Clinical efficacy of protein-bound polysaccharide K in patients with gastric cancer undergoing chemotherapy with an oral fluoropyrimidine (S-1)

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Abstract

Background

The aim of the present study was to evaluate the clinical significance of protein-bound polysaccharide K (PSK) in patients with primary gastric cancer who were being treated with an oral fluoropyrimidine (S-1).

Methods

Clinical reports of 190 gastric cancer patients treated with S-1 chemotherapy, with or without PSK, at Kochi Medical School between 2007 and 2012 were investigated retrospectively to analyze survival. The neutrophil:lymphocyte ratio (NLR) was also evaluated as indicator of the immunoenhancing effect of PSK.

Results

Overall survival was significantly longer in patients treated with S-1 + PSK than in those given S-1 alone (hazard ratio for death, 0.608; 95% confidence interval 0.375–0.985; P = 0.041). Furthermore, there was a tendency for changes in the NLR during chemotherapy to be lower in the S-1 + PSK group than in the S-1 group, but the difference did not reach statistical significance (P = 0.054). When patients were divided into groups based on preoperative NLR (i.e. <2.5 and ≥2.5), the mean (±SEM) NLR 1 month after the beginning of chemotherapy in the NLR ≥2.5 subgroup was significantly lower in patients treated with S-1 + PSK rather than S-1 alone (1.7 ± 0.7 vs. 3.3 ± 4.1, respectively; P = 0.043).

Conclusions

Immunochemotherapy using PSK improves the survival of patients with advanced gastric cancer. The NLR may be a useful biomarker for evaluating prognosis in these patients.

Introduction

Gastric cancer is the third most common cancer and the second most common cause of cancer-related deaths worldwide. Although, gastric cancer is the most common malignancy in Asia, South America, and Eastern Europe, its rates are declining in North America and in most northern and western European countries.1, 2 In addition to advances in surgical techniques, recent large-scale randomized controlled trials have demonstrated that S-1, an oral fluoropyrimidine, plays an important role in improving the prognosis of patients with advanced gastric cancer.3, 4 S-1 is an oral anticancer drug that combines the pro-fluorouracil drug tegafur, an inhibitor of dihydropyrimidine dehydrogenase, and potassium oxonate in a molar ratio of 1:0.4:1.

To achieve greater improvements following chemotherapy for gastric cancer, S-1 is being used in combination with various anticancer agents. Protein-bound polysaccharide K (PSK), an oral biological response modifier isolated from the cultured mushroom Coriolus versicolor (Family Polyporaceae), has been used as an immunochemotherapeutic agent for the treatment of various cancers.5, 6, 7 It is difficult to evaluate the response to PSK because its efficacy is determined on the basis of antitumor immunoenhancing effects. The neutrophil:lymphocyte ratio (NLR) has been documented not only as a simple index of the systemic inflammatory response, but also as a predictive indicator of prognosis in critically ill patients with malignancy.8, 9

The survival benefits of immunochemotherapy with PSK in addition to S-1 for patients with gastric cancers are not widely accepted. In the present study we analyzed the outcomes of patients with primary gastric cancer treated with a combination of PSK and S-1 compared with patients treated with S-1 alone, and used the NLR as marker of immune function in patients to determine its prognostic significance.

Section snippets

Patients

The present study was a retrospective review of 190 patients with gastric cancer who underwent S-1 chemotherapy between January 2007 and December 2012 at Kochi Medical School. These patients had been pathologically diagnosed with gastric adenocarcinoma following endoscopic biopsy or surgery. Patients who underwent surgery had either a total or distal gastrectomy with standard lymphadenectomy. Patients with a history of other cancer therapy or those who had been treated with other anticancer

Patient characteristics

Table 1 summarizes the clinical characteristics of all patients in the present study. The study cohort comprised 119 men and 71 women with a median age of 68 years (range 56–80 years). Within the patient group, there were 16 cases of Stage I, 39 cases of Stage II, 57 cases of Stage III, and 78 cases of Stage IIIB adenocarcinoma. The incidence of total gastrectomy was significantly higher in the S-1 + PSK group than in the group treated with S-1 alone (55.6% vs. 36.5%, respectively; P = 0.032).

Discussion

In the present study, the OS of patients with advanced gastric cancer was significantly higher for those treated with S-1 + PSK than S-1 alone. Until now, there has been no adequate-sized study reporting on the results of treatment with the combination of PSK and S-1, even though PSK has been used as a non-specific immunostimulant in the treatment of cancer patients in Japan for more than 30 years.12, 13, 14 Previous studies reported that the addition of PSK to chemotherapy with agents such as

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