Search

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. Methods: Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. Results: A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. Conclusions: Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.

Background: The changes in the risk of disease failure over time in nasopharyngeal carcinoma (NPC) remains unknown. Methods: We analyzed 749 patients treated with intensity-modulated radiotherapy in a single center. The annual hazard rates of disease failure (recurrence or death from any cause) were estimated using the life-table method. Results: In total, 41 (5.5%), 22 (2.9%) and 129 (17.2%) patients developed local, regional and distant recurrences, respectively; 149 (19.9%) patients died. Of the 600 patients who were alive at the last follow-up, 496 (82.7%) had follow-up times longer than 6 years. The 6-year failure-free survival rate was 74.8%. Older age (> 50 years) and advanced stage (Ⅲ-ⅣB) were independent risk factors for disease failure in multivariate analysis. The hazard curve for failure risk in the whole cohort showed a sharp peak at 2 years, changed to a gradually decreasing plateau between years 3 and 5 and then declined sharply. Subgroup analyses revealed similar hazard curves in both sexes. However, the patterns of hazard curve significantly differed between high-risk (> 50 years or stage Ⅲ-ⅣB) and low-risk (≤ 50 years or stage Ⅰ-Ⅱ) patients. Interpretation: The failure hazard rate in NPC didn't decline in a linear manner, but displayed a sharp peak at 2 years. The patterns of hazard function significantly differed between patients with different age and stage. Further studies are warranted to confirm our results.

Background: The optimal treatment for early-stage nasopharyngeal carcinoma (NPC) remains controversial. Identification of prognostic factors for metastasis and tumor progression is urgently required to improve clinical decision-making for patients with American Joint Committee on Cancer (AJCC) 2009 stage II NPC from the endemic area. Methods: Consecutive newly-diagnosed patients (n=296) with non-disseminated, biopsy-proven stage II NPC were retrospectively reviewed; all patients received intensity-modulated radiotherapy and MRI follow-up. Plasma EBV DNA level, serum lactate dehydrogenase, serum albumin, serum globulin and leukocyte counts were measured before therapy. Survival rates were analyzed using the Kaplan-Meier method and log-rank test and multivariate Cox proportional hazards model. Results: Median follow-up was 50.2 months (range, 8-69.5 months). Multivariate analysis demonstrated a plasma Epstein-Barr virus (EBV) DNA level ≥ 4000 copies/mL, maximal axial diameter (MAD) of the cervical lymph nodes ≥ 30 mm and serum globulin level < 29.5 g/L were independent predictors of poor DMFS (P = 0.018; P = 0.019; P = 0.006, respectively). On the basis of these parameters, a prognostic model was developed as follows: 1) patients with no risk factors; 2) one risk factor; and 3) two or three risk factors. The 3-year distant metastasis-free survival rates for groups 1, 2 and 3 were 100%, 94.6% and 84.3%, respectively (P = 0.001). Conclusion: The prognostic model based on EBV DNA, serum globulin and nodal size may facilitate individualized treatment of patients with stage II NPC at high risk of distant metastasis.