Zhiyu Chen

Primary small intestinal malignant tumors: survival analysis of 48 postoperative patients.

Background Primary small intestinal malignant tumor is relatively uncommon compared to gastric and colorectal cancer. It is difficult to make an early diagnosis due to the atypical primary symptoms and lack of effective diagnostic methods. Goals To analyze the relationship between the prognoses, histologic type, and therapeutic strategy in postoperative patients with small intestinal tumor. Study The parameters that affect survival were evaluated using multivariate Cox analysis in 48 cases of small intestinal tumor (confirmed by operation and pathology) for the past 10 years. Results The overall survival (OS) of all 48 cases after surgery was 28 months. The 5-year postoperative survival rate for all of the 48 cases was 27.1%. The median OS for all the 20 stage II/III patients who received adjuvant chemotherapy was 28 months, whereas the median OS for the 15 patients who did not receive the therapy was 37 months (P=0.276). The median time to progression for 8 patients with adenocarcinoma who received 5-fluorouracil or platinum-based palliative chemotherapy was 7 months, whereas for the patients who did not receive the therapy it was 3 months (P=0.06). The result of multivariate analyses showed that only the clinical stage was significantly correlated with OS (P<0.001). Conclusions The prognosis for small intestinal malignancies is associated with clinical stage, and palliative chemotherapy with a 5-fluorouracil or platinum-based regimen offers a potential benefit to patients with adenocarcinoma. Postoperative adjuvant chemotherapy seems to hold no therapeutic or survival benefit for patients with primary small bowel malignancies.

Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study

Background Maintenance therapy proves to be effective in advanced lung and breast cancer after initial chemotherapy. The purpose of this phase II study was to evaluate the efficacy and safety of Uracil and Tegafur (UFT) maintenance in metastatic gastric cancer patients following the first-line fluorouracil-based chemotherapy. Methods Metastatic gastric cancer patients with stable disease or a better response after the completion of first-line chemotherapy were randomized to oral UFT (360mg/m2 × 2 weeks) every 3 weeks until disease progression/intolerable toxicity or to observation (OBS). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS) and safety. Results The trial was closed after the interim analysis of the 58 enrolled (120 planned) patients. Median PFS was not improved in the UFT group compared with the OBS group (3.2 months versus 3.6 months, P = 0.752), as well as the median OS (14.2 months for both, P = 0.983). However, subgroup analysis showed that low baseline hemoglobin (< 120 g/L) was associated with poorer PFS with maintenance therapy (P = 0.032), while the normal hemoglobin patients benefit from the UFT treatment (P = 0.008). Grade 3 to 4 toxicities in the UFT group were anemia (3.4%), thrombocytopenia (3.4%) and diarrhea (6.9%). Conclusions This trial did not show superiority of UFT maintenance in non-selected patients responding to fluorouracil-based first-line chemotherapy. The normal hemoglobin level at baseline is a predictive biomarker for favorable patient subsets from the maintenance treatment.

Phase I Dose‐Escalation Study of Ramucirumab in Chinese Patients with Advanced Solid Tumors

Abstract Lessons Learned. Ramucirumab was well tolerated in Chinese patients with advanced solid tumors, and adverse events were manageable in this study. Pharmacokinetics characteristics in Chinese patients were similar to those in other populations. Immunogenicity was not detected. No efficacy conclusion could be drawn, and further randomized studies are warranted. Background. This single‐arm, nonrandomized, open‐label, dose‐escalation, phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of ramucirumab in Chinese patients with advanced solid tumors that were resistant to standard therapy or no standard therapy was available. Methods. Dose escalation was a 3 + 3 design, with expansion in Cohorts 2 and 3 for PK. Ramucirumab was given intravenously at three different dosages: 6 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, and 8 mg/kg every 2 weeks. Safety analyses included all patients. PK, immunogenicity, and antitumor activity were also assessed. Results. Among 28 patients treated, 2 experienced dose‐limiting toxicity, possibly related to ramucirumab. No maximum tolerated dose was determined. All patients experienced at least one treatment‐emergent adverse event. Grade ≥3 adverse event was reported for 53.6% (n = 15) of patients. PK analyses indicated that ramucirumab had low clearance, small volume of distribution, and long half‐life in Chinese patients, as in other populations. Immunogenicity was not detected. No patient had complete/partial response, and 64.3% (n = 18) had stable disease with a median duration of 5.55 months (95% confidence interval: 3.38−7.13 months). Conclusion. Ramucirumab appeared to be well tolerated in Chinese patients with advanced solid tumors. PK characteristics in Chinese patients were similar to those in other populations.

