Need For Premedication Research Articles

Burden of cremophor-related paclitaxel therapy on patients with ovarian cancer: A patient focused study from the United Kingdom, Germany, and Spain.

e17576 Background: Cremophor EL (CrEL) is a solubilizer used in paclitaxel and is associated with side effects (i.e., hypersensitivity reactions, peripheral neuropathy). Current CrEL-containing therapies require long infusion times (2-4 hours) and pre-medication with steroids to manage these side-effects. However, the holistic burden of CrEL on patients is not well studied. This study aimed to characterize the burden associated with CrEL-paclitaxel treatment on patients with ovarian cancer, including clinical, safety, and quality of life (QoL) implications. Methods: This quantitative, Institutional Review Board (IRB) approved, cross-sectional survey of patients (≥18 years) who received ≥3 cycles of CrEL-containing paclitaxel within the prior 6 months was conducted in UK, Germany, and Spain in 2021. Data were collected via a web-enabled instrument including a screener, questionnaire, and validated Functional Assessment of Cancer Therapy (FACT)-Taxane scale. Results are reported overall for the 3 countries. Results: Of the 90 patients surveyed, the mean age was 38.8 years. Most patients reported improvement of QoL (77%), treatment effectiveness (77%), less need for pre-medications (74%), and manageable/less disruptive infusion times and schedules (71%) as extremely desirable treatment attributes. Prior to or during chemotherapy, 41% of patients reported receiving steroids. Most patients (71%) experienced 3-6 side effects related to ovarian cancer treatment. Of the patients that experienced neuropathy (27%), the side effect lasted for up to 1 week for 54% of patients, and over multiple cycles of treatment (> 3 weeks) for 13% of patients. Of the 82% of patients eligible to complete the FACT-Taxane scale, 62% were somewhat to very much bothered by the side effects of paclitaxel. Half of these patients reported tingling/numbness in their hands/feet, moderately or very often. Patients reported an average of 4.8 hours as the time taken for their travels to/from the infusion center and receive their medication. Additionally, 91% of patients needed caregiver support for an average of 16 hours per week. 51% of patients reduced their work hours due to treatment and 58% reported a substantial impact on work productivity. To cover treatment costs, 63% purchased supplemental insurance. Conclusions: The patient-reported burden of treatment associated with CrEL-containing paclitaxel is significant and complex. Multiple treatment side effects occur in most patients which are burdensome and can recur and/or persist with future treatment cycles. There is an unmet need for an effective therapy that reduces treatment burden for patients and improves tolerability through fewer side effects, a reduced need for premedication, and shorter infusion time.

Utilization of Alexandrite Laser for Hair Removal in Pediatric Auricular Reconstruction.

Auricular reconstruction with autologous rib cartilage involves using a soft tissue envelope to cover the cartilage framework. In patients with a low hairline, hair-bearing skin may be incorporated on the reconstructed ear, creating a difficult and conspicuous aesthetic problem. A retrospective chart review was conducted to summarize and share the experience of using the Candela GentleMax Pro 755-nm alexandrite laser system (Candela Corp) in children following auricular reconstruction. Nine patients received laser hair removal via the alexandrite laser system with good results. The number of completed sessions ranged from 1 to 5. The procedures were completed without the need for premedication or procedural sedation. Laser hair removal with an alexandrite laser system was safe, fast, and effective. With multistage auricular reconstruction, it was feasible to incorporate laser hair removal between the stages.

