ABSTRACT
BACKGROUND: Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in approximately 30% to 40% of colorectal adenocarcinomas. Wild-type (WT) KRAS mutation status is predictive of tumor response with epidermal growth factor receptor-directed therapies, but the results from studies evaluating the prognostic value of KRAS status in localized disease have been contradictory. The prognostic value of KRAS in metastatic disease, specifically according to whether patients have synchronous or metachronous disease at presentation, is less understood. METHODS: One-hundred ten consecutive patients with metastatic colorectal adenocarcinoma underwent testing for KRAS exon 2 mutations by polymerase chain reaction amplification and direct nucleotide sequencing. The clinical characteristics, treatments, and outcomes of these patients were then analyzed retrospectively, stratified according to whether patients presented with synchronous or metachronous metastasis and according to KRAS mutation status (WT or mutated). RESULTS: For the entire cohort, the median overall survival from the date of diagnosis of metastatic disease was 34.3 months (95% confidence interval, 28.3-49.4 months) for patients with WT KRAS (n = 70). The median overall survival for patients with mutated KRAS (n = 40) was 40.3 months (95% confidence interval, 27.9-51.1 months; log-rank P = .91). Kaplan-Meier survival analysis indicated that 3-year overall survival and 5-year overall survival were not statistically different. Within the subgroups of patients with synchronous and metachronous metastatic disease, no significant differences were observed in median overall survival, 3-year overall survival, or 5-year overall survival between the WT KRAS and mutated KRAS groups. CONCLUSIONS: In this study, KRAS mutation status did not influence overall survival in either synchronous or metachronous metastatic colorectal adenocarcinoma and, as such, had no prognostic role in this disease setting.
Subject(s)
Adenocarcinoma/genetics , Colorectal Neoplasms/genetics , Liver Neoplasms/genetics , Mutation/genetics , Neoplasms, Multiple Primary/genetics , Neoplasms, Second Primary/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/mortality , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/mortality , Neoplasms, Second Primary/pathology , Prognosis , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Survival Rate , Tertiary Care Centers , Young AdultABSTRACT
OBJECTIVES: There is a paucity of data exploring treatment options for refractory pancreatic cancer. Oxaliplatin has interesting activity in second-line therapy. Fixed-dose-rate gemcitabine (GFDR, 10 mg/m(2)/min) has shown promising results in patients with advanced pancreatic cancer over standard-dose-rate (30 min) gemcitabine (GSDR). METHODS: We conducted a retrospective analysis of the experience of our cancer center with GFDR and oxaliplatin (GEMOX) in patients who failed GSDR. GEMOX consisted of gemcitabine 1,000 mg/m(2) over 100 min on day 1 and oxaliplatin 100 mg/m(2) over 2 h on day 2 every 2 weeks. Eligible patients were required to have measurable metastatic adenocarcinoma of the pancreas and to have failed prior GSDR. RESULTS: Seventeen patients (median age 62 years) who were treated at the Ohio State University with GEMOX following GSDR failure between November 2003 and January 2008 were included in this study. Twenty-four percent of all patients had a partial response, 29% had stable disease and 47% had progressive disease. The median progression-free survival was 2.6 months and the median overall survival was 6.4 months. There were no unexpected toxicities. CONCLUSION: GEMOX shows interesting activity and acceptable tolerability in patients with metastatic pancreatic cancer who failed prior GSDR. Our results are consistent with previously published results.
