Abstract
Pemetrexed (PEM) is effective in first-line treatment for patients with non-squamous non-small cell lung cancer (NSCLC). However there are currently no definitive determinants to certify which patients could benefit from PEM. To improve the efficacy of PEM combined with platinum as first-line therapy for advanced non-squamous NSCLC, we conducted this retrospective study to detect potential determinants of this regimen. We recruited 109 patients with advanced non-squamous NSCLC who received PEM with a platinum as first-line therapy from June 2006 to February 2013 in Jiangsu Cancer Hospital. Multiple variables (age, sex, smoking, degree of cell differentiation, hemoglobin, platinum drugs combined, positions of metastasis) were selected. Logistic regression analysis was used to analyse relationships between these variables and tumor response. In univariate analysis, we found that age and platinum significantly influenced the results of PEM therapy (P<0.05). In multivariable analysis, no factors were independently significant. Our analysis did not suggest that the age, sex, metastasis of liver or other organs, hemoglobin, smoking history and pathological differentiation are associated with the response of PEM. We should conduct further analyses with larger sample size to reconfirm this issue.
Highlights
According to WHO statistics, the incidence and fatality rate of lung cancer increase year by year
Our analysis did not suggest that the age, sex, metastasis of liver or other organs, hemoglobin, smoking history and pathological differentiation are associated with the response of PEM
The mechanism of action consists of the inhibition of three key enzymes in the folate metabolic pathway, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT) (Giovannetti et al, 2005)
Summary
According to WHO statistics, the incidence and fatality rate of lung cancer increase year by year. In China, more than 75% of patients with non-small cell lung cancer (NSCLC) present with locally advanced (stage IIIB) or metastatic (stage IV) disease at diagnosis (Zhou et al, 2011) For patients in this setting, platinum-based chemotherapy is recommended as first-line treatment according to current guideline (Pfister et al, 2003). The mechanism of action consists of the inhibition of three key enzymes in the folate metabolic pathway, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT) (Giovannetti et al, 2005) This mechanism leads to depletion of fully reduced folate, resulting in disruption of nucleotide synthesis for both pyrimidines and purines. We retrospectively reviewed the records, pathological reports, and imaging studies of eligible patients and compared the characteristics of responders with those of none-responders These groups of patients were analyzed for significance of sex, age, smoking history, pathological differentiation, platinum combined, hemoglobin and sites of metastasis. Design a model for the judgment of PEM response, we conduct this study to identify factors that could indentify patients who could mostly benefit from PEM therapy
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