Nab-paclitaxel in Treatment of Metastatic Breast Cancer

Despite the development of new systems for the treatment of metastatic breast cancer (mBC), chemotherapy remains an integral and significant stage of treatment for any molecular tumor subtype. In accordance with modern concepts, the optimal strategy of therapy in the vast majority of cases of mBC is the sequential administration of cytostatics in mono modes. This approach allows long-term control of tumor growth, translating pathology into a chronic discharge and maintaining a high quality of life. The emergence of new drugs or innovative dosage forms of existing cytostatics expands the possibilities of treatment of this chronic disease and allows long-term control over the disease. One of such new options was nab-paclitaxel, nano-dispersed paclitaxel stabilized with albumin. This dosage form provides active transport of the drug through the vascular endothelium with the creation of its high concentration in the tumor tissue. Clinical studies comparing nab-paclitaxel with traditional taxanes (paclitaxel and docetaxel) demonstrated high efficacy and safety of the drug both in a wide population of patients and in individual subgroups, including patients previously treated with anthracycline taxane, cases with aggressive disease, lesions of visceral organs, elderly patients and others. In addition, due to its unique formula, the drug does not cause hypersensitivity reactions, differing from traditional These taxanes are easy to use and safe. The lack of need for premedication with dexamethasone allows it to be prescribed for such comorbidities as severe hypertension, diabetes mellitus, stomach ulcer and duodenal ulcer, etc., and also successfully combine it with inhibitors of control points of the immune response, which confidently removes the drug on arena of immuno-oncology.

Practical considerations and role of Daratumumab retreatment for relapsed refractory Multiple Myeloma

Daratumumab is a first-in-class anti-CD38 monoclonal antibody approved for multiple myeloma. Because of the incidence and severity of infusion-related reactions with initial doses, daratumumab is administered over 6.5 hours for the first dose. With the need for pre-medication and monitoring, patients are scheduled for a 10-hour infusion visit. In an attempt to improve patient experience as well as optimize clinic space, additional pre-medications have been added with the initial doses and rapid infusion rate has been introduced for subsequent doses.

Patient Preferences Regarding Chemotherapy in Metastatic Breast Cancer-A Conjoint Analysis for Common Taxanes.

Background: The purpose of this investigation was to explore patient perception regarding the importance of efficacy, toxicity, and logistics in the choice of regimen of taxane-based chemotherapy (CHT) for patients with metastatic breast cancer (MBC).Methods: This dual-center study analyzed data of 100 women diagnosed with MBC, who were asked for their preferences regarding chemotherapy by means of conjoint analysis. Included attributes were progression free survival (PFS), application form, time and frequency, need of premedication, risk of alopecia, fatigue, febrile neutropenia, and neuropathy. Furthermore, participants completed a questionnaire about their personal and medical history. Regression analyses were performed to identify factors that influence patient preference in terms of specific treatment choice.Results: Of 8 attributes, severe neutropenia was top priority for the majority of patients, followed by alopecia, neuropathy and PFS. When combining these patient preferences and the results of the questionnaire, patients' age as, well as, relationship status had significant impact on the importance of PFS. Moreover, longer travel time to the treatment center was significantly associated with preferences regarding PFS. Ranking by combination of respective part-worth values demonstrated nab-paclitaxel to be favored over paclitaxel and docetaxel.Conclusion: Side effects of CHT and PFS prove to be critical factors for patients affecting choice of treatment in MBC with severe neutropenia being top priority, followed by alopecia, neuropathy, and PFS. Age, commute time, and relationship status were identified as significant determinants of patient preference. Total utility calculation by combination of part-worth values ranked nab-paclitaxel as the most preferable taxane.

The Efficacy of External Rotation Method for The Reduction of Acute Anterior Shoulder Dislocation With and Without Greater Tuberosity Fracture

Introduction: Several methods of reduction technique have been described for the anterior dislocation of shoulder but none technique is said to be ideal. The aim of this study was to show the efficacy of external rotation method which could be safe and painless method for the reduction of the acute anterior shoulder dislocation with or without fracture of the greater tuberosity and to search the cause of failure of reduction.Objective: Objective of this study was to assess the efficacy of the external rotation method for reduction of acute anterior shoulder dislocation and to find the cause of failure of reduction.Methodology: All cases of anterior dislocation encountered in emergency department reduced by external rotation method by consultant orthopedic surgeon using basic emergency setting for resuscitation were included in the study. Fifty cases of shoulder dislocation was treated by this method and prospective evaluation done with regard to type of dislocation, the effectiveness of the procedure in achieving reduction, the need for pre-medication, the ease of performing reduction and complication if any.Results: Out of 50 cases, successful reduction was achieved in 42 patients. Premedication was not required in 36 successful reduction. Average time of reduction was 2 minutes in 30 patients and 5 minutes in 8 patients. Four Patients complained severe pain during reduction process. This method was not successful in 8 patients 2 of whom had displaced greater tuberosity fracture.Conclusion: The external rotation method is reliable and safe method for the reduction of acute anterior shoulder dislocation which can be performed relatively with less pain for both subcoracoid and subglenoid dislocation provided there is no displaced fracture of the greater tuberosity. BJHS 2018;3(2)6: 408-412.

