in stage III and IV. The telomerase enzyme is expressed in 82% of neoplasias and its activity is implied in the genomic instability, apoptosis inhibition and cell immortalization. Objective: To determine the predictive value of the expression of the telomerase enzyme with the first line regimen gemcitabine (1 gr/m2 SC, days 1 and 8) and carboplatino (AUC of 5 in day 1) every 28 days in patients with NSCLC clinical stages IIIB and IV. The response and toxicity rate was also determined. Methods: Patients were recruited in a period between 04/01/2004 and 11/30/2004, ages between 18 and 80, ECOG ≤ 2, measured disease (RECIST), virgin to treatment, permissible hematic biometry for chemotherapy and optimal kidney function. A total of 17 patients with an average age of 61 (range 44 to 77 years old) 9/17 (53%) males and 8/17 (47%) females, 4/17 with clinical stage IV (23%) and 13/17 with clinical stage IIIB (77%) from which: 8/13 (61%) presented pleural effusion. From the total number of patients, 1/17 presented ECOG 0 (6%), 14/17 ECOG 1 (82%) and 2/17 ECOG 2 (12%). The histopathologic diagnosis was adenocarcinoma in 12/17 (70%) and epidermoid carcinoma in 5/17 (30%). A rabbit polyclonal antibody was used to asses the expression of the telomerase enzyme by the immunohistochemical method. Results and Conclusions: It was demonstrated in 11/17 patients that the high expression of telomerase enzyme is directly correlated to the lack of response to treatment (3/11 patients stable disease and 4/11 with progressive disease); and a low or absent expression (4/11 patients) was correlated to a response higher than 30% (p = 0.045). The obtained response rate was lower that the previous ones reported with the regimen gemcitabine (days 1, 8 every 21 days and 1, 8 and 15 every 28 days) presenting a minimum hematologic toxicity. This analysis suggests that the telomerase enzyme could be a response predictive marker in the NSCLC with this therapeutic regimen. No significant financial relationships to disclose.