lncRNA MALAT1, HOTTIP and PVT1 as predictors for predicting the efficacy of GEM based chemotherapy in first-line treatment of pancreatic cancer patients.

This study evaluated the lnc-RNAs as biomarker to predict efficacy of gemcitabine (GEM) based chemotherapy as the first-line treatment for locally advanced or advanced pancreatic cancer patients. We selected 62 patients with GEM based chemotherapy and divided two groups according to the PFS. We found that the expression of MALAT1, HOTTIP, and PVT1 in serum had a significant difference among the two groups. Furthermore, we estimated the PFS and response rate based on the expression levels of MALAT1, HOTTIP and PVT1. The response rate of two groups showed a significant difference according to the expression levels of MALAT1, HOTTIP and PVT1. Based on the expression levels of MALAT1, HOTTIP and PVT1, the response rate of high expression of PVT1 and low expression of PVT1 was respectively 14.8% and 37.1% and 18.2% (high HOTTIP group) and 37.9% (low HOTTIP group), 10.7%(high MALAT1 group) and 41.1% (low MALAT1 group). The PFS of patients with high and low expression levels PVT1 was 2.6 months and 4.0 months (p<0.001), respectively. The PFS of patients with high and low expression levels of HOTTIP was 2.7 months and 4.1 months (p<0.001), respectively, and the PFS of patients with high and low expression levels of MALAT1 was 3.0 months and 3.7 months (P=0.026), respectively. The results suggest that MALAT1, HOTTIP and PVT1 as predictors to predict the efficacy of GEM based chemotherapy in first-line treatment of pancreatic cancer patients.

Pemetrexed plus dendritic cells as third-line therapy for metastatic esophageal squamous cell carcinoma.

This study was conducted to evaluate the toxicity and efficacy of pemetrexed plus dendritic cells (DCs) when administered as third-line treatment for metastatic esophageal squamous cell carcinoma (ESCC). All patients in the study group had previously failed first-line treatment with 5-fluorouracil and cisplatin-based regimens, as well as second-line treatment with taxane-based regimens. A total of 31 patients were treated with pemetrexed (500 mg/m(2)) plus DCs on day 1, every 3 weeks. DCs were given for one cycle of 21 days. Thirty patients were evaluated for their response. No patient had a complete response, three patients (10.0%) had a partial response, ten patients (33.3%) had stable disease, and 17 patients (56.7%) had progressive disease. The overall response rate was 10.0%. The median progression-free survival (PFS) time was 2.9 months (95% CI, 2.7-3.2), and the median overall survival (OS) time was 7.1 months (95% CI, 6.4-7.9). The median PFS and OS times among patients with high and low levels of miR-143 expression in their blood serum were significantly different: median PFS times =3.2 months (95% CI, 2.9-3.4) and 2.7 months (95% CI, 2.4-3.0), respectively (P=0.017), and median OS times =7.8 months (95% CI, 6.8-8.9) and 6.3 months (95% CI, 5.3-7.3), respectively (P=0.036). No patient experienced Grade 4 toxicity. Combined third-line treatment with pemetrexed and DCs was marginally effective and well tolerated in patients with advanced ESCC. Serum miR-143 levels are a potential biomarker for predicting the efficacy of pemetrexed plus DCs in the treatment of ESCC.

Gemcitabine Plus Vinorelbine as Second-Line Therapy in Patients With Metastatic Esophageal Cancer Previously Treated With Platinum-Based Chemotherapy.

