Publications by authors named "I Planas Toledano"

9 Publications

Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer.

Ann Oncol 2020 08 13;31(8):1001-1010. Epub 2020 May 13.

Department of Medicine and Research, German Breast Group, Neu-Isenburg; Centre for Haematology and Oncology Bethanien, Frankfurt, Germany.

Background: Alpelisib (α-selective phosphatidylinositol 3-kinase inhibitor) plus fulvestrant is approved in multiple countries for men and postmenopausal women with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer following progression on or after endocrine therapy. A detailed understanding of alpelisib's safety profile should inform adverse event (AE) management and enhance patient care.

Patients And Methods: AEs in the phase III SOLAR-1 trial were assessed in patients with and without PIK3CA mutations. The impact of protocol-specified AE-management recommendations was evaluated, including an amendment to optimize hyperglycemia and rash management.

Results: Patients were randomly assigned to receive fulvestrant plus alpelisib (n = 284) or placebo (n = 287). The most common grade 3/4 AEs with alpelisib were hyperglycemia (grade 3, 32.7%; grade 4, 3.9%), rash (grade 3, 9.9%), and diarrhea (grade 3, 6.7%). Median time to onset of grade ≥3 toxicity was 15 days (hyperglycemia, based on fasting plasma glucose), 13 days (rash), and 139 days (diarrhea). Metformin alone or in combination with other antidiabetic agents was used by most patients (87.1%) with hyperglycemia. Preventive anti-rash medication resulted in lower incidence (any grade, 26.7% versus 64.1%) and severity of rash (grade 3, 11.6% versus 22.7%) versus no preventative medication. Discontinuations due to grade ≥3 AEs were lower following more-detailed AE management guidelines (7.9% versus 18.1% previously). Patients with PIK3CA mutations had a median alpelisib dose intensity of 248 mg/day. Median progression-free survival with alpelisib was 12.5 and 9.6 months for alpelisib dose intensities of ≥248 mg/day and <248 mg/day, respectively, compared with 5.8 months with placebo.

Conclusions: Hyperglycemia and rash occurred early during alpelisib treatment, while diarrhea occurred at a later time point. Early identification, prevention, and intervention, including concomitant medications and alpelisib dose modifications, resulted in less severe toxicities. Reductions in treatment discontinuations and improved progression-free survival at higher alpelisib dose intensities support the need for optimal AE management. CLINICALTRIALS.

Gov Id: NCT02437318.
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http://dx.doi.org/10.1016/j.annonc.2020.05.001DOI Listing
August 2020

Intraprostatic Fiducials Compared with Bony Anatomy and Skin Marks for Image-Guided Radiation Therapy of Prostate Cancer.

Cureus 2017 Oct 12;9(10):e1769. Epub 2017 Oct 12.

Radiotherapy, Centre Jean Perrin.

Purpose Prostate motion occurs during radiotherapy for localized prostate cancer. We evaluated the input of intraprostatic fiducials for image-guided radiation therapy and compared it with bony anatomy and skin marks. Methods Eleven patients were implanted with three fiducial markers in the prostate. Daily sets of orthogonal kV-kV images were compared with digitally reconstructed radiography. Data were recorded for skin marks, bony anatomy, and fiducial markers. The variations were analyzed along three principal axes (left-right: LR, superoinferior: SI, and anteroposterior: AP). Results A total of 2,417 measures were recorded over 38 fractions of radiotherapy (76 Gy). Fiducial marker movements from bony anatomy were ≤ 5 mm for 84.2% (confidence interval: CI 95%±1.5), 91.3% (CI 95%±1.1), and 99.5% (CI 95%±0.4) of the measures along the AP, SI, and LR axes, respectively. Ninety-five percent of the shifts between a fiducial marker and the bony anatomy were < 8 mm in the AP and SI axes, and < 3 mm in the LR axis. Fiducial marker movements from skin marks were ≤ 5 mm for 64.8% (CI 95%±1.9), 79.2% (CI 95%±1.6), and 87.2% (CI 95%±1.3) of the measures along the AP, SI, and LR axes, respectively. Bony anatomy movements from skin marks were ≤ 5 mm for 84% (CI 95%±1.4), 92% (CI 95%±1.1), and 87% (CI 95%±1.3) of the measurements along the AP, SI, and LR axes, respectively. Conclusion Using fiducial markers provides better accuracy of repositioning of the prostate than using bony anatomy and skin marks for image-guided radiotherapy of prostate cancer.
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http://dx.doi.org/10.7759/cureus.1769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726731PMC
October 2017

Urinary tract infection and indwelling urinary catheters: prospective study in gynecological surgery with antibiotic prophylaxis.

