Total iron-binding capacity is a novel prognostic marker after curative gastrectomy for gastric cancer

Abstract

Background

Patients with gastric cancer (GC) are affected by changes in iron status. Before surgery, GC patients are likely to have iron-deficiency anemia; and after gastrectomy, patients suffer from low nutritional status and low iron. This study investigated preoperative iron status associated with prognosis after curative gastrectomy for gastric cancer.

Methods

We evaluated preoperative serum hemoglobin (Hgb), Fe and total iron-binding capacity (TIBC) in 298 patients who underwent curative gastrectomy for GC without preoperative chemotherapy, and analyzed these factors' associations with prognosis after surgery.

Results

Of the 298 patients, 129 (43.2%) had low Hgb levels, and 33 (11.1%) had low TIBC (< 260 µg/dl) that was not associated with Hgb or Fe level. Patients with low TIBC were significantly associated with older age (≥ 65 years old; P = 0.0085), low albumin (< 3.9 g/dl; P = 0.0388) and high CRP (≥ 0.15 mg/dl; P = 0.0018) in multivariate analysis. Low Fe (< 60 µg/dl) was not associated with disease-free survival (DFS) or overall survival (OS); however, low Fe was associated with longer cancer-specific survival in Stage III GC patients (P = 0.0333). Both low Hgb and low TIBC were significantly associated with shorter DFS (Hgb: P = 0.0433; TIBC: P < 0.0001) and shorter OS (Hgb: P = 0.0352; TIBC: P < 0.0001). Low TIBC were significantly associated with shorter DFS (HR 2.167, 95% CI 1.231–3.639, P = 0.0086) and shorter OS (HR 2.065, 95% CI 1.144–3.570, P = 0.0173) in multivariate Cox hazard regression analysis.

Conclusions

Preoperative serum TIBC level of GC patients who undergo curative gastrectomy is a novel prognostic marker in univariate and multivariate analyses.

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Awareness of HPV and Cervical Cancer Prevention Among University Health Sciences Students in Cyprus

Abstract

Cervical cancer is preventable; however, despite the existence of primary and secondary means of prevention, its incidence is still higher in certain socioeconomic groups and countries, suggesting gaps in cervical cancer prevention. The objective of this study was to evaluate the knowledge and awareness of health sciences university students in Cyprus regarding HPV and cervical cancer in order to better guide the future development of educational programs to improve cervical cancer prevention. This was a cross-sectional study of 178 university health sciences students in Cyprus using a validated questionnaire on HPV and cervical cancer prevention. Analysis of the completed questionnaires revealed moderate levels of knowledge and awareness with an overall mean score of 23.32 out of 33 on HPV and 8.12 out of 13 on cervical cancer, a score of 9.25 out of 14 on HPV vaccines, and a score of 5.93 out of 9 on cervical cancer screening. Older students achieved higher scores compared to younger students (mean score of 6.76 for 18–22 years old, 9.44 for 23–28 years old, and 10.25 for 29–38 years old; p < 0.001). The study found several gaps in the students' knowledge and awareness on cervical cancer prevention. We suggest the design of education programs targeting this population possibly by incorporation of cervical cancer prevention education within students' curriculum to increase knowledge such that the spread of the virus is minimized and these health sciences students are prepared to educate their communities as part of their future practice in health professions.

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Awareness of HPV and Cervical Cancer Prevention Among University Health Sciences Students in Cyprus

Abstract

Cervical cancer is preventable; however, despite the existence of primary and secondary means of prevention, its incidence is still higher in certain socioeconomic groups and countries, suggesting gaps in cervical cancer prevention. The objective of this study was to evaluate the knowledge and awareness of health sciences university students in Cyprus regarding HPV and cervical cancer in order to better guide the future development of educational programs to improve cervical cancer prevention. This was a cross-sectional study of 178 university health sciences students in Cyprus using a validated questionnaire on HPV and cervical cancer prevention. Analysis of the completed questionnaires revealed moderate levels of knowledge and awareness with an overall mean score of 23.32 out of 33 on HPV and 8.12 out of 13 on cervical cancer, a score of 9.25 out of 14 on HPV vaccines, and a score of 5.93 out of 9 on cervical cancer screening. Older students achieved higher scores compared to younger students (mean score of 6.76 for 18–22 years old, 9.44 for 23–28 years old, and 10.25 for 29–38 years old; p < 0.001). The study found several gaps in the students' knowledge and awareness on cervical cancer prevention. We suggest the design of education programs targeting this population possibly by incorporation of cervical cancer prevention education within students' curriculum to increase knowledge such that the spread of the virus is minimized and these health sciences students are prepared to educate their communities as part of their future practice in health professions.

