Carmen Viada González

Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy.

Background: Over-expression of epidermal growth factor receptor in esophageal cancer is associated with poor prognosis. The present study was conducted to evaluate safety and preliminary efficacy of nimotuzumab, a humanized anti-EGFR antibody in combination with radiation and chemotherapy in advanced esophageal tumours. Patients and Methods: A Phase II clinical trial was conducted, where patients received cisplatin, 5-fluorouracil, and radiotherapy, either alone or combined with six weekly infusions of nimotuzumab at the dose of 200 mg. Safety was the primary endpoint. The antitumoral objective response rate was the secondary endpoint. Epidermal growth factor receptor expression, KRAS mutation status and anti-idiotypic response were also evaluated. Results: Sixty-three patients were included in the study. Thirty patients were entered into the control group, and thirty-three patients received the treatment with nimotuzumab. The antibody was very well tolerated. Objective response rate was 47.8 % (nimotuzumab group) and 15.4 % (control group). Disease control rate was 60.9 % (nimotuzumab group) and 26.9 % (control group). Response and disease control rate were higher in patients with EGFR overexpressing tumors. Conclusion: Nimotuzumab plus chemoradiotherapy was safe and provided statistically significant objective response. A Phase III in patients with similar characteristics will be launched.

Effect of blockade of the EGF system on wound healing in patients vaccinated with CIMAvax® EGF

Background The epidermal growth factor receptor (EGFR) signaling system is frequently unbalanced in human malignancies due to increased ligand production, receptor overexpression, receptor mutations, and/or cross-talk with other receptor systems. For this reason, the EGFR is an attractive target for anticancer therapy. The epidermal growth factor also plays an important role in regulating multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis. In the Center of Molecular Immunology, a cancer vaccine is produced (CIMAvax® EGF) that blocks the binding of EGF to its receptor. This blockade causes a significant inverse association between the anti-EGF antibody titers and EGF concentration. Around 1,500 patients with non-small cell lung cancer have been treated, showing that this vaccine is safe, immunogenic, increases survival and improves quality of life. Taking into account the therapeutic benefits of CIMAvax® EGF vaccination and the role of EGF-EGFR system in the wound healing process, we decided to conduct a retrospective research with the aim of determining the effect to the CIMAvax® EGF vaccine on the wound healing process in patients undergoing surgical treatment.BackgroundThe epidermal growth factor receptor (EGFR) signaling system is frequently unbalanced in human malignancies due to increased ligand production, receptor overexpression, receptor mutations, and/or cross-talk with other receptor systems. For this reason, the EGFR is an attractive target for anticancer therapy. The epidermal growth factor also plays an important role in regulating multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis. In the Center of Molecular Immunology, a cancer vaccine is produced (CIMAvax® EGF) that blocks the binding of EGF to its receptor. This blockade causes a significant inverse association between the anti-EGF antibody titers and EGF concentration. Around 1,500 patients with non-small cell lung cancer have been treated, showing that this vaccine is safe, immunogenic, increases survival and improves quality of life. Taking into account the therapeutic benefits of CIMAvax® EGF vaccination and the role of EGF-EGFR system in the wound healing process, we decided to conduct a retrospective research with the aim of determining the effect to the CIMAvax® EGF vaccine on the wound healing process in patients undergoing surgical treatment.MethodsMedical records of 452 vaccinated patients were reviewed and only six patients receiving surgical treatment were identified. Further information about these six patients was obtained from source documents, including medical records and operative reports using an observational list that included different variables. Post-surgical wound healing complications were identified using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTC) version 3.0.ResultsNone of the six patients operated on presented adverse events related to the wound healing, that is to say, no wound dehiscence, wound infection, delayed wound healing, fistula formation, abscess formation or hemorrhage/bleeding associated with surgery during treatment with CIMAvax® EGF occurred.ConclusionsThese results suggest that the use of CIMAvax® EGF does not produce a deleterious effect in the wound healing process.

Effectiveness of adaptive designs for phase II cancer trials.

BACKGROUND Evaluation of new therapies for cancer has suffered a paradigm shift in the last years. The use of innovative and more efficient designs is a priority for the scientific community; nevertheless, the use of this kind of design is not yet wide spread. PURPOSE In this paper will examine the effectiveness of adaptive designs compared with traditional designs in phase II clinical trials. METHODS We reviewed a group of abstracts records between 1980 and 2008 and extracted data regarding statistical design, year of publication, kind of evaluated product, localization, sample size and results of the trials. RESULTS Nine hundred and eighty-nine clinical trials were identified and from them 333 traditional designs and 19 adaptive designs were included in the review. Two hundred statistical papers were located and 16 were included in the review. The most frequent designs were Standard up and down designs, continual reassessment methods and its variation and designs with Bayesian approaches. More than 80% of the studies evaluated different schemes of chemotherapy. Adaptive designs evaluated only drugs and not any kind of treatment combination and the most often localizations evaluated in both designs were lung, haematology malignancies, and colon cancers. CONCLUSIONS Adaptive designs are more efficient from the statistical point of view but they are not yet widely used because of complex and computationally intensive methods needed, substantial effort for planning the trials and lack of regulatory guidance.

Mejoras en el acceso a la información de los ensayos clínicos

El Centro de Inmunologia Molecular ha venido desarrollando biomoleculas para el tratamiento del cancer. En la medida que se avanza en el desarrollo de estos productos, se avanza en las fases I, II, III y IV de los ensayos clinicos, lo que trae aparejado un incremento en el numero de pacientes a tratar y en el numero de hospitales involucrados. Se cuenta con diez productos diferentes, implicados en mas de 50 ensayos clinicos, nacionales y multinacionales, con un pronostico de inclusion de 2 500 pacientes nuevos por ano. En este proceso estan incluidos alrededor de 30 hospitales en 13 provincias del pais. Para mejorar el acceso a la informacion de ensayos clinicos por parte de los investigadores comprometidos, se creo un sitio Web formado por cuatro secciones fundamentales, relacionadas con los productos y sus indicaciones, buenas practicas clinicas, la entrada remota de datos y la gerencia de los ensayos clinicos. Todo lo anterior mejora fundamentalmente la calidad de la informacion brindada a los investigadores clinicos involucrados y redunda en una mayor organizacion de la compleja actividad de los ensayos clinicos en Cuba.