Sao Paulo Med J 2015 Nov-Dec;133(6):517-20. Epub 2015 Oct 9.

Mother-Child Department, School of Medicine, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil.

Context And Objectives: Urinary tract infections are the most common cause of hospital-acquired infections, and the use of indwelling urinary catheters is a predisposing factor for their development. The aims of this study were to estimate the frequency of pre and postoperative bacteriuria, identify the microorganisms involved, count the colony-forming units, determine the antibiotic sensitivity profile and compare the results from pre and postoperative urinalyses among women undergoing gynecological surgery with implantation of a urinary catheter.

Design And Setting: Non-controlled prospective observational single-cohort epidemiological study carried out at a university hospital.

Methods: Urine samples were collected before and 24 hours after catheterization for urinalysis, culturing and antibiotic sensitivity testing. Pre and postoperative urinalyses were compared using Wilcoxon and McNemar non-parametric tests.

Results: Fifty-one women participated in the study. Escherichia coligrew in six preoperative samples (11.8%) and Klebsiella pneumoniae in one (1.9%), but bacterial growth did not occur in any postoperative sample. Urinalysis showed lower number of pus cells in the postoperative urine samples (P < 0.05). There were no differences in red blood cell counts or in the nitrite and leukocyte esterase tests, between the samples.

Conclusion: Bacteriuria was found in 13.7% of the preoperative samples. Gram-negative bacteria sensitive to most antibiotics were identified. In the postoperative samples, no bacterial growth was observed. Urinalysis only showed significant reduction of leukocyturia in the postoperative period.
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http://dx.doi.org/10.1590/1516-3180.2014.9071412DOI Listing
July 2016

[Partial delegation to radiation therapists of the control by onboard imaging of patient positioning].

Cancer Radiother 2013 Feb 18;17(1):34-8. Epub 2013 Jan 18.

Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 392, 63011 Clermont-Ferrand cedex 1, France.

Purpose: Daily set up of patients with prostate cancer using orthogonal kV/kV imaging and weekly set up control require 1h to 1h30 of off line revision by a radio-oncologist per day and per accelerator. The aim of this study was to evaluate the possibility to delegate this control to radiation therapists.

Material And Methods: The files of 33 patients (including 13 with prostate cancer) treated from November 2010 to February 2011 on a Varian™ Clinac IX accelerator with an OBI™ system were evaluated. Radiation therapists made the daily kV/kV imaging. Radiation therapists made the online control by kV/kV for patient repositioning and radio-oncologists made the offline reviews; the results were compared and analysed (seven radiation therapists and seven radio-oncologists). For an isocentre displacement of 5mm, the radiation therapist had to call the radio-oncologist to make a medical decision (treatment or patient displacement). The difference of measures and the concordance of decisions between radiation therapists and radio-oncologists were calculated.

Results: Five hundred and fifty-six measures were made for 33 treatments, including 226 measures for prostate cancer treatment. The difference of measures between radiation therapists and radio-oncologists was 3mm or less in 93.7% for all treatments and 96.2% for prostate cancer treatment. The concordance of decision between radiation therapists and radio-oncologists for measures up to 4mm was 97% (CI95±2%) vs. 57% (CI95±10%) for measures equal to or higher than 5mm (P<0.0001).

Conclusion: Radiation therapists are able to do daily set up using kV/kV on the bony structures of patients with prostate cancer, with a risk of disagreement higher than 3mm less than 4%. The weekly set up controls (different primaries) can be delegated to the radiation therapists, subject to an accurate procedure using a medical alert for a given threshold. Training and competence certification are required to secure the process.
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http://dx.doi.org/10.1016/j.canrad.2012.12.001DOI Listing
February 2013

Concurrent use of aromatase inhibitors and hypofractionated radiation therapy.

World J Radiol 2012 Jul;4(7):318-23

Cyrus Chargari, Pablo Castro-Pena, Ivan Toledano, Marc A Bollet, François Campana, Patricia De Cremoux, Alain Fourquet, Youlia M Kirova, Department of Radiation Oncology, Institut Curie, 75005 Paris, France.

Aim: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients.

Methods: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale.

Results: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed.

Conclusion: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.
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http://dx.doi.org/10.4329/wjr.v4.i7.318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419868PMC
July 2012