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Presurgical pazopanib for renal cell carcinoma with inferior vena caval thrombus: a single-institution study

The aim of this study was to investigate the clinical benefit of presurgical therapy with pazopanib in renal cell carcinoma (RCC) patients with a tumor thrombus extending to a high level in the vena cava. A retrospective review was performed for seven consecutive patients with RCC and tumor thrombus involving the vena cava above the hepatic vein (level 3–4, Mayo Clinic classification) treated with pazopanib without initial cytoreductive nephrectomy at our institution. The effect of pazopanib was assessed in terms of the primary site response, thrombus diameter, and height (before and after treatment) on computed tomography or MRI. The tumor thrombus level before the induction of pazopanib was 3 in one patient and 4 in the remaining six patients. After pazopanib, shrinkage of the primary site and thrombus diameter and length were observed in all patients except one (with a rhabdoid tumor). The mean decreases of primary tumor diameter, tumor thrombus diameter, and length were 14, 9, and 31 mm, respectively. The tumor thrombus level decreased in three (43%) patients and remained stable in the remaining patient. Our findings suggest that presurgical treatment with pazopanib may shrink the tumor thrombus and decrease the surgical invasiveness in RCC patients with a high-level tumor thrombus. Correspondence to Tomoaki Terakawa, PhD, MD, Department of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuoku, Kobe 650-0017, Hyogo Prefecture, Japan Tel: +81 78 382 6155; fax: +81 78 382 6169; e-mail: daatera0804@hotmail.com Received October 17, 2017 Accepted March 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Presurgical pazopanib for renal cell carcinoma with inferior vena caval thrombus: a single-institution study

The aim of this study was to investigate the clinical benefit of presurgical therapy with pazopanib in renal cell carcinoma (RCC) patients with a tumor thrombus extending to a high level in the vena cava. A retrospective review was performed for seven consecutive patients with RCC and tumor thrombus involving the vena cava above the hepatic vein (level 3–4, Mayo Clinic classification) treated with pazopanib without initial cytoreductive nephrectomy at our institution. The effect of pazopanib was assessed in terms of the primary site response, thrombus diameter, and height (before and after treatment) on computed tomography or MRI. The tumor thrombus level before the induction of pazopanib was 3 in one patient and 4 in the remaining six patients. After pazopanib, shrinkage of the primary site and thrombus diameter and length were observed in all patients except one (with a rhabdoid tumor). The mean decreases of primary tumor diameter, tumor thrombus diameter, and length were 14, 9, and 31 mm, respectively. The tumor thrombus level decreased in three (43%) patients and remained stable in the remaining patient. Our findings suggest that presurgical treatment with pazopanib may shrink the tumor thrombus and decrease the surgical invasiveness in RCC patients with a high-level tumor thrombus. Correspondence to Tomoaki Terakawa, PhD, MD, Department of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuoku, Kobe 650-0017, Hyogo Prefecture, Japan Tel: +81 78 382 6155; fax: +81 78 382 6169; e-mail: daatera0804@hotmail.com Received October 17, 2017 Accepted March 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A Randomized Comparison Between Interscalene and Small-Volume Supraclavicular Blocks for Arthroscopic Shoulder Surgery

Background and Objectives This randomized trial compared ultrasound (US)–guided interscalene block (ISB) and small-volume supraclavicular block (SCB) for arthroscopic shoulder surgery. We hypothesized that SCB would provide equivalent analgesia to ISB 30 minutes after surgery without the risk of hemidiaphragmatic paralysis (HDP). Methods All patients received an US-guided intermediate cervical plexus block. In the ISB group, US-guided ISB was performed with 20 mL of levobupivacaine 0.5% and epinephrine 5 μg/mL. In the SCB group, US-guided SCB was carried out using 20 mL of the same local anesthetic agent: 3 and 17 mL were deposited at the "corner pocket" (ie, intersection of the first rib and subclavian artery) and posterolateral to the brachial plexus, respectively. A blinded investigator assessed ISBs and SCBs every 5 minutes until 30 minutes using a composite scale that encompassed the sensory function of the supraclavicular nerves, the sensorimotor function of the axillary nerve, and the motor function of the suprascapular nerve. We considered the blocks complete if, at 30 minutes, a composite score equal or superior to 6 points (out of 8 points) was achieved. Thus, onset time was defined as the time required to reach a minimal composite score of 6 points. The blinded investigator also assessed the presence of HDP at 30 minutes with US. Subsequently, all patients underwent general anesthesia. Postoperatively, a blinded investigator recorded pain scores at rest at 0.5, 1, 2, 3, 6, 12, and 24 hours. Patient satisfaction at 24 hours, consumption of intraoperative and postoperative narcotics, and opioid-related adverse effects were also tabulated. Results Both groups displayed equivalent postoperative pain scores at 0.5, 1, 2, 3, 6, 12, and 24 hours. Interscalene blocks resulted in a higher incidence of HDP (95% vs 9%; P

