Efficacy of Gemcitabine and S-1 for Patients with Advanced Pancreatic Cancer / 中国医学科学院学报

Objective To explore the efficacy and toxicities of gemcitabine combined with S-1 in treating locally advanced and metastatic pancreatic ductal adenocarcinoma and prognostic factors. Methods We retrospectively analyzed the clinical data of patients with locally advanced and metastatic pancreatic cancer receiving gemcitabine and S-1 as first-line therapy in the Department of Medical Oncology,Peking Union Medical College Hospital from January 2014 to January 2017.Gemcitabine was administered at a dose of 1000 mg/mover 30 min-utes on days 1 and 8,and oral S-1 at a dose of 40-60 mg twice daily from days 1 to 14,repeated every 3 weeks.All patients received at least two cycles of chemotherapy. Results A total of 60 patients were included,13(22%) achieved partial remission,37(61%) had stable disease,and 10(17%) experienced progressive disease.The median progression-free survival was 7 months(95% CI=6-10 months) and the median overall survival was 12 months(95% CI=9-20 months).Both univariate and multivariate analyses of prognostic factors showed primary resection was significant in predicting shorter progression-free survival and lung metastasis was significant for shorter overall survival.The most common grade 3-4 toxicities were neutropenia(27%) and leukopenia(18%). Conclusion Gemcitabine combined with S-1 is an effective regimen with manageable toxicities in the treatment of advanced pancreatic cancer and can be used as first-line therapy.

Single Nucleotide Polymorphisms of Paclitaxel-induced Peripheral Sensory Neuropathy in Chinese Han Population / 中国医学科学院学报

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

Folfox4 regimen administered through combined hepatic arterial and systemic infusion for treatment of colorectal cancer with unresectable liver metastases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases.</p><p><b>METHODS</b>Twenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m(2) and L-folinic acid 200 mg/m(2), followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m(2), then continuous HAI of 5-FU 600 mg/m(2); 2nd day: infusion of L-folinic acid 200 mg/m(2) i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400 mg/m(2), then continuous infusion of 5-fluorouracil 600 mg/m(2) i.v. The patients received HAI during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.</p><p><b>RESULTS</b>A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P < 0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/thrombocytopenia.</p><p><b>CONCLUSIONS</b>The Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.</p>

Treatment and prognosis of 77 cases of small cell lung cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical treatment modality and prognosis of small cell lung cancer(SCLC).</p><p><b>METHOD</b>We retrospectively analyzed the clinical data of 77 SCLC patients who were admitted to our department after 2002.</p><p><b>RESULTS</b>The disease was limited in 43 patients and extensive in 34 patients. For patients with limited SCLC, the 1-year, 2-year, and 5-year survival rate was 80%, 56%, and 21%, respectively. Four patients who had undergone surgical resection were all alive. Among patients who underwent adjuvant chemotherapy followed by radiotherapy, salvage chemotherapy, and salvage chemotherapy followed by radiotherapy, the median of survival period was 51 months, 12 months, and 28 months, respectively. For patients with extensive SCLC, the 1-year and 2-year survival rate was 56% and 25%, respectively. The median of survival period was 14.3 months. Stage was an independent factor in multifactor COX regression. Monofactor COX regression showed that radiotherapy and resection were factors correlated with survival. Brain metastasis had no impact on survival.</p><p><b>CONCLUSIONS</b>Chemotherapy followed by radiotherapy is preferred for limited SCLC, while surgical resection remains questionable for early-stage patients. For extensive SCLC, multi-line chemotherapy may be helpful to improve the overall survival. Stage is an independent factor for predicting the prognosis.</p>

Solid malignancies complicated with pulmonary embolism: clinical analysis of 120 patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulmonary embolism, a potentially fatal event, occurs more frequently in cancer patients than in the general population. To offer an accurate diagnosis and effective treatment to such patients in China, we analyzed the incidence rate and clinical features of pulmonary embolism in patients with solid tumor hospitalized in the Peking Union Medical College (PUMC) Hospital.</p><p><b>METHODS</b>A retrospective analysis was made of the hospitalized patients with solid malignancies complicated with pulmonary embolism who had been admitted into the PUMC Hospital from January 2002 to December 2008.</p><p><b>RESULTS</b>The incidence of pulmonary embolism in hospitalized patients with solid malignancies was 0.27% (120/43 967). The median age at diagnosis was 57.5 years. The male to female ratio was 1.0:1.4 (49:71). Patients with non-small-cell lung cancer (NSCLC) constituted the largest proportion of the 120 patients (37.5%), followed by patients with breast (9.2%), ovarian (8.3%), pancreatic (6.7%), and liver cancer (6.7%). Eighty patients (66.7%) had stage IV cancer. Bone was the most common site of distant metastasis (46.3%). D-dimer level was elevated in 90.9% of the 66 tested patients. The incidence of bleeding due to anti-coagulation therapy was 3.6%. Thirty-six (30.0%) of the 120 patients had concurrent deep venous thrombosis in the lower extremities. Seventeen patients developed acute pulmonary embolism within 2 weeks after surgery, 3 of whom died suddenly. Four patients presented with deep venous thrombosis and 1 with pulmonary embolism prior to the identification of malignancy.</p><p><b>CONCLUSIONS</b>Patients with cancer of the lung, ovarian, breast, pancreas, and liver are more likely to be complicated with pulmonary embolism than those with other types of solid tumors. Patients with distant metastasis are at a higher risk of pulmonary embolism. Pulmonary embolism without concurrent deep venous thrombosis is more frequently observed than concurrence of both disorders in the clinical setting.</p>