Influence of SLCO1B1 in gastric cancer patients treated with EOF chemotherapy

Cytochrome-P450 enzymes, ATP-binding cassette transporters, and solute carriers mediate drug metabolism as metabolic enzymes and membrane transporters, respectively. The present study investigated whether single nucleotide polymorphisms (SNPs) in genes encoding these proteins were predictive or prognostic factors in patients with metastatic gastric cancer (MGC) undergoing chemotherapy. A retrospective study of 108 MGC patients who received epirubicin, oxaliplatin, and 5-fluorouracil (EOF) as first-line treatment was performed. A total of 13 SNPs were genotyped, including SLCO1B1 (rs4149056), SLC2A9 (rs16890979, rs6449213, rs734553), ABCG2 (rs2231142), CYP2C9 (rs1057910, rs1799853), CYP2C19 (rs72552267, rs28399504, rs56337013, rs41291556) and CYP1A2 (rs12720461, rs56107638). The associations between these genotypes and disease-control rate (DCR), progression-free survival (PFS) and overall survival (OS) were analyzed. Patients with SLCO1B1 rs4149056 TT genotype had a significantly shorter OS compared with those with a C allele (CC + CT; 312 vs. 565 days, P=0.039). Multivariate analysis revealed that the rs4149056 TT homozygous genotype was an independent prognostic factor for shorter OS (hazard ratio: 2.565, 95% confidence interval: 1.215–5.415, P=0.014). However, no significant associations between SLCO1B1 rs4149056 and PFS were observed, between the other 12 SNPs and PFS or OS, or between any of the 13 SNPs and DCR. In conclusion, SLCO1B1 rs4149056 TT may be an independent predictor of survival in patients with MCG treated with EOF chemotherapy.

Influence of hypoxia‑related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF

Tumor hypoxia is common in a number of solid tumor types including gastric cancer, and is associated with treatment resistance and poor prognosis. The present study aimed to investigate the function of hypoxia-associated genetic polymorphisms in predicting treatment response and survival in patients with metastatic gastric cancer (MGC) treated with EOF (oxaliplatin and 5-fluorouracil combined with epirubicin) as first-line chemotherapy. The present retrospective study enrolled 108 Chinese patients with MGC receiving EOF as first-line chemotherapy, and genotyped six single nucleotide polymorphisms (SNPs) in four hypoxia-associated genes [myoglobin (MB) rs7292 and rs7293, ATP Binding Cassette Subfamily G Member 2 rs2231142, MutL homolog 1 (MLH1) rs1800734 and rs9852810, and Poly(ADP-Ribose) Polymerase 1 rs1136410]. The results of the present study indicated that the CT/TT genotype of MB rs7292, as well as the GG genotype of MLH1 rs9852810, were independent favorable predictive factors of progression-free survival [PFS; MB rs7292: hazard ratio (HR)=0.135, 95% confidence interval (CI)=0.057-0.321, P<0.001; MLH1 rs9852810: HR=0.494, 95% CI=0.267-0.913, P=0.024). Using a prognostic index based on the favorable SNPs for PFS (MB rs7292 CT/TT genotype, and MLH1 rs9852810 GG genotype), patients were classified into a low-risk group (involving one or two of the two SNPs) and a high-risk group (involving neither of the two SNPs), with a PFS of 180.0 and 117.0 days, respectively (P=0.002). The results of the present study demonstrated that the CT/TT genotype of MB rs7292 and the GG genotype of MLH1 rs9852810 were independent favorable predictive factors of PFS in patients with MGC treated with EOF. Identification of those SNPs in blood samples may allow for the prediction of the short-term efficacy of first-line EOF treatment in patients with MGC.