We evaluated the efficacy and feasibility of the combination of gemcitabine plus vinorelbine in patients with platinum-based chemotherapy-refractory esophageal cancer. We enrolled 35 patients who received gemcitabine plus vinorelbine as second-line treatment after platinum-based chemotherapy failure between May 2009 and April 2012. Dosage: gemcitabine 1,000 mg/m(2) plus vinorelbine 25 mg/m(2); all drugs were administered on days 1 and 8 of a 21-day cycle, and this was continued until failure or unacceptable toxicity. A total of 125 cycles of treatment were administered, and all patients received at least two cycles of treatment (two to five cycles; median number of cycles: three). Thirty-two patients were evaluable for response. The response rate was 31.3%, and the disease control rate (partial response plus stable disease) was 62.5%. The progression-free survival (PFS) was 4.3 ± 0.2 months [95% confidence interval (CI), 4.0-4.6], and the median overall survival (OS) was 7.3 ± 0.3 months (95% CI, 6.7-7.8). In the subgroup analysis, median PFS was 4.0 ± 0.2 months (95% CI, 3.6-4.3) in patients with high expression of miRNA-214, while it was 4.6 ± 0.3 months (95% CI, 4.1-5.1) in patients with low expression of miRNA-214 (log rank = 0.023). Myelosuppression with neutropenia and thrombocytopenia was the most common side effect observed with this combination regimen, and higher than grade 3 neutropenia and thrombocytopenia were observed in 10 (31.3%) and 8 patients (25.0%), respectively. Grade 3 fatigue was the most common nonhematologic toxicity, which was observed in 2 (6.1%) patients. The combination of gemcitabine plus vinorelbine was well tolerated as second-line treatment for platinum-based chemotherapy-refractory esophageal cancer patients and appeared to provide enhanced clinical activity especially in patients with low expression of miRNA-214.

MicroRNA 25, microRNA 145, and microRNA 210 as biomarkers for predicting the efficacy of maintenance treatment with pemetrexed in lung adenocarcinoma patients who are negative for epidermal growth factor receptor mutations or anaplastic lymphoma kinase translocations.

This study was conducted to evaluate microRNAs (miRNAs) as biomarkers for use in predicting the efficacy of maintenance therapy with pemetrexed in patients with stage IIIb or IV lung adenocarcinoma and who had already received first-line treatment with pemetrexed plus platinum. Patients who were negative for epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) translocations were assigned to a pemetrexed group and an observation group. Patients in the pemetrexed group (n = 76) received maintenance treatment with pemetrexed (500 mg/m(2), once every 21 days) plus best supportive care. Patients in the observation group (n = 72) agreed to receive only best supportive care until disease progression. Blood samples were collected from all patients in both groups before treatment and were used to detect expression levels of various miRNAs in serum by the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method. The expression levels of miR-25, miR-145, and miR-210 were significantly different in the 2 groups of patients. Furthermore, the median progression-free survival (PFS) times for patients in the pemetrexed and observation groups were 4.5 and 2.9 months, respectively. The PFS times among patients in the pemetrexed group varied significantly and were related to patient expression levels of miR-25, miR-145, and miR-210, whereas patients in the observation group showed no differences in PFS time. Our data suggest miR-25, miR-145, and miR-210 as predictors for the efficacy of maintenance treatment with pemetrexed in lung adenocarcinoma patients who were negative for EGFR mutations or ALK translocations.

Cetuximab plus pemetrexed as second-line therapy for fluorouracil-based pre-treated metastatic esophageal squamous cell carcinoma.

PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of cetuximab and pemetrexed as the second-line treatment for advanced esophageal cancer patients, who had undergone treatment with the standard cisplatin and 5-FU regimens. METHODS: A total of 29 patients accepted this treatment. Cetuximab was administered at an initial dose of 400 mg/m(2) IV followed by weekly doses of 250 mg/m(2) IV, whereas pemetrexed 500 mg/m(2) was administered on day 1 every 3 weeks. RESULTS: Twelve patients (41.4 %) presented PR, ten (34.5 %) had SD, and seven (24.1 %) had PD. The response rate was 41.4 %. The median PFS was 4.5 months (95 % CI 4.1-4.9), and the median OS was 9.4 months (95 % CI 8.4-10.5). The expression levels of serum miR-335 were determined, and the subsequent analysis suggested that PFS was significantly different between the patients with higher level of serum miR-335 and those with low level of serum miR-335. The former had a PFS of 4.9 months (95 % CI 4.2-5.7) and the latter 4.1 months (95 % CI 3.7-4.5) (log rank = 0.025). None of the patients experienced grade 4 toxicity. Twenty-four patients presented rash. CONCLUSIONS: A combination of cetuximab plus pemetrexed was marginally effective and well tolerated in patients with advanced esophageal squamous cell carcinoma as the second-line treatment.

Pemetrexed plus rituximab as second-line treatment for primary central nervous system lymphoma.