Inhibitory effect of low molecular weight heparin on the secretion of vascular endothelial growth factor by tumor cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate whether low molecular weight heparin (LMWH) may suppress the expression and secretion of vascular endothelial growth factor (VEGF) from tumor cells in vitro and inhibit the VEGF-induced proliferation of human tumor vascular endothelial cells.</p><p><b>METHODS</b>Human lung cancer cell line A549, human liver cancer cell line HepG2, human colon carcinoma cell lines HCT116 and HCT8 were used in this study. The expression levels of VEGF and TNF-alpha (tumor necrosis factor-alpha) in the tumor cells with or without pretreatment of LMWH/heparin were measured by standard sandwich ELISA technique. The VEGF mRNA level of HepG2 cells cultured with or without LMWH/heparin was determined by RT-PCR and real time PCR. Human umbilical vein endothelial cells (HUVEC) were cultured in tissue culture medium (TCM) with or without LMWH/heparin for 3 days. Then non-radioactive cell proliferation assay (MTS) kit and cell cycle assay by flow cytometry were performed to measure the proliferation of HUVEC.</p><p><b>RESULTS</b>The VEGF levels in the control, LMWH, and heparin groups of the pulmonary adenocarcinoma cell line A549 were (1045.89 +/- 165.30) pg/ml, (782.45 +/- 67.17) pg/ml and (916.54 +/- 71.25) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups of the colon adenocarcinoma cell line HCT116 were (955.76 +/- 51.14) pg/ml, (822.89 +/- 142.39) pg/ml and (951.77 +/- 188.22) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups in the colon adenocarcinoma cell line HCT8 were (1290.62 +/- 41.23) pg/ml, (1063.34 +/- 63.82) pg/ml and (1257.14 +/- 11.40) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups in the liver cancer cell line HepG2 were (1083.00 +/- 134.35) pg/ml, (758.00 +/- 84.85) pg/ml and (874.00 +/- 22.62) pg/ml, respectively. The VEGF expression levels in the above mentioned cell lines cultured in TCM were significantly reduced in the LMWH-treated groups compared with that of the control group (P < 0.05). But the level of TNF-alpha in TCM-cultured cells was unaffected by LMWH. The VEGF mRNA was reduced in the LMWH-treated HepG2 cell line. Moreover, TCM exhibited stimulating effect on proliferation of HUVEC and the effect was significantly impaired by LMWH treatment. Flow cytometric analysis revealed that LMWH treatment arrested HUVECs at the G1 phase of cell cycle.</p><p><b>CONCLUSION</b>LMWH can suppress the expression and secretion of VEGF by tumor cell lines and therefore have a potential inhibiting effect on angiogenesis induced by VEGF.</p>

Efficacy and safety of combination of irinotecan and capecitabine in patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of irinotecan combined with xeloda (CAPIRI regimen) in patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin.</p><p><b>METHODS</b>Totally 38 patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin were enrolled. Patients received xeloda 1 000 mg/m2 orally twice daily on day 1 to 14 and intravenous irinotecan 100 mg/m2 on day 1 and 8 every 3 weeks.</p><p><b>RESULTS</b>The median age of 38 patients was 58.5 (27-77) years. CAPIRI regimen was used 11.0 (3.0-24.0) months after the diagnosis of metastatic colorectal cancer (CAPIRI regimen as second-line chemotherapy in 33 patients, third-line in 4 patients, and fourth-line in 1 patient). A total of 121 cycles of chemotherapy (median 3.0) were administered. Thirty-four patients were evaluable for response. The overall response rate and disease control rate were 5.9% and 61.8%, respectively. The median time to progression and overall survival were 4.5 months (95% CI, 3.4-5.6 months) and 11.0 months (95% CI, 10.2-11.8 months), respectively. All 38 patients were evaluable for safety. The most common adverse events were leukopenia (73.7%), neutropenia (65.8%), nausea and vomiting (60.5%), and diarrhea (28.9%). The occurrence rates of these grade 3-4 events were 10.5%, 13.2%, 10.5%, and 7.9%, respectively. All adverse events were tolerable.</p><p><b>CONCLUSION</b>CAPIRI regimen is effective and well-tolerated in Chinese patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin.</p>