Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma.

INTRODUCTION: Nectins are a family of integral protein and immunoglobulin-like cell adhesion molecules involved in the formation of functioning adherence and tight junctions. Aberrant expression is associated with cancer progression, apoptosis and cell proliferation but little is known how these effects change in cell behavior. The objective of this study was to evaluate the serum levels of nectin-2 with regard to diagnostic, predictive and prognostic value in colorectal cancer (CRC) patients. MATERIALS AND METHODS: One-hundred and forty CRC patients were enrolled in this study. Serum nectin-2 levels were determined by enzyme-linked immunosorbent assay method. Age- and sex-matched 40 healthy controls were included in the analysis. RESULTS: Median age of patients was 60 years old, range 24-84 years. The localization of tumor in majority of the patients was colon (n = 81, 58 %). Non-metastatic (stage II and III) and metastatic patients' baseline serum nectin-2 levels were significantly higher than those in the healthy control group (p < 0.001; for two group). However, known clinical variables including response to CTx (chemotherapy) were not found to be correlated with serum nectin-2 concentrations (p > 0.05). While non-metastatic group patients with elevated serum nectin-2 levels showed significant adverse effect on PFS, metastatic group patients with elevated serum nectin-2 levels showed no significant adverse effect on PFS (p = 0.05 and p = 0.29, respectively). On the other hand, our study results did not show statistically significant serum nectin-2 concentrations regarding overall survival rates. CONCLUSION: Serum levels of nectin-2 may have diagnostic roles for CRC patients. Moreover, our study results show the prognostic role of nectin-2 in non-metastatic group patients.

Clinical significance of serum circulating insulin-like growth factor-1 (IGF-1) mRNA in hepatocellular carcinoma.

The principal aim of our study was to investigate the usefulness of serum protein and circulating mRNA of insulin-like growth factor-1 (IGF-1) as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). Fifty-four HCC patients and age- and sex-matched 20 healthy controls were enrolled into this study. Pretreatment serum IGF-1 and IGF-1 mRNA were determined by the solid-phase sandwich ELISA and quantitative RT-PCR method, respectively. The median age at diagnosis was 60 years, range 36-77 years; where majority of group were male (n = 48, 88.8%). All patients had cirrhotic history. Forty-six percent (n = 25) of patients had Child-Pugh score A, 30% (n = 16) had score B or C. All of the patients were treated with local therapies and none of them received sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p = 0.04), whereas no significant difference was observed for IGF-1 protein levels between the two group (p = 0.18). Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p = 0.03, 0.03, and 0.05, respectively). Poor performance status (p < 0.001), viral etiology of cirrhosis (p = 0.03), larger tumor size (p = 0.01), lower serum hemoglobin levels (p = 0.03), and not be treated for HCC (p = 0.001) related to worse survival. However, neither serum IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p = 0.53 and 0.42, respectively).

The role of UFT in advanced gastric cancer.

BACKGROUND: Advanced gastric cancer has a poor prognosis, with a relative 5-year survival rate of 7%-27%. Chemotherapy, which improves overall survival (OS) and quality of life, is the main treatment option. Although numerous regimens have been investigated, there is no standard treatment. Combination chemotherapy, however, is associated with a significant survival benefit compared with monotherapy and i.v. 5-fluorouracil (5-FU) is one of the most widely used agents. UFT (tegafur-uracil) has similar efficacy to continuous infusion 5-FU with improved tolerability and is more convenient for patients. DESIGN: The efficacy and safety of UFT in the treatment of advanced gastric cancer have been demonstrated in a number of phase II studies. RESULTS: UFT with leucovorin (folinic acid) monotherapy shows overall response rates (ORRs) of 16%-29% and median OS of 5.8 months. Combination of UFT with cisplatin, etoposide, or paclitaxel shows ORRs of 35%-51% and median OS of 8.3-10.1 months. UFT-based three-drug combinations show ORRs of 41%-57% and median OS of 8.6-15 months. UFT-based combinations have a good tolerability profile, particularly a low incidence of myelosuppression, mucositis, and hand-foot syndrome. CONCLUSION: UFT represents a logical replacement for 5-FU in chemotherapy regimens for the treatment of advanced gastric cancer.

XELOX followed by XELIRI or the reverse sequence in advanced colorectal cancer.

