Practice Management: Successfully Guiding Your Group into the Future

Publication date: Available online 7 April 2018
Source:Anesthesiology Clinics
Author(s): Lee A. Fleisher




https://ift.tt/2qgrlC3

Septate Uterus in a Girl with Rubinstein–Taybi Syndrome

Rubinstein–Taybi syndrome is an extremely rare plurimalformative condition that can affect any organ. However, reports regarding gynecological problems are unusual. We report the first case of a septate uterus in an adolescent with this syndrome, in agreement with the American Society for Reproductive Medicine (ASRM) and the Congenital Uterine Malformations by Expert (CUME) criteria for uterine septum. Additional studies are required to determine whether there is an increased frequency of müllerian duct anomalies with the condition. Our report extends the data on the clinical phenotype associated with Rubinstein–Taybi syndrome.

https://ift.tt/2Es8qZi

Immunotherapy phase I trials in patients Older than 70 years with advanced solid tumours

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): H. Herin, S. Aspeslagh, E. Castanon, V. Dyevre, A. Marabelle, A. Varga, S. Postel Vinay, J.M. Michot, V. Ribrag, A. Gazzah, R. Bahleda, O. Mir, C. Massard, A. Hollebecque, J.C. Soria, C. Baldini
BackgroundThe development of immune checkpoint blocker development brings new hope in older patients (OPs) because of clinical efficacy and low toxicity. Clinical indications are rising steadily, but very few data are available in the geriatric population where comorbidities, reduced functional reserve and immunosenescence may affect efficacy and tolerance.MethodsAll cases of patients enrolled in immunotherapy phase I trials between January 2012 and December 2016 in the Drug Development Department (DITEP) at Gustave Roussy were retrospectively reviewed. Case–control analysis was performed in OPs (patients ≥ 70 years) matched to younger patients (YPs) (patients < 70 years) by trial and treatment dose. We compared cumulative incidence, grade and type of immune-related adverse events (IrAEs) and survival outcomes.ResultsAmong the 46 OPs and the 174 YPs enrolled in 14 phase I/II trials, 10 (22%) and 23 (13%) patients experienced grade III–IV IrAEs. Cumulative incidence of grade I–II IrAEs was significantly higher in OPs than YPs (p < 0.05). No significant difference was observed between the two groups for grade III–IV IrAEs (p = 0.50). Older age was not associated with lower dose intensity of treatment (p = 0.14). No significant difference was observed between OPs and YPs in median progression-free survival (hazards ratio 1.41, 95% confidence interval [CI] [0.94–2.11] p = 0.09) or median overall survival (HR 0.92, 95% CI [0.61–1.39] p = 0.77).ConclusionImmune checkpoint blockade appears to be an acceptable treatment option for OPs in the setting of phase I trials.



from Cancer via ola Kala on Inoreader https://ift.tt/2IDBMGn
via IFTTT

Phase I feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): Claire Bonneau, Gilles Paintaud, Olivier Trédan, Coraline Dubot, Céline Desvignes, Véronique Dieras, Sophie Taillibert, Patricia Tresca, Isabelle Turbiez, Jacques Li, Christophe Passot, Fawzia Mefti, Emmanuelle Mouret-Fourme, Emilie Le Rhun, Maya Gutierrez
PurposeLeptomeningeal carcinomatosis (MC) is commonly associated with HER2-positive breast cancer (HER2-BC), with a poor prognosis and no standardised treatment. We conducted a phase I dose-escalation study of intrathecal (IT) administration of trastuzumab in HER2-BC patients with MC to determine the maximum tolerated dose (MTD), which was based on both the achievement of a trastuzumab intra-cerebrospinal fluid concentration close to a conventional therapeutic plasma concentration (30 mg/L) and/or dose-limiting toxicity (DLT).MethodsThe protocol planned IT administration of trastuzumab (30 mg, 60 mg, 100 mg or 150 mg dose levels) once a week, over the course of at least 4 weeks. Sixteen patients with MC from HER2-BC received IT trastuzumab. Intra-cerebrospinal fluid samples were obtained before each injection for pharmacokinetics.ResultsWe did not observe DLT of IT trastuzumab. Eleven patients had no toxicity attributed to IT trastuzumab. For 60 mg or higher dose levels, minor toxicities attributed to IT trastuzumab included headache (2 patients), nausea (2 patients), vomiting (1 patient), cervical pain (1 patient) and peripheral neuropathy (1 patient). Two patients experienced immediate toxicity including headache or vomiting. The mean residual intra-cerebrospinal fluid concentration of trastuzumab was 27.9 mg/L for the 150 mg dose level. Three patients achieved a clinical response, seven patients had stable disease and four patients had progressive disease.ConclusionsThe MTD and recommended phase II weekly dose of IT trastuzumab in patients with HER2-BC and MC is 150 mg. A phase II trial using this dose regimen in MC from HER2-BC is ongoing.Registration identificationClinicalTrials.gov Identifier: NCT01373710 (https://ift.tt/2IAB1Op).