The aim of the study was to determine the efficacy and toxicity of pemetrexed plus rituximab in patients with primary central nervous system lymphoma, who had undergone treatment with high-dose (HD) methotrexate-based regimens. Patients who had failed HD methotrexate-based regimens treatment had ECOG performance status ranging from 0 to 2. Twenty-seven patients received pemetrexed plus rituximab as second-line treatment. Rituximab 375 mg/m(2) was administered on day 0 and pemetrexed 500 mg/m(2) was administered on day 1 every 3 weeks. Six patients (22.2 %) experienced CR, 11 patients (40.7 %) had PR, eight patients (29.6 %) had SD, and two patients had PD. The response rate was 62.9 %. The median time to progression (PFS) was 6.9 months (95 % CI, 5.6-8.3), and the median overall survival was 11.2 months (95 % CI, 9.1-13.4). In the subgroup analysis, PFS had a significant difference among the low level of serum miR-21 and high level of serum miR-21. PFS was 9.0 (95 % CI, 6.3-11.6) and 5.7 months (95 % CI, 4.6-6.9, log rank = 0.015), respectively. None of the patient experienced grade 4 toxicity. A regimen of pemetrexed combined with rituximab is marginally effective and well tolerated in patients with PCNSL who had failed HD methotrexate-based regimens first-line treatment.

Pemetrexed plus dendritic cells as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer who had treatment with TKI.

The aim of this study was to determine the efficacy and toxicity of pemetrexed plus dendritic cells (DCs) in patients suffering from stage IIIB or IV lung adenocarcinoma, who had undergone maintenance treatment with gefitinib or erlotinib. Patients who had failed gefitinib or erlotinib maintenance treatment had ECOG performance statuses ranging from 0 to 2.27 patients received pemetrexed plus DCs as second-line treatment. Dosage: 500 mg/m(2) pemetrexed was administered on day 1 of a 21-day cycle. DCs were given for one cycle of 21 days. Three patients (11.1 %) experienced a partial response and 14 patients (51.9 %) showed stable disease. Ten patients (37.0 %) had progressive disease. The median time to progression-free survival (PFS) was 4.8 months [95 % confidence interval (CI) 4.4-5.2], and the median overall survival was 10.7 months (95 % CI 10.3-11.2). In the subgroup analysis, PFS had a significant difference between the low ratio of CD4/CD8 and normal ratio of CD4/CD8, with 4.5 months (95 % CI 4.2-4.9) and 5.0 months (95 % CI 4.5-5.7), (Log Rank = 0.039), respectively. No one patient experienced grade 4 toxicity. A regimen of pemetrexed combined with DCs is marginally effective and well tolerated in patients with stage IIIB or IV lung adenocarcinoma who had received gefitinib or erlotinib first-line treatment.

Efficacy of erlotinib plus dendritic cells and cytokine-induced killer cells in maintenance therapy of advanced non-small cell lung cancer.

The aim of this study was to evaluate the safety and effectiveness of erlotinib plus DC/CIK in maintenance therapy of advanced non-small cell lung cancer. After 4 cycles of the 2-drug regimen treatment with platinum, the 54 patients with non-small cell lung cancer in phase IIIb or IV reached stable or beyond stable stages. The patients were then randomly divided into 2 groups. One group was treated with erlotinib therapy (erlotinib group), and the other was treated with DC/CIK plus erlotinib (DC/CIK plus erlotinib group). The progression-free survival of the erlotinib group and the DC/CIK plus erlotinib group was 3.98 months (95% CI, 3.56-4.40) and 5.02 months (95% CI, 4.32-5.72) (P=0.002), respectively. The median overall survival of the erlotinib group and the DC/CIK plus erlotinib group was 9.9 months (95% CI, 9.1-10.6) and 10.5 months (95% CI, 9.6-11.4) (P=0.29), respectively. The levels of CD3, CD4, and CD8 were significantly different before and after the treatment in the DC/CIK plus erlotinib group, but not in the erlotinib group. There was no significant difference in toxicity between the 2 groups. In conclusion, there was no statistically significant difference in overall survival between DC/CIK plus erlotinib and erlotinib as maintenance therapy. DC/CIK plus erlotinib was well tolerated with a manageable safety profile.

