Anlotinib or platinum-pemetrexed as second-line therapy in EGFR T790M-negative lung cancer.

BACKGROUND: Clinical management of T790M-negative patients after first-line epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment failure is controversial. Anlotinib is a novel multi-target TKI for tumor angiogenesis and tumor cell proliferation, and it has been approved as a thirdline or beyond treatment for advanced non-small cell lung cancer (NSCLC). The impact of anlotinib as a second-line therapy compared with platinum-pemetrexed chemotherapy in T790M-negative patients after first-line EGFR-TKIs failed remains unclear. METHODS: In this retrospective cohort study, we reviewed 20 patients who were given anlotinib and 42 patients who received platinum-pemetrexed chemotherapy as a control after first-line EGFR-TKIs therapy progression. All the patients were confirmed to be T790M-negative using the cobas EGFR Mutation Test. The primary end point included progression-free survival (PFS) time, objective response rate (ORR) and disease control rate. RESULTS: The duration of PFS was significantly longer in the platinum-pemetrexed group than in the anlotinib group (median, 4.5 vs. 3.0 months; HR, 1.972; 95% CI, 1.078 to 3.607; P=0.021). The response rate was significantly better in the platinum-pemetrexed group (30.9%) than that in the anlotinib group (15%), and disease control rate (DCR) of both groups was 70% and 83%, respectively. All the adverse events in anlotinib group appeared to be manageable. CONCLUSIONS: Anlotinib was less effective than platinum-pemetrexed chemotherapy in T790M-negative NSCLC patients after disease progression with first-line EGFR-TKIs therapy failure.

RAD18 polymorphisms are associated with platinum-based chemotherapy toxicity in Chinese patients with non-small cell lung cancer.

AIM: Although targeted therapy is very efficient for lung cancer, traditional platinum-based chemotherapies are still the principal strategy in the absence of positive biomarkers. The aim of the present study is to evaluate the contribution of RAD18 polymorphisms to platinum-chemotherapy response and its potential side effects in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: A total of 1021 Chinese patients with histological diagnosis of advanced NSCLC were enrolled. Treatment responses were classified into 4 categories (complete response, partial response, stable disease and progressive disease). Gastrointestinal and hematological toxicity incidences were assessed twice a week during the first-line treatment. Ten RAD18 SNPs were genotyped. A logistic regression model was utilized to analyze the associations between RAD18 SNPs and treatment response or toxicity. RESULTS: Among the 10 SNPs tested, none was significantly correlated with the treatment response in a combined cohort. For gastrointestinal toxicity incidences, rs586014 was significantly associated with an increased risk of grade 3 or 4 gastrointestinal toxicity in non-smokers and in the combined cohort; rs654448 and rs618784 were significantly associated with gastrointestinal toxicity in non-smokers; rs6763823 was significantly associated with gastrointestinal toxicity in smokers. For hematological toxicity incidences, rs586014, rs654448 and rs618784 were significantly associated with hematologic toxicity in non-smokers; rs6763823 and rs9880051 were significantly associated with leukocytopenia in smokers. CONCLUSION: RAD18 polymorphisms are correlated with the side effects of platinum-chemotherapy in Chinese patients with advanced NSCLC.

Can determination of circulating endothelial cells and serum caspase-cleaved CK18 predict for response and survival in patients with advanced non-small-cell lung cancer receiving endostatin and paclitaxel-carboplatin chemotherapy? a retrospective study.

INTRODUCTION: Early prediction of the efficacy of a combination of an antiangiogenic drug with cytotoxic chemotherapy is a significant challenge. In that regard, circulating endothelial cells (CECs) and cytokeratins (CKs) seem to reflect their roles in both tumor angiogenesis and tumor cell death. METHODS: Patients with advanced, previously untreated non-small-cell lung cancer were randomly assigned to an endostatin treatment group (paclitaxel + carboplatin + endostatin) and a control group (paclitaxel + carboplatin + placebo). A total of 122 patients were evaluated, of whom 107 had measurements of blood CECs, CK8, caspase-cleaved CK18 (ccCK18), and uncleaved CK18 (CK18) before and at weeks 3 and 6 of treatment, respectively. RESULTS: Higher baseline CECs in patients with a tumor response (partial remission + stable disease, p = 0.002 for the entire group; p = 0.000 for the treatment group) were observed. The number of CECs decreased significantly after endostatin treatment (p = 0.000), whereas CK levels increased. Increased levels of ccCK18 and CK18, but not CK8, reached significance (p = 0.001 and p = 0.048, respectively) when compared with the baseline. Tumor response showed a strong correlation with reduction of CECs (p = 0.000) and increase of ccCK18 (p = 0.040) after endostatin therapy. Cutoff values of changes of CECs and ccCK18 for prediction of survival were 0.58/µl and 19.6 ng/ml, respectively. Reduction of CECs and increase of ccCK18 significantly correlated with longer median survival (p = 0.013 and p = 0.016 for progression-free survival; p = 0.009 and p = 0.012 for overall survival, respectively). CONCLUSIONS: CECs and CKs could be biomarkers for selecting patients with non-small-cell lung cancer who will benefit from treatment with endostatin in combination with paclitaxel plus carboplatin.

A clinicopathological study of resected non-small cell lung cancers 2 cm or less in diameter: a prognostic assessment.

The detection and diagnosis of small-sized (2 cm or less) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT). Over 80% of 5-year survival rate has been reported in surgically treated peripheral lung cancer. There are systematic mediastinal and hilar lymph node involvement pleural invasion and intrapulmonary metastasis even with tumor diameter less than 2 cm. The appropriate surgical procedure for such kinds of lung cancer is lobectomy with mediastinal lymph node dissection. To evaluate the prognostic factors and establish the optimal surgical strategy, we analyzed the clinicopathologic features and survival benefit in different tumor size of peripheral small-sized NSCLC. Among the resected lung cancer cases between January 1999 and July 2001, 185 patients were retrospectively analyzed in surgical methods, lymph node involvement, CT scan findings and survival rates. Survival was analyzed by Kaplan-Meier method and log-rank test. Lymph node involvement was recognized in 26(14.05%) patients. There was no statistically significant difference in the incidence of lymph node involvement between tumors 1.6-2.0 cm (17.82%) in diameter than in those 1.0-1.5 cm (11.94%). There was no lymph node metastasis in tumors less than 1.0 cm in diameter. The 5-year survival rates with or without lymph node involvement were 89.98 and 46.15%, respectively, showing significant difference (P=0.000). The overall 5-year survival rate was 83.78%. The 5-year survival rate in tumors 1.6-2.0 cm, 1.0-1.5 cm and less than 1.0 cm in diameter was 80.20, 85.07 and 100%, respectively, and showing significant difference (P=0.035). The 5-year survival rate of 19 patients showing ground-glass opacity (GGO) on CT scan was 94.74% without any metastasis and recurrence after operation. There are systematic mediastinal and hilar lymph node involvement even with tumor diameter less than 2 cm. The results of the present study suggested that systematic lymph node dissection is necessary even for cases with tumor diameter less than 2 cm. However, if the tumor is within 1.0 cm in diameter with obvious GGO showing on chest CT scan, these are good candidates for partial resection without mediastinal lymph node dissection.