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Effective Dose of Intravenous Dexmedetomidine to Prolong the Analgesic Duration of Interscalene Brachial Plexus Block: A Single-Center, Prospective, Double-Blind, Randomized Controlled Trial

Background and Objectives Intravenous (IV) dexmedetomidine (DEX) is reported to prolong the analgesic duration after single-shot interscalene brachial plexus block (ISBPB). However, the effective analgesic dose of IV DEX remains undetermined. Therefore, we aimed to elucidate the clinically relevant dose of IV DEX to prolong the analgesic duration of ISBPB. Methods Seventy-two patients scheduled for arthroscopic shoulder surgery received ISBPB with 15 mL of 0.5% ropivacaine with 1:200,000 epinephrine and were randomly assigned to 1 of 4 groups (n = 18, each): (1) IV normal saline (control), (2) IV DEX 0.5 μg/kg (DEX 0.5), (3) IV DEX 1.0 μg/kg (DEX 1.0), and (4) IV DEX 2.0 μg/kg (DEX 2.0). The primary outcome was time to the first pain at surgical site. Results The median (interquartile range) duration of analgesia was significantly prolonged for the DEX 2.0 (874 minutes [727–1153 minutes]) compared with 656 minutes (590–751 minutes), 703 minutes (644–761 minutes), and 696 minutes (615–814 minutes) for the control, DEX 0.5 and DEX 1.0 groups, respectively (P = 0.001, P = 0.008, and P = 0.003, respectively). Postoperative cumulative IV morphine equivalent consumption at 24 hours was significantly lower in the DEX 2.0 compared with the control, DEX 0.5 and DEX 1.0 groups (P

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Perineural Versus Systemic Dexamethasone in Front-Foot Surgery Under Ankle Block: A Randomized Double-Blind Study

Background and Objectives Among the different adjuvants, dexamethasone is one of the most accepted to prolong the effect of local anesthetics. This study aims to determine the superiority of perineural over systemic dexamethasone administration after a single-shot ankle block in metatarsal osteotomy. Methods We performed a prospective, double-blind, randomized study. A total of 100 patients presenting for metatarsal osteotomy with an ankle block were randomized into 2 groups: 30 mL ropivacaine 0.375% + perineural dexamethasone 4 mg (1 mL) + 2.5 mL of systemic saline solution (PNDex group, n = 50) and 30 mL ropivacaine 0.375% + 1 mL of perineural saline solution + intravenous dexamethasone 10 mg (2.5 mL) (IVDex group, n = 50). The primary end point was the duration of analgesia defined as the time between the performance of the ankle block and the first administration of rescue analgesia with tramadol. Results Time period to first rescue analgesia with tramadol was similar in the IVDex group and the PNDex group. Data are expressed as mean (SD) or median (range). Duration of analgesia was 23.2 (9.5) hours in the IVDex group and 19 (8.2) hours in the PNDex group (P = 0.4). Consumption of tramadol during the first 48 hours was 0 mg (0–150 mg) in the IVDex group versus 0 mg (0–250 mg) in the PNDex group (P = 0.59). Four (8%) and 12 (24%) patients reported nausea or vomiting in the IVDex group and the PNDex group, respectively (P = 0.03). Conclusions In front-foot surgery, perineural and systemic administrations of dexamethasone are equivalent for postoperative pain relief when used as an adjuvant to ropivacaine ankle block. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT02904538. Address correspondence to: Philippe Marty, MD, Department of Anesthesia, Clinique Médipôle Garonne, 31036, Toulouse, France (e-mail: philippemarty@hotmail.com). Accepted for publication November 20, 2017. The authors declare no conflict of interest. Support was provided solely from institutional and department sources from Department of Anesthesiology, Clinique Médipôle Garonne, Toulouse, France. This work should be attributed to the Department of Anesthesiology, Clinique Médipôle Garonne, Toulouse, France. Authors' contributions: O.R., B.Basset, C.V., and M.C.M. performed all regional anesthesia. P.M. and F.F. wrote the manuscript. C.M., M.M., and M.C. participated in the design of the study. B.Bataille performed the statistical analysis. A.D. participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Practice Management: Successfully Guiding Your Group into the Future

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




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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.

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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.



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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).



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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.



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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.



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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.



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