Prognostic Factors in Patients with Unresectable Pancreatic Cancer Treated with Gemcitabine: A Retrospective Analysis

Abstract

Gemcitabine therapy has been the standard first-line treatment for patients with unresectable local cancer. However 1-year survival rates of less than 20％ have been reported. Therefore, these results are unsatisfactory and also the prognostic factors are still not sufficiently discussed. We retrospectively analyzed the medical records of 88 patients who received gemcitabine mono-therapy for unresectable pancreatic cancer. The patient characteristics and treatment factors that may be associated with the survival as a patient's prognosis were investigated. The prognostic factors for survival were examined by univariate and multivariate analyses using the log-rank test and Cox proportional hazard analysis, respectively. Multivariate analysis identified gemcitabine total dose (≤ 9075 mg; hazard ratio HR, 3.10; P = 0.001), absence of second-line therapy (HR, 6.30; P < 0.001), stage IV-b (HR, 4.97; P = 0.005), neutrophil counts (> 3979.5 /μL; HR, 3.43; P = 0.003), lymphocyte counts (≤ 1155.5 /μL; HR, 2.94; P = 0.010), and carcinoembryonic antigen (CEA) levels (> 5.95 ng/mL; HR, 2.57; P = 0.034) as prognostic factors. We conducted additional data analysis including treatment regimens, because second-line chemotherapy is one of the prognostic factors. As indicated by the multivariate analysis, S-1 and gemcitabine combination therapy, S-1 and cisplatin combination therapy, and concurrent gemcitabineradiation therapy were not statistically significant when S-1 mono-therapy was the reference arm. In other words, S-1 mono-therapy is equivalent in efficacy when compared to other combination therapy. These prognostic factors could help to select treatment for patients in clinical practice, and these risk-adapted treatment strategies should be further investigated in a prospective study.

Neutropenia as a prognostic factor and safety of second-line therapy with S-1 for advanced or recurrent pancreatic cancer

“…Fridlender et al (17) reported that neutrophils are involved in vascularisation and are associated with cancer metastasis and angiogenesis. Hatori et al (4) reported that the number of neutrophils present prior to the first GEM treatment is a prognostic factor. Additionally, it has been reported that GEM, gemcitabine; S-1, tegafur, gimeracil, and oteracil potassium; BSA, body surface area; CrCl, creatinine clearance; RDI, relative dose intensity; GEM→S-1, group, patients who received GEM as first-line therapy and S-1 as second-line therapy; GEM group, patients who received GEM as first-line therapy and did receive second-line therapy.…”

“…It has been reported that second-line treatment with S-1 monotherapy is associated with a better prognosis in APC patients (4,(12)(13)(14). Similarly, this study has demonstrated that it is important to use GEM and S-1 for the treatment of APC.…”

“…Moreover, neutrophil count (4,5) and the ratio of neutrophils to lymphocytes (6,7) have been reported to be prognostic factors for APC patients. In addition, it has been reported that neutropenia is a prognostic factor in gastric (8) and colon cancers (9), as well as haematopoietic tumours (10).…”