Abstract P6-14-01: The effect trial: A randomized phase II trial evaluating two different doses of weekly (W) NAB-paclitaxel (NP) as first-line chemotherapy in older breast cancer (BC) patients (pts)

Abstract Background: W taxanes (T) are commonly used in the treatment of older BC pts, with neurotoxicity (NTX) and fatigue being dose-limiting toxicities with a possible negative impact on function. No prospective data exists on the safety and efficacy of W NP in this population. NP might be of particular value in older pts, due to no need for premedication with steroids and shorter time to recovery from neurotoxicity than conventional T, resulting in a reduced risk of exacerbation of comorbidities such as hypertension and diabetes, and possibly of functional decline (FD). Methods: Pts aged ≥ 65 years (y) with Her-2 negative or Her-2 positive (+), but contraindicated to anti-Her-2 therapy, advanced BC were randomized to receive NP as first-line chemotherapy at either 100 (Arm A) or 125 mg/m2 (Arm B), days 1, 8, 15 q 28. The primary end-point was event-free survival (EFS). An event was either disease progression (PD), death, or FD - defined as a decrease of at least 1 point from baseline values of activities of daily living (ADL) or instrumental ADL (IADL), deemed by the investigator as treatment-related and confirmed at the subsequent cycle. Secondary endpoints included progression-free survival (PFS), response rate (RR) in pts with measurable disease, and incidence of adverse events (AEs). Results: From January 2013 to September 2016, 160 pts were randomized in 15 Italian centres; all but 2 who never started NP were eligible for final analysis. Pts median age was 72y (range 65-84) in Arm A and 73y (range 65-88) in Arm B. Median ECOG performance status was 0 (range 0-2). Baseline IADL impairment was reported in 20 pts (25%) in both arms. >80% pts had ER+ tumors; 2 pts had HER2+ disease. Visceral disease was present in 71% (Arm A) and 70% (Arm B) of pts. Prior exposure to T in the neo/adjuvant setting was 14% (Arm A) and 13% (Arm B). Median number of delivered cycles of NP was 6 (range 1-28 in Arm A, and 1-22 in Arm B), with 3 pts still on treatment. Dose reductions were similarly reported (72% of pts Arm A, 78% of pts Arm B). At a median follow-up of 21 months (mos) (Interquartile range 14-28.4) 140 events were observed. Arm A/Arm B: PD n=53(67%)/n=52(66%); FD n=13(15%)/n=14(18%), death n=3(4%)n=5(6%). Outcomes data are reported in the following table: Outcomes Arm AArm BMedian EFS, mos (90% CI)6.2 (5.5-8.4)6.4 (5.8-7.7)Median PFS, mos (95% CI)8.3 (5.9-10.5)8.8 (7.4-10.3)RR (95% CI)37% (25-50)42% (30-54) Fatigue (Arm A: grade (G)2 29%, G3 11%; Arm B: G2 46%, G3 5%) and NTX (Arm A: G2 15%, G3 4%; Arm B: G2 28%, G3 8%) were the most frequently reported AEs. No G4 AEs were reported with the exception of neutropenia (1 pt in arm A) and leucopenia (3 pts in Arm A, 1 pt in arm B). 1 G5 (sepsis) was recorded in Arm B. NTX was reported as the reason for treatment discontinuation in 21 pts (13%) of whom 16 (21%) in arm B. Conclusion: Looking at classical study endpoints (PFS, RR), both doses of NP are active in older pts. However, 17% of pts had to stop treatment due to FD, assessed according to predefined criteria. Due to similar efficacy and reduced NTX, W NP 100 is the suggested dose to be used in older pts with advanced BC. Citation Format: Biganzoli L, Berardi R, Pedersini R, Minisini AM, Caremoli ER, Spazzapan S, Lima JS, Baldari D, Orlando L, Magnolfi E, Pistelli M, Brunello A, Zafarana E, Bernardo A, Leo S, Colleoni M, Donati S, De Placido S, Parolin V, Vitale S, Di Leo A, Puglisi F, Boni L, Cinieri S. The effect trial: A randomized phase II trial evaluating two different doses of weekly (W) NAB-paclitaxel (NP) as first-line chemotherapy in older breast cancer (BC) patients (pts) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-14-01.