from Cancer via ola Kala on Inoreader https://ift.tt/2H5A17W
via IFTTT

Treatment decisions and the impact of adverse events before and during extended endocrine therapy in postmenopausal early breast cancer

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): Erik J. Blok, Judith R. Kroep, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Hein Putter, Gerrit-Jan Liefers, Johan W.R. Nortier, Emiel J.Th. Rutgers, Caroline M. Seynaeve, Cornelis J.H. van de Velde
BackgroundExtended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment discontinuation, and how this influenced survival outcome.MethodsIn the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive early breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for early treatment discontinuation and the effect of early treatment discontinuation on disease-free survival (DFS).ResultsNodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with early treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with early treatment discontinuation. Early treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76–1.37).ConclusionsIn this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to early treatment discontinuation, with no effect on DFS.



from Cancer via ola Kala on Inoreader https://ift.tt/2H6eXyc
via IFTTT

Bladder cancer survival: Women better off in the long run

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): Bettina Kulle Andreassen, Tom Kristian Grimsrud, Erik Skaaheim Haug
AimMortality among patients with bladder cancer is usually reported to be higher for women than men, but how the risk differs and why remain largely unexplained. We also described gender-specific differences in survival for patients with bladder cancer and estimated to what extent they can be explained by differences in T-stage distribution at the first diagnosis.MethodsThe present study comprised all 15,129 new cases of histologically verified invasive and non-invasive urothelial carcinoma of the urinary bladder diagnosed between 1997 and 2011 as registered in the Cancer Registry of Norway. Gender-specific excess mortality risk rates and risk ratios were calculated based on a flexible parametric relative survival model adjusting for T-stage and age, allowing the effect of gender to vary over time. We also present gender-specific relative survival curves for different T-stage patterns adjusted for age.ResultsRisk rates were significantly higher for women than men up to 2 years after bladder cancer diagnosis, particularly for muscle-invasive cancers. Thereafter, risk rates appeared to be higher in men. Adverse T-Stage distribution in women explained half of the unfavourable survival difference in female patients 2 years after diagnosis.ConclusionThe common view of worse bladder cancer prognosis in women than in men needs to be revised. Norwegian women have a less favourable prognosis solely within the first 2 years after diagnosis, particularly when diagnosed with a muscle-invasive tumour; parts of this discrepancy can be attributed to more severe initial diagnoses in women.



from Cancer via ola Kala on Inoreader https://ift.tt/2ID4c3F
via IFTTT

Efficacy of cabazitaxel rechallenge in heavily treated patients with metastatic castration-resistant prostate cancer

Publication date: Available online 7 April 2018
Source:European Journal of Cancer
Author(s): Constance Thibault, Jean-Christophe Eymard, Alison Birtle, Michael Krainer, Giulia Baciarello, Aude Fléchon, Sylvestre Le Moulec, Dominique Spaeth, Brigitte Laguerre, Orazio Caffo, Jean-Laurent Deville, Phillipe Beuzeboc, Ali Hasbini, Marine Gross-Goupil, Carole Helissey, Mostefa Bennamoun, Anne-Claire Hardy-Bessard, Stéphane Oudard
BackgroundTreatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC.Patients and methodsClinical data were collected retrospectively in 17 centres in Europe. Eligible patients had undergone rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT and CABA, in any order). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method. Data on toxicities were collected.ResultsA total of 69 of 562 patients (Eastern Cooperative Oncology Group performance status 0–1 69%) were rechallenged with CABA (25 mg/m² q3w, 58%; 20 mg/m² q3w, 27.5%; other, 14.5%) for 1–10 (median 6) cycles; 76.8% received prophylactic granulocyte colony-stimulating factor. Median radiological or clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3–15.7) from the first CABA rechallenge cycle, 59.9 months (47.8–67.1) from the first life-extending therapy in mCRPC and 78.3 months (66.4–90.7) from mCRPC diagnosis. Best clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of prostate-specific antigen decreased by ≥ 50% in 24% of patients at rechallenge (71% with initial CABA). There was no grade ≥III peripheral neuropathy or nail disorders.ConclusionsCABA rechallenge may be a treatment option without cumulative toxicity in heavily pretreated patients with mCRPC who are still fit and had a progression >3 months after the last CABA injections.



from Cancer via ola Kala on Inoreader https://ift.tt/2H83Kx8
via IFTTT