Analysis of data from the PALOMA-3 trial confirms the efficacy of palbociclib and offers alternatives for novel assessment of clinical trials.

PURPOSE: There remains a need for novel therapies for patients with metastatic breast cancer (MBC). We explore the use of a novel biomarker of survival that could potentially expedite the testing of novel therapies. METHODS: We applied a tumor regression-growth model to radiographic measurement data from 393 women with MBC enrolled in PALOMA-3 examining efficacy of palbociclib in disease that had progressed on previous endocrine therapy. 261 and 132 women were randomized to fulvestrant plus palbociclib or placebo, respectively. We estimated rates of regression (d) and growth (g) of the sensitive and resistant fractions of tumors, respectively. We compared the median g of both arms. We examined the relationship between g and progression-free and overall survival (OS). RESULTS: As in other tumors, g is a biomarker of OS. In PALOMA-3, we found significant differences in g among patients with tumors sensitive to endocrine therapy but not amongst resistant tumors, emulating clinical trial results. Subgroup analysis found favorable g values in visceral metastases treated with palbociclib. Palbociclib efficacy demonstrated by slower g values was evident early in the trial, twelve weeks after the first 28 patients had been enrolled. CONCLUSION: Values of g, estimated using data collected while a patient is enrolled in a clinical trial is an excellent biomarker of OS. Our results correlate with the survival outcomes of PALOMA-3 and argue strongly for using g as a clinical trial endpoint to help inform go/no-go decisions, improve trial efficiency, and deliver novel therapies to patients sooner.

Impact on clinical practice of the implementation of guidelines for the toxicity management of targeted therapies in kidney cancer. The protect-2 study.

BACKGROUND: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. METHODS: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. RESULTS: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7% out of 966 post-implementation cycles compared with 23.1% out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33% pre-implementation vs. 44.5% post-implementation cycles; p < 0.0001), diarrhea (74.0% vs. 80.5%; p = 0.011) and dyslipemia (25.0% vs. 44.6%; p < 0.001). CONCLUSIONS: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction.

Analysis of cellular objects through diffraction images acquired by flow cytometry.

It was found that the diffraction images acquired along the side scattering directions with objects in a cell sample contain pattern variations at both the global and local scales. We show here that the global pattern variation is associated with the categorical size and morphological heterogeneity of the imaged objects. An automated image processing method has been developed to separate the acquired diffraction images into three types of global patterns. Combined with previously developed method for quantifying local texture pattern variations, the new method allows fully automated analysis of diffraction images for rapid and label-free classification of cells according to their 3D morphology.

A novel method of diffraction imaging flow cytometry for sizing microspheres.

We report a novel method of diffraction imaging flow cytometry to measure and analyze size distribution of microspheres. An automated and robust image processing software based on the short-time-Fourier-transform algorithm has been developed to analyze the characteristic and spatially varying oscillations of side scatters recorded as a diffraction image. Our results demonstrate that the new method allows accurate and rapid determination of single microspheres' diameters ranging from 1 to 100 µm. The capacity for analysis of light scattering by two-sphere aggregates has been demonstrated but analytical tools for characterization of aggregates by multiple microspheres remain to be developed.

Parasitosis y cáncer / Parasitosis and cancer

Los tratamientos de las enfermedades tumorales o de las parasitarias presentanciertos aspectos químico-farmacéuticos comunes. En este trabajo se expone unestudio comparativo entre las estructuras químicas que muestran zonas o funcionescomunes de cada grupo terapéutico. La conclusión del mismo es que, cuandose dispone de un compuesto activo en una de estas áreas, merece la pena probarloen la otra

The treatments of neoplastic and parasitary diseases present some commonchemical and pharmacological profiles. In this paper, a comparative study betweenchemical structures of each therapeutic group that have similar functions is shown. The conclusion is that every new chemical with activity in any of these areas is asuitable candidate to be tested in the other one

Talidomida: una visión nueva de un tóxico antiguo / Thalidomide: a new view of an old toxic

Desde que a principios de los años 60 la talidomida fuera retirada del mercadodebido a su acción teratogénica, este fármaco ha sido ampliamente estudiado,encontrándose en él propiedades terapéuticas que han despertado nuevamente elinterés por esta molécula. Recientemente, la FDA ha aprobado su empleo en eltratamiento de ENL (Erythema Nodosum Leprosum), una manifestación aguda dela lepra. Además, actualmente se encuentra en ensayos clínicos (fase II/III) enmieloma múltiple, cáncer de mama, próstata, riñón y pulmón, mostrando buenosresultados. En este artículo se ofrece una visión general de las propiedades de latalidomida, haciendo especial hincapié en su acción inhibitoria de la angiogénesis,que podría ser responsable, al menos en parte, de su actividad antineoplásica yteratogénica

Since the early 60s, when thalidomide was withdrawn from markets, this drug ;;has been widely studied due to its teratogenic activity. The finding of new therapeutic properties has raised a new interest in this molecule, and recently the FDA ;;has approved its use in the treatment of ENL (Erythema Nodosum Leprosum), an ;;acute manifestationof leprae. Besides, thalidomide is nowadays going through clinical ;;assays (PhaseII/III) in multiple myeloma, breast, prostate, kidney and lung ;;tumours, showing good results. This article offers an overview of thalidomide ;;properties focusing on its inhibition of angiogenesis, which would be responsible, ;;at least partially, of its antineoplastic and teratogenic activity