Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG) in patients with mycosis fungoides: an open-label trial.

BACKGROUND: The synergistic combination of interferon (IFN) alpha-2b and IFN gamma results in more potent in vitro biological effects mediated by both IFNs. The aim of this investigation was to evaluate by first time the pharmacokinetics and pharmacodynamics of this combination in patients with mycosis fungoides. METHODS: An exploratory, prospective, open-label clinical trial was conducted. Twelve patients, both genders, 18 to 75 years-old, with mycosis fungoides at stages IB to III, were eligible for the study. All of them received intramuscularly a single high dose (23 × 10(6) IU) of a novel synergistic IFN mixture (HeberPAG) for pharmacokinetic and pharmacodynamic studies. Serum IFN alpha-2b and IFN gamma concentrations were measured during 96 hours by commercial enzyme immunoassays (EIA) specific for each IFN. Other blood IFN-inducible markers and laboratory variables were used as pharmacodynamics and safety criteria. RESULTS: The pharmacokinetic evaluation by EIA yielded a similar pattern for both IFNs that are also in agreement with the well-known described profiles for these molecules when these are administered separately. The average values for main parameters were: Cmax: 263 and 9.3 pg/mL; Tmax: 9.5 and 6.9 h; AUC: 4483 and 87.5 pg.h/mL, half-life (t(1/2)): 4.9 and 13.4 h; mean residence time (MRT): 13.9 and 13.5 h, for serum IFN alpha-2b and IFN gamma, respectively. The pharmacodynamic variables were strongly stimulated by simultaneous administration of both IFNs: serum neopterin and beta-2 microglobulin levels (ß2M), and stimulation of 2'-5' oligoadenylate synthetase (OAS1) mRNA expression. The most encouraging data was the high increment of serum neopterin, 8.0 ng/mL at 48 h, not been described before for any unmodified or pegylated IFN. Additionally, ß2M concentration doubled the pre-dose value at 24-48 hours. For both variables the values remained clearly upper baseline levels at 96 hours. CONCLUSIONS: HeberPAG possesses improved pharmacodynamic properties that may be very useful in the oncologic setting. Efficacy trials can be carried out to confirm these findings. TRIAL REGISTRATION: Registro Público Cubano de Ensayos Clínicos RPCEC00000130.

Valor del método dermatoscópico ®Lista Recapitulativa de los Tres Puntos de Soyer¼ en el diagnóstico de las lesiones cutáneas pigmentadas en pacientes del Hospital Hermanos Ameijeiras, La Habana-Cuba, 2008 / Value of the Soyer´s Three Point Checklist dermoscopic method in the diagnosis of pigmented skin lesions in patients from ®Hermanos Ameijeiras¼ Hospital, Havana City, Cuba during 2008

OBJETIVO: Determinar el valor diagnóstico del método dermatoscópico ®Lista Recapitulativa de los Tres Puntos de Soyer¼ (LRTPS) en el diagnóstico de las lesiones cutáneas pigmentadas en pacientes del Hospital Hermanos Ameijeiras (La Habana-Cuba) durante el año 2008. MATERIAL Y MÉTODOS: Se realizó un estudio descriptivo transversal con 102 pacientes que asistieron a la Consulta de Dermatoscopía en el Hospital ®Hermanos Ameijeiras¼ de Ciudad de la Habana, Cuba, en el año 2008 para caracterizar la relación de este método de diagnóstico dermatoscópico y el comportamiento biológico de las lesiones cutáneas pigmentadas en el período estudiado. Se calcularon las tasas de sensibilidad y especificidad del método para el puntaje extremo de las lesiones y de las proporciones de malignidad / benignidad para las puntuaciones intermedias. RESULTADOS: La Lista de los Tres Puntos se comportó como un confiable método de alta sensibilidad y especificidad para el diagnóstico de benignidad de las lesiones con puntuación de cero. La sensibilidad para el diagnóstico de malignidad de lesiones con puntuación de tres fue baja, mientras que la especificidad fue alta. Existieron lesiones benignas y malignas con puntuación de 1 y 2, siendo mayor la proporción de lesiones benignas en el primer grupo y de lesiones malignas en el segundo grupo. CONCLUSIÓN: El método demuestra ser una herramienta útil y sencilla para determinar elcomportamiento biológico de las lesiones cutáneas pigmentadas.

OBJECTIVE: To determine the diagnostic value of dermatoscopic method ®Value of the Soyer´s Three Point Checklist¼ in the diagnosis of pigmented skin lesions in patients from ®Hermanos Ameijeiras¼ Hospital (La Habana-Cuba) during 2008. MATERIAL AND METHODS: A descriptive and transversal study was carried out with 102 patients from dermoscopy consultation at ®Hermanos Ameijeiras¼ Hospital, Havana City, Cuba during the year 2008 to characterize the relationship between the diagnostic method and the biological behavior of the pigmented skin lesion in the period studied. The sensibility and specificity rate for the extreme pointed pigmented skin lesions were calculated and also the proportions between malignancy and benignity for the middle pointed lesions. RESULTS: The Three Point Checklist was taken as a reliable method of high sensibility and specificity for the diagnosis of the benignity of the lesion having cero-point. The sensibility to the malignancy diagnosis of three-points lesions was low mean while the specificity was high.There were malignant and benign lesions with one and two points, being higher the proportion of benign lesions in the first group and of malignant lesions in the second one. CONCLUSION: The method shows to be a useful and easy tool to determine the biological behavior of a pigmented skin lesion.