S-1 plus CIK as second-line treatment for advanced pancreatic cancer.

This study aimed to evaluate the efficacy and tolerability of S-1 (Tegafur, Gimeracil, and Oteracil Potassium Capsules) plus CIK (Cytokine-induced killer cells) in patients with advanced pancreatic cancer who had previously received gemcitabine-based therapy. In this prospective study, fifty-eight patients were randomly divided into two groups. One group (CT group) was given S-1 alone, and the other group (immuno-CT group) was given S-1 plus CIK. S-1 was administered orally twice a day at 80 mg/m(2)/day on days 1-21 of a 28-day cycle till disease progression or unacceptable toxicity occurred. CIK was given for one cycle of 28 days. The disease control rate for S-1 and CIK was 40.0 and 53.6%, respectively (p = 0.621). The serum CA19-9 level decreased for more than 25% was significantly different (33.3 and 60.7 % in CT group and immuno-CT group, respectively, p = 0.037). The median time to progression was 2.5 (95% CI 2.3-2.8) and 2.9 (95% CI 2.6-3.2) months (p = 0.037) for CT group and immuno-CT group, respectively. The median overall survival was 6.1 (95% CI 5.7-6.5) and 6.6 (95% CI 6.1-7.1) months (p = 0.09) for CT group and immuno-CT group, respectively. The difference in hematological toxicity, including leukocytopenia, anemia, and neutropenia, was insignificant between the two groups. In contrast, the differences in non-hematological toxicity, fatigue, and non-infective fever were significantly different between the two groups (p < 0.05). The S-1 plus CIK regimen was well tolerated in a second-line setting in patients with gemcitabine-refractory and advanced pancreatic cancer.

[Effect of second-line treatment with capecitabine and thalidomide in patients with advanced pancreatic cancer].

OBJECTIVE: This study investigates the efficacy and tolerability of capecitabine plus thalidomide in patients with advanced pancreatic cancer who previously underwent gemcitabine-based therapy. METHODS: Sixty-one patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen were enrolled. The patients were randomly divided into two groups. One group (31 patients) was treated with capecitabine alone, and another group was treated with capecitabine plus thalidomide. Capecitabine was administered orally twice a day at a dose of 1, 250 mg/m(2) for 14-day followed by 7-day rest and oral thalidomide 100 mg was given daily without interruption until disease progression or occurrence of unacceptable toxicity. RESULTS: The PFS was 2.8 months (95%CI 2.4 - 3.2) vs. 3.1 months (95%CI 2.6-3.6, P < 0.05) and the OS was 6.1 months (95%CI 5.3 - 6.9) vs. 6.3 months (95%CI 5.2 - 7.4, P = 0.426). In the capecitabine alone group, one patient experienced a partial response (PR), 10 patients showed stable disease (SD) and 20 patients had progressive disease (PD). The another group, two patients experienced a partial response (PR), 11 patients SD, and 17 patients PD. The disease control rates were 35.5% and 43.3%, respectively. The major adverse reaction in the two groups was grade 3 diarrhea. CONCLUSION: Capecitabine plus thalidomide regimen is marginally effective and well tolerated in the second-line setting in patients with gemcitabine-refractory advanced pancreatic cancer.

Treatment of stage IIIb/IV non-small cell lung cancer with Pemetrexed plus Oxaliplatin after failure of Erlotinib as second-line treatment.

