Tumor markers have widespread use in oncology. Potential clinical applications of tumor markers are: facilitate the early diagnosis, offer a guide for the evaluation of prognosis, help in selecting patients for adjuvant chemotherapy, help in assessing the response to therapy and in diagnosis of early relapses. Moreover the serum level of an ideal marker should: increase pathologically in the presence of a neoplasm (high sensitivity), not increase in the absence of neoplasm (high specificity), relate to tumor burden and metastatic spread, change in accordance with the clinical evolution, reflecting the current status of disease. There are many efforts for reaching the ideal tumor marker in oncology. Tumor associated antigen such as carcinoembryogenic antigen (CEA), tissue polypeptide antigen (TPA), squamous carcinoma antigen (SCC-Ag), other polypeptide antigen such as ferritin, soluble interleukin 2 receptors (sIL- 2r), chromogranin A, enzymes such as, neuron specific enolase (NSE), creatine phosphokinase-BB (CPK-BB), glycosyl transferases and hormones such as bombesin/gastrin releasing peptide (BN/GRP), adrenocorticotropin (ACTH), antidiuretic hormone (ADH), calcitonin (CT), insulin like growth factor (IGF I and II) have been investigated in patients with lung cancer [9
NSE is the most useable tumor marker in lung cancer patients with small cell histology. NSE is the neurol isoenzyme of the intracytoplasmic enzyme enolase, which was first found in the extract of brain tissue and was later shown to be present in neuroendocrine cells and tumors. Elevated serum concentrations of NSE have been found in over 70% of patients with SCLC. In general, studies noted that NSE levels are higher in the patients with extensive stage than limited stage [11-13]. In our study, tumor marker levels were classified as elevated or not elevated. NSE was elevated in 77.6%, CEA in 47.9%, ferritin in 45.8%, LDH in 22.9%. Concentration of NSE in serum was higher with statistically significant difference in extensive disease than limited disease. The serum NSE levels are associated with stage and reflect the tumor burden. After treatment NSE levels decreased significantly in all patients with limited stage disease. NSE levels in patients with extensive stage didn’t decrease significantly. Patients with extensive stage had bad prognosis and combination chemotherapy was less effective than limited stage. Therefore tumor markers could not reflect the response to therapy.
We determined that patients whose NSE levels were not elevated had higher response rate than patients with elevated NSE levels but this difference was not statistically significant. Median progression-free and overall survival times in patients with normal NSE levels were superior to patients with elevated NSE levels. One-year survival rate was also superior in the patients whose NSE levels were not elevated, but 2-year survival rate was similar. Many studies examined the prognostic significance of serum NSE in patients with SCLC [5,14]. Jorgersen at al.  showed in 770 patients that NSE was the most powerful predictor of survival followed by performance status and stage of disease. Bonner et al.  showed that both pretreatment NSE and treatment induced minimum NSE were independent prognostic predictors of time to progression and survival.
We studied serum tumor markers in patients who were treated with combination of cylophosphamide, epirubicin and vincristine. NSE is correlated with stage and decrement after treatment significantly. NSE levels may play a role as prognostic and predictive factor in patients who were treated with this combination. Although there are many data in the literature about CEA, ferritin, and LDH that are used as biomarkers in patients with SCLC, we did not find any correlation in our patients who were treated with this combination [6,7,16,17]. Comparison of patients who did and did not receive low molecular weight heparin has not revealed further significant results for NSE, CEA, ferritin and LDH. Receiving low molecular weight heparin didn’t affect results of tumor markers analysis. In conclusion; NSE was the most reliable tumor marker in small cell lung cancer patients who were treated with combination of cylophosphamide, epirubicin and vincristine. NSE was in correlation with stage and reflected the response to therapy in patients who were treated with this regimen.