p53-associated differential response to platinumgemcitabine and platinum-paclitaxel in advanced nonsmall cell lung cancer

Background: Platinum-paclitaxel and platinum-gemcitabine are commonly used first-line chemotherapies for advanced non-small-cell lung cancer (NSCLC). Currently, there is no established biomarker predicting the treatment outcomes of these two regimens. Previous studies have suggested that p53 expression might determine the response to platinum compounds and gemcitabine, but not paclitaxel. We hypothesized that p53 overexpression would predict a worse response to platinum-gemcitabine than to platinum-paclitaxel in patients with advanced NCSLC.

Objective: To investigate whether tumor p53 expression would be able to predict the treatment outcome of these two chemotherapy regimens in advanced NSCLC patients.

Methods: We identified patients with advanced NSCLC who had been treated with either platinum-gemcitabine or platinum-paclitaxel as first-line chemotherapy at King Chulalongkorn Memorial Hospital. We obtained the corresponding archived tissue samples and performed immunohistochemical staining to determine the p53 expression in tumor tissues. We then compared the response rates and time to progression (TTP) between two regimens and p53 expression statuses.

Results: Of the 76 advanced NSCLC patients, we identified 40 (52.6%) patients with p53 overexpression, in which we showed better treatment outcomes with platinum-paclitaxel than with platinum-gemcitabine: the response rates were 42.1% vs 14.3% (p = 0.053) and TTPs were 5.3 [95%CI, 4.3-6.3] months vs 3.3 [95%CI, 1.3-5.2] months (p = 0.067). In the platinum-gemcitabine group, the response rate and TTP were better in normal expression of p53 subgroup compared to p53-overexpression subgroup (response rate 47.4% vs 14.3%, p = 0.026 and TTP 5.0 [95%CI, 4.4-5.5] months vs 3.3 [95%CI, 1.3-5.2] months, p = 0.062). These differences were not found in the platinum-paclitaxel group.

Conclusion: Our findings suggest that p53 expression is a potential predictive marker for the response to platinum-gemcitabine in advanced NSCLC. Consequently, platinum-paclitaxel would be favored over platinumgemcitabine in patients with p53 overexpression.