A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).

BACKGROUND: Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. PATIENTS AND METHODS: This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. RESULTS: Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. CONCLUSION: This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. TRIAL NUMBER: NCT01830231.

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

A new scenario in metastatic renal cell carcinoma: a SOG-GU consensus.

BACKGROUND: This article describes and compares approved targeted therapies and the newer immunotherapy agents. MATERIALS AND METHODS: This article especially performs an in-depth review of currently available data for tivozanib, explaining its mechanism of action, its safety profile and its role as an efficacy drug in the management of renal cancer. RESULTS: Despite the fact that the treatment of advanced RCC has been dramatically modified in recent years, durable remissions are scarce and it remains a lethal disease. For first- and second-line therapy, there is now growing evidence to guide the selection of the appropriate treatment. CONCLUSIONS: Several TKIs are standard of care at different settings. Among those approved TKIs, tivozanib has similar efficacy than others with a better safety profile. The use of prognostic factors is critical to the selection of optimal therapy.

Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

BACKGROUND/AIM: First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. PATIENTS AND METHODS: This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. RESULTS: Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. CONCLUSION: Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

The effects of sea urchin grazing and drift algal blooms on a subtropical seagrass bed community.

Subtropical seagrass beds can be subject to relatively high levels of direct herbivory and large blooms of drift algae, both of which can have important effects on the floral and faunal components of the community. Caging experiments were used to investigate these factors in a Thalassia testudinum bed in Biscayne Bay, Florida. Abundance of sea urchins, Lytechinus variegatus, and drift algae was manipulated within the cages. Naturally occurring levels of urchin grazing do not appear to affect the T. testudinum population. With experimentally increased urchin densities in the winter, seagrass shoot density and aboveground biomass decreased significantly. Similar effects were not detected in the summer, indicating that the impact of grazing on T. testudinum is lessened during this time of year. Shoot density was more vulnerable to grazing than aboveground biomass. This may be a result of grazing-induced increases in seagrass productivity, in which the remaining shoots produce more or longer leaves. In the winter, drift algal blooms form large mats that cover the seagrass canopy. Under the normal grazing regime these algal blooms do not have significant negative effects on the seagrass. With increased grazing pressure, however, there is a synergistic effect of grazing and drift algae on seagrass shoot density. At intermediate urchin density (10 per m(-2)), cages without algae did not undergo significant decreases in shoot density, while those with algae did. At the high density of urchins, the number of seagrass shoots in cages both with and without algae decreased, but the effect was more pronounced for cages with algae. Invertebrate abundance at the field site was low relative to other seagrass beds. There were no discernible effects, either positive or negative, of urchin and algae manipulations on the sampled invertebrate community.

Prognostic significance of circulating tumor cells in advanced non-small cell lung cancer patients treated with docetaxel and gemcitabine.

PURPOSE: To evaluate the association in the change of circulating tumor cell (CTC) levels and clinical outcomes (PFS and OS) in patients with advanced non-small cell lung cancer (NSCLC) treated homogenously with docetaxel and gemcitabine administered every 2 weeks. METHODS: We prospectively evaluated 37 patients for CTC levels at baseline and after 2 months of chemotherapy (before third cycle). Detection was carried out with the CellSearch system. RESULTS: Nine of the 37 patients (24 %) had ≥2 CTCs at the baseline determination. Median progression-free survival (PFS) was 4.3 months (95 % CI 2.5-8.3) for patients with CTC 0-1 as compared to 9.4 months (95 % CI 1.2-12.2) for those with CTC ≥2 (p = 0.3506). Median overall survival (OS) was 8.1 (95 % CI 2.8-16.3) and 12.2 (95 % CI 1.4-12.2) months for patients with 0-1 CTCs and ≥2 CTCs, respectively (p = 0.7639). Patients with a second CTC quantification were classified as: group 1, CTC = 0-1 at baseline and CTC = 0-1 after second chemotherapy cycle (18 patients); group 2, CTC ≥2 at baseline and CTC = 0-1 after second determination (5 patients). Median PFS was 7.7 and 9.9 months for group 1 and group 2, respectively (p = 0.4467). CONCLUSIONS: CTCs ≥2 at baseline were detected only in 24 % of this group of patients with advanced NSCLC and poor performance status. No significant differences in PFS and OS between patients with or without CTCs at baseline were observed.

Design and analysis of multiple choice feeding preference data.

Traditional analyses of feeding experiments that test consumer preference for an array of foods suffer from several defects. We have modified the experimental design to incorporate into a multivariate analysis the variance due to autogenic change in control replicates. Our design allows the multiple foods to be physically paired with their control counterparts. This physical proximity of the multiple food choices in control/experimental pairs ensures that the variance attributable to external environmental factors jointly affects all combinations within each replicate. Our variance term, therefore, is not a contrived estimate as is the case for the random pairing strategy proposed by previous studies. The statistical analysis then proceeds using standard multivariate statistical tests. We conducted a multiple choice feeding experiment using our experimental design and utilized a Monte Carlo analysis to compare our results with those obtained from an experimental design that employed the random pairing strategy. Our experimental design allowed detection of moderate differences among feeding means when the random design did not.