Assessment of Antihistamines and Corticosteroids as Premedication in Rapid Drug Desensitization to Paclitaxel: Outcomes in 155 Procedures

In early clinical trials, infusion reactions during the administration of taxanes were managed using systematic premedication with antihistamines and corticosteroids before standard infusions. Consequently, these premedications are also administered before rapid drug desensitization (RDD) with taxanes. However, their role in RDD has not been studied. To assess the need for premedication with antihistamines and corticosteroids to prevent hypersensitivity reactions in RDD to paclitaxel. Over a 4-year period, we selected patients with confirmed hypersensitivity to paclitaxel (positive skin testing and/or drug provocation testing results) who had received paclitaxel through RDD. These patients were assigned to 2 prospective noninception cohorts: one cohort premedicated with antihistamine and corticosteroids and another cohort that was not. We assessed 66 paclitaxel-reactive patients, of whom 22 met the inclusion criteria. A total of 155 RDDs to paclitaxel were performed. There were no significant differences in tolerance to RDD between the cohorts. Administering systematic premedication with corticosteroids and antihistamines had no significant effect on the effectiveness or safety of RDD in patients with confirmed hypersensitivity to paclitaxel in the study population. Moreover, these premedications can mask early signs of hypersensitivity and delay treatment. We believe that systematic premedication with these drugs for patients undergoing RDD should be carefully and individually assessed if their only purpose is to prevent breakthrough reactions during RDD.

Long Term Efficacy, Safety and PK/PD Profile of the Anti-C1s Antibody (BIVV009) in Primary Cold Agglutinin Disease Patients