BACKGROUND: Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (mCRC). In this non-randomized pilot study, we investigated the efficacy and safety of sequentially administered XELOX and XELIRI regimens or the reverse sequence in patients with advanced colorectal cancer. PATIENTS AND METHODS: Entry criteria were histologically confirmed mCRC, ECOG performance status (PS) < or =2 and adequate bone marrow, renal and hepatic function. All patients consecutively received XELOX followed by XELIRI at disease progression or vice versa. RESULTS: In multivariate analysis, independent prognostic factors with worse overall survival were: lower PS (p = 0.0001), multiple metastatic sites (p = 0.016) and high tumor grade. Higher serum levels of alkaline phosphatase and worse ECOG PS were associated with a shorter progression-free survival. Grade 3/4 mucositis, nausea/vomiting, grade 3/4 alopecia and grade 3 diarrhea were more frequent with XELIRI, whereas major toxicity events with XELOX were grade 3 neutropenia, thrombocytopenia and grade 2/3 neurotoxicity. CONCLUSION: Capecitabine appears to be an acceptable alternative to continuous-infusion fluorouracil (FU)/leucovorin (LV) in combination therapy and offers an effective, but more convenient alternative to continuous infusion FU/LV in the first-line treatment of patients with mCRC.

Alpha-interferon does not increase the efficacy of 5-fluorouracil in advanced colorectal cancer.

Two meta-analyses were conducted to quantify the benefit of combining alpha-IFN to 5FU in advanced colorectal cancer in terms of tumour response and survival. Analyses were based on a total of 3254 individual patient data provided by principal investigators of each trial. The meta-analysis of 5FU +/- LV vs. 5FU +/- LV + alpha-IFN combined 12 trials and 1766 patients. The meta-analysis failed to show any statistically significant difference between the two treatment groups in terms of tumour response or survival. Overall tumour response rates were 25% for patients receiving no alpha-IFN vs. 24% for patients receiving alpha-IFN (relative risk, RR = 1.02), and median survivals were 11.4 months for patients receiving no alpha-IFN vs. 11.5 months for patients receiving alpha-IFN (hazard ratio, HR = 0.95). The meta-analysis of 5FU + LV vs. 5FU + alpha-IFN combined 7 trials, and 1488 patients. This meta-analysis showed an advantage for 5FU + LV over 5FU + alpha-IFN which was statistically significant in terms of tumour response (23% vs. 18%; RR = 1.26;P = 0.042), and of a borderline significance for overall survival (HR = 1.11;P = 0.066). Metastases confined to the liver and primary rectal tumours were independent favourable prognostic factors for tumour response, whereas good performance status, metastases confined to the liver or confined to the lung, and primary tumour in the rectum were independent favourable prognostic factors for survival. We conclude that alpha-IFN does not increase the efficacy of 5FU or of 5FU + LV, and that 5FU + alpha-IFN is significantly inferior to 5FU + LV, for patients with advanced colorectal cancer.

The roles of chemotherapy and surgery in gastric carcinoma and the influence of prognostic factors on survival.

In this study, we present the results of surgery and chemotherapy and the impact of various prognostic factors on survival in patients with gastric carcinoma with a follow-up of 6 years. All of the 328 cases were adenocarcinoma histologically and had a median age of 55 years. Median survival was 11 months, and the 5-year survival rate was 18%. Nonmetastatic cases were associated with improved survival as compared with the cases with metastatic disease (p<0.001). Patients with gastrectomy had improved survival (p<0.001). Subtotal gastrectomized patients had better survival rates in comparison to the total gastrectomized patients (p = 0.03). Addition of splenectomy to total gastrectomy and adjuvant chemotherapy did not influence survival rates (p>0.05). In metastatic patients, we determined beneficial effects of gastrectomy and chemotherapy on survival. The benefit was most predominant in chemoresponsive patients (p<0.001). Higher serum CA 19.9 levels in patients without metastases, higher serum lactate dehydrogenase and carcinoembryonic antigen levels in patients with metastases, and lower serum albumin levels in both stages were determined as significant predictors of poor survival. On multivariate analysis, only higher serum CA 19.9 level was the independent unfavorable prognostic factor of survival time in nonmetastatic patients (p = 0.008). In metastatic disease, older age (p = 0.03) and male gender (p = 0.05) were associated with poorer survival. In conclusion, gastric cancer is a great health problem, especially in developing countries, and we need more optimal approaches and treatment modalities for gastric cancer.