Efficacy and safety of second-line camrelizumab combined with apatinib and chemotherapy in patients with advanced lung adenocarcinoma: A prospective, open-label, multicentric study.

OBJECTIVES: Camrelizumab (a programmed cell death protein 1 inhibitor) and apatinib (an angiogenesis inhibitor) are considered as potential treatments for advanced lung adenocarcinoma (LUAD). This study aimed to evaluate the efficacy and safety of second-line camrelizumab combined with apatinib and chemotherapy (albumin-bound paclitaxel, docetaxel, or pemetrexed) in patients with advanced LUAD. METHODS: Twenty-nine patients with advanced LUAD underwent second-line camrelizumab combined with apatinib and chemotherapy were enrolled in this prospective, open-label, multicentric study. Follow-up with a median duration of 18.0 months was conducted. RESULTS: There were 0 (0.0 %), 11 (37.9 %), 14 (48.4 %), and 3 (10.3 %) patients achieving complete response, partial response, stable disease, and progressive disease, respectively. Meanwhile, treatment response was not evaluated in 1 (3.4 %) patient. The objective response and disease control rates were 37.9 % and 86.3 %, respectively. In terms of survival, the median (95 % confidence interval) progression-free survival (PFS) was 11.1 (5.2-17.0) months, with 1-year and 2-year PFS rates of 40.4 % and 20.5 %, respectively. The median overall survival (OS) was not reached; the 1-year and 2-year OS rates were 72.0 % and 64.8 %, respectively. Current treatment cycles ≥ 8 were associated with better PFS and OS (both P < 0.001). In addition, 21 (72.4 %) patients experienced at least one treatment-emergent adverse event (TEAE), which was mostly of grade I and II. The most commonly occurring TEAE was leukopenia (17.2 %), liver dysfunction (17.2 %), hypothyroidism (13.8 %), hand-foot syndrome (13.8 %), and thrombocytopenia (13.8 %). CONCLUSION: Second-line camrelizumab combined apatinib and chemotherapy might serve as a potential treatment with acceptable safety in patients with advanced LUAD.

A phase II study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma.

AIM: To evaluate the efficacy and safety of paclitaxel-nedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma (ESCC). METHODS: A two-center, open-label, single-arm phase II study was designed. Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Patients received 175 mg/m² of paclitaxel over a 3 h infusion on 1 d, followed by nedaplatin 80 mg/m² in a 1 h infusion on 2 d every 3 wk until the documented disease progression, unacceptable toxicity or patient's refusal. RESULTS: Of the 36 patients assessable for efficacy, there were 2 patients (5.1%) with complete response and 16 patients (41.0%) with partial response, giving an overall response rate of 46.1%. The median progression-free survival and median overall survival for all patients were 7.1 mo (95%CI: 4.6-9.7) and 12.4 mo (95%CI: 9.5-15.3), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (15.4%), nausea (10.3%), anemia (7.7%), thrombocytopenia (5.1%), vomiting (5.1%) and neutropenia fever (2.6%). CONCLUSION: The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.

Correlation between the CD4+CD25high regulatory T cells and the outcome of chemotherapy in advanced esophageal carcinoma.

BACKGROUND/AIMS: In patients with esophageal carcinoma, local immune suppression and the expression of soluble immunosuppressive factors have been observed. We aimed to investigate the correlation between the level of CD4+CD25high regulatory T (Treg) cell and the outcome of chemotherapy in advanced esophageal carcinoma. METHODOLOGY: Forty-eight cases of advanced esophageal carcinoma patients were enrolled from June 2006 to December 2008. CD3+CD8+ T cell, CD3+CD4 T cell, CD4+CD25+ Treg cell and NK cell were determined before and after chemotherapy. After two cycles of chemotherapy, its effect was evaluated and the survival time was followed-up. RESULTS: Significant downregulation of CD4+CD25high Treg cell was noted in the advanced esophageal carcinoma patients after chemotherapy (p<0.05). However, there were no obvious differences in the CD3+CD8+ T cell, CD3+CD4+ T cell and NK cell before and after chemotherapy (p>0.05). Log-rank test showed age and the decrease of CD4+CD25high Treg cell after chemotherapy correlated with the median survival time (p<0.05). The COX multivariate analysis also suggested that the decrease of CD4+CD25high Treg cell after chemotherapy was an independent prognostic factor (p<0.05). CONCLUSIONS: Our results suggest that the downregulation of CD4+CD25high Treg cell after chemotherapy may be a predictor for the outcome of chemotherapy in advanced esophageal carcinoma patients.

Association of TNF-α-308 and -238 polymorphisms with risk of cervical cancer: a meta-analysis.

Published data on the associations between tumor necrosis factor-alpha (TNF-α) promoter -308G>A and -238G>A polymorphisms and cervical cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Data were collected from MEDLINE and PubMed databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a fixed/random effect model. 13 separate studies including 3294 cases and 3468 controls were involved in the meta-analysis. We found no association between TNF-α-308G>A polymorphism and cervical cancer in overall population. In subgroup analysis, significantly elevated risks were found in Caucasian population (A vs. G: OR=1.43, 95% CI=1.00- 2.03; AA vs. GG: OR=2.09, 95% CI=1.34-3.25; Recessive model: OR=2.09, 95% CI=1.35-3.25) and African population (GA vs. GG: OR=1.53, 95% CI=1.02-2.30). An association of TNF-α-238G>A polymorphism with cervical cancer was found (A vs. G: OR=0.61, 95% CI=0.47-0.78; GA vs. GG: OR=0.59, 95% CI=0.45-0.77; Dominant model: OR=0.59, 95% CI=0.46-0.77). When stratified by ethnicity, similar association was observed in Caucasian population (A vs. G: OR=0.62, 95% CI=0.46-0.84; GA vs. GG: OR=0.59, 95% CI=0.43-0.82; Dominant model: OR=0.60, 95% CI=0.44-0.83). In summary, this meta-analysis suggests that TNF-α-238A allele significantly decreased the cervical cancer risk, and the TNF-α-308G>A polymorphism is associated with the susceptibility to cervical cancer in Caucasian and African population.