To determine the efficacy and toxicity of Pemetrexed plus Oxaliplatin in patients suffering from stage IIIb or IV lung adenocarcinoma and being treated with Erlotinib as second-line treatment, a total of 45 patients were randomly divided into two groups. One group was treated with 500 mg/m(2) Pemetrexed plus 100 mg/m(2) Oxaliplatin, and the other was treated with 500 mg/m(2) Pemetrexed plus 75 mg/m(2) Cisplatin. All drugs were administered on day one of a 21-day cycle. In the Oxaliplatin group, 3 patients (13.6 %) experienced partial response (PR), 9 patients (41.0 %) showed stable disease (SD), and 10 patients (45.5 %) had progressive disease (PD). In the Cisplatin group, 2 patients (8.7 %) experienced PR, 7 patients (30.4 %) showed SD, and 14 patients (60.9 %) had PD. The PFS of the Oxaliplatin group and the Cisplatin group was 4.45 months (95 % CI 4.10-4.80) and 3.96 months (95 % CI 3.68-4.24) (P = 0.03), respectively. The median overall survival (OS) was 10.8 months (95 % CI 10.2-11.5) and 10.7 months (95 % CI 10.2-11.3) (P = 0.72), respectively. There was no statistically significant difference in the occurrence rate of grades 3 and 4 myelotoxicity between the two groups. However, there was a significant difference in the occurrence rate of grades 3 and 4 gastrointestinal reactions and peripheral neurotoxicity between the two groups (P < 0.05). A regime combining Pemetrexed and Oxaliplatin was marginally effective and well tolerated in patients with stage IIIb or IV lung adenocarcinoma who have received Erlotinib as second-line treatment.

Phase II trial of capecitabine combined with thalidomide in second-line treatment of advanced pancreatic cancer.

BACKGROUND: To evaluate the efficacy and tolerability of capecitabine combined with thalidomide in patients with advanced pancreatic cancer (APC) who have previously received gemcitabine-based therapy. METHODS: A total of 31 patients were recruited prospectively in Shandong Tumor Hospital from May 2007 to April 2009. Capecitabine was offered to patients twice a day at a dose of 1250 mg/m(2) for 14-day then followed by 7-day rest. Thalidomide was administered 100 mg/day without interruption until disease progression or occurrence of unacceptable toxicity. RESULTS: Two patients presented partial response (PR), 11 patients showed stable disease (SD) and eighteen patients presented progressive disease (PD). The median progression-free survival (PFS) was 2.7 months (95% confidence interval (CI), 2.4-3.3) and the median overall survival (OS) was 6.1 months (95% CI, 5.3-6.9). In the subgroup analysis, PFS had a significant difference between the serum CA19-9 level decreasing >25% and decreasing <25%, with 3.0 months (95% CI, 2.5-3.6) and 2.5 months (95% CI, 1.8-3.2), (Log Rank = 0.02), respectively. Hematological toxicity included leukocytopenia, anemia and neutropenia. Non-hematological toxicities included diarrhea, skin rash, nausea/vomiting, hand-foot syndrome, fatigue, dizziness, drowsiness and constipation. CONCLUSION: Capecitabine combined with thalidomide is a well-tolerated second-line regimen, in patients with APC refractory to gemcitabine.

Effect of maintenance therapy with dendritic cells: cytokine-induced killer cells in patients with advanced non-small cell lung cancer.

AIMS AND BACKGROUND: The incidence and development of cancer are closely related to dysfunction of immune function. The immune system cannot identify and remove malignant and mutant cells, which cause tumor cells to escape from surveillance and clearance of the immune system. Immunobiological cancer therapy plays an important role in strengthening body immunological surveillance function and killing remaining tumor cells in the body. We investigated the role of DC/CIK (dendritic cell/cytokine-induced killer cells) immunobiological cancer therapy in maintenance therapy of advanced non-small cell lung cancer. METHODS: When 60 cases of non-small cell lung cancer patients in stage IIIb and IV reached stable disease after treatment with 4 cycles of a two-drug regimen with platinum, they were randomly divided into two groups. One group was treated with DC/CIK immunobiological cancer therapy, and the other was taken as a control group. Finally, cancer progression time and toxicity reaction of the two groups were evaluated. RESULTS: DC/CIK treatment prolongs progression-free survival (3.20 months [95% CI, 2.94-3.50] vs 2.56 months [95% CI, 2.39-2.73]; P <0.05). In the treatment group, the proportion of NK cells, T-cell subgroups CD3+, CD4+ and CD8+ had a significant change before and after treatment. Liver and kidney function and blood tests of the treatment group were within the normal range before and after treatment. In the treatment group, 1 case suffered from chest distress, 3 cases suffered from acratia, and 4 cases suffered from pyrexia. CONCLUSIONS: DC/CIK treatment had potential benefit for patients with advanced non-small cell lung cancer compared with the control group and had no obvious side effects. DC/CIK treatment is a safe and effective method for maintenance therapy of advanced non-small cell lung cancer.