Background: Cold agglutinin disease is an autoimmune hemolytic anemia with limited treatment options and no established standard of care. The pathophysiology is driven by the classical complement pathway in which IgM auto-antibodies bind erythrocytes and fix complement via initial binding and activation of the C1 complex generating active C1s protease. Anemia results from extravascular hemolysis of complement opsonized erythrocytes, primarily in the liver. The anti-C1s antibody BIVV009 inhibits C1s activity, and specifically blocks the classical complement pathway, leaving the alternate and lectin complement pathways intact. We hypothesized that classical complement pathway blockade using BIVV009 would prevent hemolysis, correct anemia, and obviate the need for transfusions in patients with primary cold agglutinin disease.Methods: Six patients primary cold agglutinin disease patients were enrolled in an open label Ph1/1b trial. The study was conducted in three parts: Part A, single ascending doses in healthy volunteers (HV); Part B, multiple ascending doses in HV; and Part C, multiple doses in patients with four classical complement mediated diseases including cold agglutinin disease. Patients in Part C received a test dose of 10 mg/kg BIVV009, followed by a full dose of 60 mg/kg 1-4 days later, and three additional weekly doses of 60 mg/kg. Biweekly fixed doses of 5.5g were used for maintenance therapy in a subsequent Named Patient Program.Results: All infusions were well tolerated without need for pre-medication, and pharmacokinetic data demonstrated that BIVV009 infusions supported biweekly treatment. BIVV009 concentrations >18µg/mL inhibited the classical pathway of complement activation (as assessed by the Wieslab-CP assay). BIVV009 infusion subsequently raised endogenous C4 levels 3.2-fold (95%CI: 2.4-4.0 fold; p<0.05) demonstrating classical complement inhibition and reduced complement factor consumption. In addition, deposition of C3d on erythrocytes decreased as measured by flow cytometric analysis, consistent with evidence of classical complement pathway inhibition and reduced erythrocyte opsonization. BIVV009 rapidly abrogated extravascular hemolysis, as measured by normalizing bilirubin levels within 24 hours, normalized haptoglobin levels in 4 of 6 patients within one week, and restoring absolute reticulocyte counts to levels appropriate for the degree of anemia. All 6 of 6 primary cold agglutinin disease patients responded with a hemoglobin increase >3.5 g/dL (mean 4.3g/dl; 95%CI: 3.8-4.9 g/dL; individual best response; p<0.05) within 6 weeks; the lower 95% confidence interval for the responder rate was 54%. Hemolysis and anemia recurred when effective drug levels were cleared from the circulation approximately 3-4 weeks after the last dose of BIVV009 for all patients. Re-exposure to BIVV009 in the named patient program recapitulated the efficacy, again in all patients. Maintenance therapy demonstrated persistent responses without related adverse effects or development of clinically relevant neutralizing antibodies, now with up to 18 months of observation. All five transfusion-dependent patients became and remained transfusion-free during treatment.Conclusion: BIVV009 was well tolerated and immediately stopped hemolysis in 6 of 6 severely anemic patients suffering from primary cold agglutinin disease, increasing hemoglobin by a mean of 4.3g/dl and precluding the need for transfusions while on BIVV009. Based on these encouraging results, BIVV009 received FDA Breakthrough Therapy designation and pivotal trials will be initiated to further define BIVV009 safety and efficacy profiles.Figure 1: individual hemoglobin response patterns in primary cold agglutinin disease patients during the initial exposure of 6 weeks [Display omitted] DisclosuresJaeger:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. D'Sa:Janssen Cilag: Consultancy, Honoraria, Other: Education grant, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Patou:Inc., a Bioverativ Inc. Company: Employment. Panicker:Bioverativ, Inc.: Employment, Equity Ownership. Parry:Bioverativ Therapeutics Inc.: Employment. Gilbert:TrueNorth Therapeutics Inc., a Bioverativ Inc. Company: Other: formerly Employment. Jilma:Biomed: Research Funding; Recardio: Research Funding; Emcools: Research Funding; Bayer: Research Funding; Themis: Research Funding; Syntheract: Research Funding; Bioverativ: Research Funding; TrueNorth Therapeutics: Research Funding; JHL: Research Funding; Baxalta: Research Funding; Arsanis: Research Funding; VitaerisBios: Research Funding; TrueNorth Therapeutics Inc.: Consultancy; Valneva: Research Funding; Prediction Biosciences: Research Funding; Boehringer Ingelheim: Research Funding; Octapharma: Research Funding.

External rotation method for reduction of acute anterior dislocation of shoulder

Introductions: Many different techniques of reduction of acute anterior shoulder dislocation have been described. The aim of this study was to evaluate the effectiveness of external rotation method for reduction of acute anterior shoulder dislocation.&#x0D; Methods: Fifty-one patients with acute anterior shoulder dislocations with or without greater tuberosity fracture were reduced during a period from January 2013 to January 2015. The external rotation method was used as an initial reduction method performed by orthopaedic surgeon on call or residents. Data sheets completed by the orthopaedic surgeon on call or residents were evaluated with regard to the type of dislocation, the effectiveness of the procedure in achieving reduction, the need for premedication, the ease of performing the reduction, and complications, if any.&#x0D; Results: There were 42 male and nine female patients between 18 to 78 years. Among 51 patients, 49 had successful reduction. No premedication was required in 33 patients who had a successful reduction, and the average time required for reduction in 23 patients was within two minutes whereas 20 patients reduced within five minutes. Only four patients reported severe pain during the process of reduction. The method was not successful in two patients with subcoracoid dislocation associated with displaced fracture of the greater tuberosity.&#x0D; Conclusions: External rotation method is reliable, safe, simple and relatively painless method for reduction of acute anterior shoulder dislocation.

