Nimotuzumab Concurrent with Gemcitabine as First-Line Treatment of Locally Advanced or Metastatic Pancreatic Adenocarcinoma.

Background: Nimotuzumab exerts its antitumor effect (mainly antiproliferative, proapoptotic, and antiangiogenic) by blocking the epidermal growth factor receptor overexpressing between 30 and 95% in pancreatic tumors cells. Methods: A prospective, nonrandomized, uncontrolled, open-label, and multicenter clinical trial was conducted to evaluate the safety and effectiveness of nimotuzumab combined with gemcitabine as first-line treatment in unresectable locally advanced or metastatic pancreatic tumors in a real-world condition. Adverse events, their intensity, severity, and causality were determined using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). Median overall survival, median progression-free survival, and 1- and 2-year survival rates were determined by using the Kaplan-Meier. Results: 69 patients were included. The proportion of related serious adverse events was 1.2%. The most frequent adverse events were nausea (10%), anemia (8%), and abdominal pain (8%). Objective response was achieved in 18.5% of the patients and disease control in 43.1%. Patients with locally advanced disease achieved a median overall survival of 16.36 months (95% CI; 14.35-18.38); 1- and 2-year survival rates of 72.2 and 29.2 months, respectively; a median progression-free survival of 9.6 months (95% CI; 4.91-14.20); and a 1-year progression-free survival rate of 39%. Patients with metastatic disease achieved a median survival of 6.23 months (95% CI; 4.32-8.13); 1- and 2-year survival rates of 18.1 and 3.0 months, respectively; a median progression-free survival of 7.6 months (95% CI; 6.08-9.90); and 1- and 2-year PFS rates of 20.5 and 5.1 months, respectively. Conclusions: Nimotuzumab combined with gemcitabine represents a safe and effective first-line treatment option for patients with advanced pancreatic adenocarcinoma in real-world conditions. Survival benefits were increased in those patients who received 8 or more doses of nimotuzumab. This trial is registered with RPCEC00000245 in the Cuban Registry of Clinical Trials, part of the World Health Organization's International Clinical Trials Registry Platform (ICTRP).

Validation of Instruments for Assessing Drug Safety Management During the Conduction of Clinical Trials.

BACKGROUND: The management of drug safety with the collection of reliable safety data during the conduction of clinical trials conduct is essential for the registry and marketing of products. The systematic evaluation of this process, based on objective measures, requires the application of quality instruments. This study was aimed to design and validate eight instruments through the components of quality (structure, process, and results), for characterizing and assessing the process of drug safety management, during the conduction of clinical trials. METHODS: The eight instruments were designed according to the international recommendations for Good Clinical Practice (GCP) and comprise a knowledge survey for professionals at the investigational sites, a satisfaction scale of internal and external clients and a satisfaction survey for patients with the treatment of the adverse events. The instruments also include a checklist to evaluate the safety management infrastructure (human, material and organizational resources) in the sponsoring center, a checklist to evaluate the same criterion at the investigational sites and three checklists that evaluate adherence to regulatory requirements of essential documents (investigator's brochure, protocol, and informed consent form). The content validity was evaluated by Delphi method and the reliability was determined by Cronbach α test. RESULTS: All the items were valued as very adequate after the second round of the expert panel. The instruments were deemed as appropriate and understandable in the pre-test performed. All responders agreed with the options given and the accessibility of the application. Only 10% of professionals at the research sites suggested that the knowledge survey was too long. Cronbach α values between .66 and .93 were obtained. CONCLUSION: The structure, process, and outcome framework allowed for the characterization of drug safety management during clinical trials, providing a useful approach for the promoter to systematically measure and evaluate the process. The eight instruments were deemed as reliable, feasible and easy to be used for examining drug safety management while carrying out clinical trials.

Overall Survival of Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Nimotuzumab in the Real World.

INTRODUCTION: Despite improvements in surgical techniques and treatments introduced into clinical practice, the overall survival of patients with esophageal squamous cell carcinoma remains low. Several epidermal growth factor receptor inhibitors are being evaluated in the context of clinical trials, but there is little evidence of effectiveness in real-world conditions. This study aimed at assessing the effectiveness of nimotuzumab combined with onco-specific treatment in Cuban real-life patients with locally advanced or metastatic esophageal squamous cell carcinoma. METHODS: A comparative and retrospective effectiveness study was performed. The 93 patients treated with nimotuzumab were matched, with use of propensity score matching, with patients who received a diagnosis of locally advanced or metastatic squamous cell carcinoma of the esophagus in three Cuban provinces reported between 2011 and 2015 to the National Cancer Registry. The Kaplan-Meier method was used to estimate event-time distributions. Log-rank statistics were used for comparisons of overall survival between groups. A two-component mixture model assuming a Weibull distribution was fitted to assess the effect of nimotuzumab on short-term and long-term survival populations. RESULTS: There was an increase in median overall survival in patients treated with nimotuzumab (11.9 months versus 6.5 months without treatment) and an increase in the 1-year survival rate (54.0% versus 21.9% without treatment). The 2-year survival rates were 21.1% for patients treated with nimotuzumab and 0% in the untreated cohort. There were statistically significant differences in survival between groups treated and not treated with nimotuzumab, both in the short-term survival population (6.0 months vs 4.0 months, p = 0.009) and in the long-term survival population (18.0 months vs 11.0 months, p = 0.001). CONCLUSIONS: Our study shows that nimotuzumab treatment concurrent with chemoradiotherapy increases the survival of real-world patients with locally advanced or metastatic esophageal squamous cell carcinoma. Further prospective studies are required to confirm the therapeutic effectiveness of nimotuzumab in esophageal cancer.