Active surveillance of metastatic renal cell carcinoma: Results from a prospective observational study (MaRCC).

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival. RESULTS: Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. CONCLUSIONS: AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.

Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study.

BACKGROUND: Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 tyrosine kinases. This open-label, crossover clinical study (AV-951-09-902) provided access to tivozanib for patients who progressed on sorafenib in TIVO-1, comparing tivozanib with sorafenib in patients with advanced renal cell carcinoma (RCC). METHODS: Patients enrolled in this single-arm, phase 2 crossover study were previously randomised to sorafenib on TIVO-1, progressed and then crossed over to tivozanib. Patients received tivozanib (1.5 mg/day orally; 3 weeks on/1 week off) within 4 weeks after their last sorafenib dose. FINDINGS: Crossover patients were exposed to tivozanib for a median of eight cycles. From the start of tivozanib treatment, median progression-free survival was 11.0 months (95% confidence interval [CI]: 7.3-12.7) and median overall survival was 21.6 months (95% CI: 17.0-27.6). Best overall response was partial response in 29 (18%) patients and stable disease in 83 (52%) patients, with a median duration of response of 15.2 and 12.7 months, respectively. About 77% of patients experienced adverse events, most frequently hypertension (26%), followed by diarrhoea (14%) and fatigue (13%); 53% of patients had treatment-related adverse events, including 24% grade ≥3. About 9% and 16% of patients had dose reductions and dose interruptions due to adverse events, respectively. A total of 30% of patients had serious adverse events, and 4% had treatment-related serious adverse events. INTERPRETATION: This crossover study of patients with advanced RCC demonstrated potent tivozanib anti-tumour activity. Safety and tolerability profiles were acceptable and consistent with the established adverse event profile of tivozanib.

Acantholippia seriphioides: chemical biodiversity of wild populations from the Cuyo region in Argentina / Acantholippia seriphioides: biodiversidad química de poblaciones silvestres de la región de Cuyo de la Argentina

Nineteen samples from the aerial parts in bloom of Acantholippia seriphioides (Verbenaceae) were collected in three provinces belonging to the Cuyo region of Argentina. The essential oils were obtained by hydrodistillation, yielding between 0.57 and 2.46 percent (v/w). On the basis of the 13 main compounds determined by GC-FID-MS, representing the 87.2 and 95.3 percent of the total identified, four chemotypes were determined: carvacrol, thymol, cis and trans-dihydrocarvone and linalool-geraniol. The co-occurrence of different chemotypes in a same population indicates that the sample collection must be carefully done with the aid of an in situ olfactory testing of the plants, since no morphological differences at first sight were observed among them. The results showed in this study suggest that the pattern of variations for this species exists throughout its natural distribution area...

Se colectaron 19 muestras de partes aéreas en floración de Acantholippia seriphioides (Verbenaceae) de tres provincias de la región de Cuyo de la Argentina. Los aceites esenciales fueron obtenidos por hidrodestilación, arrojando rendimientos entre 0.57 y 2.46 por ciento (v/p). A partir de la determinación por GC-FID-MS de los 13 compuestos principales, que representaban entre el 87.2 y 95.3 por ciento del total de los identificados, fueron determinados cuatro quimiotipos: carvacrol, timol, cis y trans-dihidrocarvona, y linalol-geraniol. La co-ocurrencia de diferentes quimiotipos en una misma población indica que la colecta debe ser realizada con la ayuda de un examen olfatorio in situ de la planta, ya que, a primera vista no se observan diferencias morfológicas entre ellas. Los resultados sugieren que el patrón de variación para esta especie existe en toda su área de distribución natural...

Clinical practice guidelines for the treatment of metastatic renal cell carcinoma: today and tomorrow.

In the U.S. and Europe, clinical practice guidelines for metastatic renal cell carcinoma have undergone several revisions as a result of the introduction of molecular-targeted therapies. Recently, the National Comprehensive Cancer Network (NCCN) and the European Association of Urology (EAU) published updated guidelines to reflect these new treatment approaches that provide greater efficacy and better tolerability than the previous standard of care, cytokine therapy with interleukin-2 or interferon-α. Recommendations are classified by line of therapy, Memorial Sloan-Kettering Cancer Center risk level for survival, and level of evidence. Although many similarities exist, levels of evidence between the NCCN and EAU guidelines have differing designations and definitions, and timing of updates varies. New research developments, such as identification of effective combinations of targeted agents, optimal regimens for sequential therapy, newly designed targeted agents, benefits in special populations, and identification of additional prognostic factors and biomarkers, will prompt continued updates and refinements of today's clinical practice guidelines, with the goal of providing physicians with the most up-to-date clinical consensus upon which to base treatment decisions. Because clinical trial populations may not represent real-life patient populations, recommendations should serve only as a guide and must be tailored to the needs of each patient.