ABSTRACT
PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.
Subject(s)
Breast Neoplasms , Piperazines , Pyridines , Receptor, ErbB-2 , Humans , Pyridines/therapeutic use , Pyridines/adverse effects , Pyridines/administration & dosage , Female , Piperazines/therapeutic use , Piperazines/administration & dosage , Piperazines/adverse effects , Middle Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Breast Neoplasms/metabolism , Aged , Adult , Male , Retrospective Studies , Receptor, ErbB-2/metabolism , Aged, 80 and over , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/administration & dosage , Progression-Free SurvivalABSTRACT
The influence of antifungal tetraconazole residues (either as an active substance or as a commercial formulation product) on the fermentative activity of Saccharomyces cerevisiae yeast was evaluated in pasteurized Garnacha red must by using laboratory-scale fermentation assays. The presence of this fungicide promoted a slight decrease in glucose consumption. Volatile fermentative-derived compounds were evaluated in deep. Statistically significant changes were found in methionol (with a mean decrease of around 24%), fatty acids (with increments ranged from 23% to 66%), and ethyl esters (with increases ranged from 23% to 145%) contents when grape musts were enriched with the commercial formulation at both contamination levels assayed. Based on protein mass fingerprinting analysis, it was possible to relate these variations on volatiles content with changes in the activity of several enzymes (Met3p, Met14p, Adh2p, Hmg1p, Erg5p, Erg6p, Erg11p, and Erg20p) involved in the secondary metabolism of yeasts.
Subject(s)
Chlorobenzenes/metabolism , Ergosterol/metabolism , Fungicides, Industrial/metabolism , Methionine/metabolism , Saccharomyces/metabolism , Triazoles/metabolism , Volatile Organic Compounds/metabolismABSTRACT
The impact of mepanipyrim (Mep) and its corresponding commercial formulation (Mep Form) on Saccharomyces cerevisiae metabolites was assessed, separately, by using laboratory-scale wine fermentation assays on pasteurized red must. The presence of Mep did not alter the fermentation course. With regard to volatiles formed at the intracellular level by fermenting yeast cells, Mep residues affected mainly the acetate and ethyl ester biochemical pathways. In particular, the target acetates showed a notorious increment, >90%, in presence of commercial Mep Form at the higher dose assayed. The addition of Mep and Mep Form, at both tested levels, highly increased ethyl caprylate (between 42 and 63%) and ethyl caprate (between 36 and 60%) contents as the same as their respective fatty acid precursors. No important effects were observed on colour and non-volatile pyranoanthocyanins, probably due to the low anthocyanin content characteristic of pasteurized musts.
Subject(s)
Pyrimidines/analysis , Saccharomyces cerevisiae/metabolism , Wine/analysis , Acetates/analysis , Anthocyanins/analysis , Caprylates/chemistry , Color , Fermentation , Food Analysis , Pasteurization , Vitis/chemistry , Volatile Organic Compounds/analysisSubject(s)
Clomiphene/adverse effects , Fertility Agents, Female/adverse effects , Fertilization in Vitro , Vision Disorders/chemically induced , Administration, Oral , Adult , Clomiphene/administration & dosage , Female , Fertility Agents, Female/administration & dosage , Follow-Up Studies , Humans , Time FactorsABSTRACT
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