Clinical and biologic factors associated with time to progression in patients treated by first-line palliative FOLFOX chemotherapy in metastatic colorectal cancer.

e14159 Background: Chemotherapy is the mainstay of treatment patients with metastatic colorectal cancer. The choice of first-line treatment is difficult, especially when cost-effectiveness is the primary constraint. Thus, the optimal use of the clinical and biological factors influencing prognosis would be beneficial. The aim of our study was to identify factors affecting the time to progression (TTP) after first-line FOLFOX chemotherapy in palliative setting. Methods: The study is a retrospective analysis of the series of consecutive patients from large cancer center in south of Poland. The analysis was carried out in the group of 180 patients (37.2% of women), treated between 2007-2010 by FOLFOX-4 regimen and followed-up with the median time of observation 16.3 month. Patients received chemotherapy with median time of 5.0 months, median 10 cycles. Progression was defined as PD by RECIST criteria, death due to disease or sympomatic deterioration. 94 paraffin blocks were available for KRAS testing and gene expression analysis by real-time PCR. Results: The median TTP (counted from beginning of chemotherapy) was 8.6 month, the median TTP from the end of treatment was 3.4 month. We tested the wide range of clinical variables associated with both disease and and patient status by multivariate Cox regression analysis. Two most potent independent negative predictors were identified: the presence of massive lymph node involvement as assessed in CT scan before palliative treatment (>10 nodes enlarged) – hazard ratio 2.82, p<0.001; and tumor grade in histopathological assessment (grade 3 vs. grade 1-2) – hazard ratio 2.76, p=0.003. KRAS status was not prognostic for the TTP; Ki67 gene expression measurement by quantitative RT-PCR did not predict better that the routine assessment of grade. Patients with either grade 3 or lymph node involvement showed significantly shorter TTP (median 5.7 months vs 9.7 months in patients with none of these factors). Conclusions: High tumor grade and the massive involvement of lymph nodes worsen prognosis and shorten time to progression in patients treated with first line palliative FOLFOX chemotherapy.