Objective: In an era of ever evolving, promising new therapies for advanced non small cell lung cancer (NSCLC), early predictors of response to therapy, are needed. We evaluated early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods: 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer (Elecsys 2000; Roche Diagnostics). Response was evaluated using Response evaluation criteria in solid tumors (RECIST) criteria. Results: 10 patients had partial response, 9 patients had stable disease and 9 had progressive disease. None of the patients had complete response. 21/29 (72%) patients had an elevated baseline value of CYFRA 21-1. 62% pa- tients (18/29) had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was ir- respective of whether baseline value was normal or not. The average reduction was statistically significant (P = 0.002; 95% CI, from 0.8369 to 3.49464; t test). 8 out of 10 (80%) patients with partial response had a reduction in their 2nd reading of. CYFRA (P = 0.019; 95% CI, from 0.81965 to 7.20035; t test) which was significant. We also observed that 6/9 (66%) patients whose disease remains stable also had a decrease in their subsequent reading (P = 0.0106; 95% CI, from –0.44942 to 3.82720; t test), though it was not significant statistically. Although 5 out of 9 (55%) patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statistically significant (P = 0.537; 95% CI, from –1.20021 to 2.13354; t test). 14 out of 19 (73%) who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21-1 and was significant statistically (P = 0.004; 95% CI, from 0.74792 to 3.50208; t test). We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease (P = 0.001), which was statistically significant. Conclusion: We can conclude that monitoring of serum marker CYFRA 21-1, early during first-line chemotherapy may be a useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC. Objective: In an era of ever evolving, promising new therapies for advanced non small cell lung cancer (NSCLC), early predictors of response to therapy, are needed. We assessed early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods: 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer (Elecsys 2000; Roche Diagnostics). Response was evaluated using evaluated criteria in solid tumors (RECIST) criteria. Results: 10 patients had partia None of the patients had complete response. 21/29 (72%) patients had an elevated baseline value of CYFRA 21-1. 62% paients (18/29 ) had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was ir- may of either baseline value was normal or not. The average reduction was measured significant (P = 0.002; 95% CI, from 0.8369 to 3.49464; t test). 8 out of 10 (80%) patients with partial response had a reduction in their 2nd reading of. CYFRA (P = 0.019; 95% CI, from 0.81965 to 7.20035; We also observed that 6/9 (66%) patients whose disease remains stable also had a decrease in their subsequent reading (P = 0.0106; 95% CI, from -0.44942 to 3.82720; t test), though it was not significant Although 5 out of 9 (55%) patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statist ic14 out of 19 (73%) who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21- 1 and was significant statistically (P = 0.004; 95% CI, from 0.74792 to 3.50208; t test). We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease (P = 0.001), which was statistically significant. Conclusion: We can conclude that monitoring of serum marker CYFRA 21-1, early during first-line chemotherapy may be useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC.