Preclinical and clinical development of palbociclib and future perspectives

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib

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Preclinical and clinical development of palbociclib and future perspectives.

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.

Adenocarcinoma colorrectal: factores pronósticos de supervivencia en el tratamiento adyuvante con 5-Fluorouracilo-Levamisol (5FU-Lev) / Colorectal adenocarcinoma: survical prognostic factors of the adjuvant treatment with 5-fluorouracil-levamisole (5FU-LEV)

- Propósito: Valoración de la supervivencia global (SG) y libre de enfermedad (SLE) a 5 años y estudio de los factores pronósticos de los pacientes operados, con finalidad curativa, de adenocarcinoma colorrectal estadios II y III, que recibieron tratamiento adyuvante con 5FU-LEV.- Material y métodos: ciento veintiséis pacientes tratados con esquema 5FU-LEV durante 12 meses, entre septiembre de 1990 y noviembre de 1997.- Resultados: La SG a los 5 años es de 68.3 por ciento y la SLE de 54 por ciento. El número de ganglios afectos por el tumor y la afectación vásculo-linfática y perineural, han resultado factores pronósticos significativos tanto en la SLE como en SG a los 5 años. La existencia de obstrucción intestinal tan sólo resulta factor pronóstico significativo en la SLE a los 5 años.- Conclusiones: los resultados que presentamos son semejantes a otras grandes series conocidas, tanto en supervivencia global y libre de enfermedad como en el estudio univariante de los factores pronósticos. La afectación ganglionar continúa presentando significación pronóstica con el análisis multivariante (AU)