Abstract P5-16-29: Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: A meta-analysis

Abstract Background: Nanoparticle albumin-bound paclitaxel (nab-Paclitaxel), a novel solvent-free taxane-based regimen, was hypothesized to have enhanced drug transport to tumors, shorter infusion schedules and no need for premedication. The value of nab-Paclitaxel in neoadjuvant systemic therapy (NST) for breast cancer remains uncertain. We performed a meta-analysis to assess efficacy and toxicity of nab-Paclitaxel compared to conventional taxane regimens (paclitaxel, docetaxel) within randomized clinical trials. Methods: A systematic search was performed using the medical subject heading (MeSH) terms ''breast neoplasms'', as well as (1) breast cancer; AND (2) nab-Paclitaxel OR nanoparticle paclitaxel; AND (3) neoadjuvant OR preoperative OR primary systemic in both Pubmed databases and proceedings of oncologic meetings including ASCO, ESMO and SABCS. Pooled rates of pathological complete response(pCR), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model to determine the effect of neoadjuvant nab-paclitaxel. Results: Twenty-one studies with 2357 patients were included, 3 of which (GeparSepto[1], ETNA[2], Showa trial[3]) were randomized clinical trials. The aggregate pCR rate (ypT0/is ypN0) was 32% (95% CI 25-38%) in unselected breast cancer patients and was 14%(95% CI 11-17%), 41%(95% CI 38-45%), 54%(95% CI 43-66%) in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), triple negative breast cancer(TNBC), HER2+ patients, respectively. Within the HER2+ population, pCR rate was 61%(95% CI 47-74%) for HR- and 40%(95% CI 28-52%) for HR+ tumors. Regarding randomized clinical trials, the probability of achieving pCR was significantly higher in the nab-paclitaxel group than in the conventional taxanes group (OR=1.383, 95%CI 1.141-1.676, p=0.001). A funnel plot of the effect size for each randomized trial against the precision showed no asymmetry, which indicating no potential publication bias. In the safety analysis (GeparSepto[1], ETNA[2]), hematological toxic effects were generally equivalent in nab-paclitaxel and paclitaxel group. For non-hematological toxic effects, all grades and grade≥ 3 peripheral sensory neuropathy occurred more frequently with nab-paclitaxel compared to paclitaxel (all grades, OR=2.090, 95%CI 1.016-4.302, p=0.045; grade≥ 3, OR=3.766, 95%CI 2.324-6.100, p&amp;lt;0.001). Hypersensitivity was more common with paclitaxel than nab-paclitaxel at any grade and grade≥ 3. Other non-hematological toxic effects did not significantly differ between two groups. Conclusion: nab-Paclitaxel is an effective antitumor drug in NST of breast cancer, especially for TNBC and HER2+ tumors, in terms of pCR. Exchange of nab-Paclitaxel for conventional taxanes could significantly improve pCR rate with reasonable toxicities. Clinical trial information: 1.Lancet Oncol.2016,17:345-56.; 2.J Clin Oncol.2016,34(suppl; abstract 502).; 3.J Clin Oncol.2015,33(suppl; abstract 136). Citation Format: Zong Y, Wu J, Shen K. Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-29.

Альбуминсвязанный паклитаксел в терапии метастатического рака молочной железы

Metastatic breast cancer (mBC) continues to be an incurable disease, but modern drug therapy, associated with the steady extension of the arsenal of active cytostatic drugs and the development of new treatment options, provides the long-term control of tumor growth, transforming into chronic pathology. Nab-paclitaxel (nanodispersed albumin-bound paclitaxel) is one of such options. This innovative dosage form provides the active transport of the drug through the vascular endothelium with the creation of the high concentration in the tumor tissue. Clinical trial of nab-paclitaxel compared with traditional taxanes (paclitaxel and docetaxel) have demonstrated high efficiency of a new drug both in the general population and in the selected subgroups of patients, including treated with anthracyclines, patients with invasive disease, damages of the visceral organs, younger patients and others. Nab-paclitaxel proved to act in patients treated with taxanes, the physician can use this drug one again and thus we have another line of therapy. Nab-paclitaxel can be effectively and safely combined with trastuzumab in patients with mBC associated with HER2+. In addition, the drug because of the unique formula does not cause hypersensitivity reactions and differs from traditional taxanes of the variant of application. No need for premedication with dexamethasone let us appoint the drug in patients with comorbid conditions: severe arterial hypertension, diabetes, gastric and duodenal ulcers and others. High safety of nab-paclitaxel was approved in elderly patients as well.

S63 - Treatment of Kaposi's Sarcoma (KS) with nab-paclitaxel

Background: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm that may represent a difficult therapeutic challenge in disseminated stages. Liposomal anthracyclines, or combination chemotherapy are widely used to treat this kind of patients. The efficacy of taxanes (paclitaxel and docetaxel), as agents with antiangiogenic properties, has been described previously in the treatment of KS patients butthe length of the infusion, the need for pre-medication with steroids and toxicity caused by solvents - Cremophor EL (CrEL) and polysorbate 80 (Tween80) - can limit their utilization, especially in elderly patients.Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication which can make it easier to tolerate. At the moment there are no studies on its efficacy and safety in older KS patients. Methods: After written informed consent was obtained a phase II trial was conducted with nab-paclitaxel in 6 patients with advanced-stage KS to assess its safety and antitumor activity. The mean age of patients was 74,8 years( range 71-83). Nab-paclitaxel was administered at a fixed dose of 100 mg intravenously over 30 minutes administered weekly on days 1, 8, and 15 of each 4-week cycle for 4 cycles. No premedication to prevent hypersensitivity reactions was required before administration. Thereafter, if the patient experienced stable disease or better response, treatment doses were given every two weeks until complete disease remission, disease progression, or unacceptable toxicity occurred. Results: All patients improved dramatically after chemotherapy. Partial desinfiltration (n = 2) or complete desinfiltration (n = 4) of all papulonodular skin lesions was observed with marked improvement of lymphedema in 1 patient. Grade 3 neutropenia and thrombocytopenia were observed in three of six and one of six patients, respectively. It was not observed any grade 4 toxicity Conclusions: Classic KS predominantly affects elderly people over 60 years, many of whom do not tolerate aggressive chemotherapy regimens well due to frequent comorbidity and diminished cardiovascular and bone marrow reserves. Nab-paclitaxel has a good and rapid efficacy in our experience which involved a setting of patients difficult to manage.

Weekly nab-paclitaxel in elderly patients with classic Kaposi sarcoma.

e22539Background: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm that may represent a difficult therapeutic challenge in disseminated stages. Liposomal anthracyclines, or combination chemotherapy are widely used to treat this kind of patients.. The efficacy of taxanes (paclitaxel and docetaxel), as agents with antiangiogenic properties,has been described previously in the treatment of KS patients but the length of the infusion, the need for pre-medication with steroids and toxicity caused by solvents can limit their utilization , especially in elderly patients. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication which can make it easier to tolerate .At the moment there are no studies on its efficacy and safety in older KS patients . Methods: After written informed consent was obtained a phase II trial was conducted with nab-paclitaxel in 6 patients with advanced-stage KS to assess its safety and antitumor activity. The mean ...

Identification of novel peptide biomarkers to predict safety and efficacy of cow's milk oral immunotherapy by peptide microarray.

Cow's milk oral immunotherapy (CM-OIT) is still an experimental treatment. The development of novel biomarkers to predict the safety and efficacy of CM-OIT is crucial to translate this treatment to common clinical practice. To analyse long-term changes in IgE and IgG4 epitope binding profile induced by CM-OIT to identify safety and efficacy biomarkers. We studied 25 CM-allergic children who underwent CM-OIT and seven non-treated CM-allergic children as controls. CM-OIT patients were classified as low, moderate, and high risk according to the number of allergic reactions (safety), time required to achieve desensitization (efficacy) and need of premedication. IgE and IgG4 peptide microarray immunoassay was performed using a library of overlapping peptides of CM proteins at baseline, after oral desensitization, and 6, 12, and 24months of follow-up. Cow's milk oral immunotherapy induced a rapid increase of IgG4-binding epitopes and a slow decrease in IgE-binding epitopes. High-risk patients recognized a statistically significant higher number of IgE peptides in caseins at all the times studied. Similar but less pronounced changes were observed for IgG4-positive peptides. Clustering analysis grouped together the high-risk patients, and we identified 13 regions of caseins significantly differed between groups of patients. Bioinformatics analysis selected two sets of 16 IgE-binding peptides at baseline that predicted safety (R(2) =0.858) and efficacy (R(2) =0.732), respectively, of CM-OIT. We found two sets of IgE-binding peptides that can be used as novel biomarkers to predict the safety and efficacy of CM-OIT before starting treatment.

Comparison of Transesophageal Echocardiography Versus Computed Tomography for Detection of Left Atrial Appendage Filling Defect (Thrombus)

Patients with atrial fibrillation, who are referred for radiofrequency pulmonary vein antral isolation, frequently undergo transesophageal echocardiography (TEE) to detect and/or exclude left atrial or left atrial appendage (LAA) thrombus and cardiac computed tomographic angiography (CCTA) to define and/or evaluate left atrial and pulmonary venous anatomy. Previous studies have reported CCTA to have high sensitivity and negative predictive value (NPV) for detecting thrombus in the LAA. Previous studies determining an optimal LAA/ascending aorta (AA) Hounsfield unit (HU) density ratio for detection of LAA thrombus have been small, with limited numbers of thrombi. We thus sought to determine both the optimal cutoff for LAA HU density and LAA/AA HU density ratio in detecting LAA thrombus compared with TEE in a multicenter population. We included 84 patients who had undergone CCTA and TEE. LAA was evaluated by 64-row CCTA qualitatively (visual filling defect) and quantitatively (measurement of LAA HU density and LAA/AA HU density ratio), using a 1-cm area of interest in the same axial plane. Results were compared with TEE visualization of thrombus or spontaneous echo contrast. Qualitative identification of thrombus in LAA by CCTA compared with TEE detection of thrombus had a sensitivity of 100%, a specificity of 77.9%, a positive predictive value (PPV) of 51.6%, an NPV of 100%, and a total accuracy of 82.1%. The optimal LAA HU density cutoff for thrombus detection was 119 with a sensitivity of 88%, a specificity of 86%, PPV 56%, and an area under the curve of 0.923 (p = 0.0004). The optimal LAA/aorta HU ratio was 0.242 with a sensitivity of 87%, a specificity of 88%, a PPV of 64%, and an area under the curve of 0.921 (p = 0.0011). There is no significant difference (p = 0.72) between both areas under the curve, and both measurements improved the specificity and PPV compared with qualitative measures. Multidetector computed tomography is an imaging technique that can exclude LAA thrombus with very high NPV. Quantitative measurement of LAA HU density (cutoff 119) or LAA/aorta HU density ratio (cutoff 0.242) improves accuracy of positively detecting LAA thrombus. This technique is especially useful when delayed scanning is not performed and LAA is found incidentally after the patient scanning is complete.

A simple, safe and painless method for acute anterior glenohumeral joint dislocations: “the forward elevation maneuver”

The glenohumeral joint is the most frequently dislocated joint in the body. Numerous techniques for reducing an acute anterior dislocation of the glenohumeral joint have been described. The goal of this study was to assess the efficacy of Janecki's forward elevation maneuver for reducing a traumatic acute anterior glenohumeral joint dislocation. Between May 2010 and November 2011, the forward elevation maneuver was applied to 27 patients who presented to the emergency department of Yuzuncu Yil University Medical School with a traumatic anterior glenohumeral joint dislocation. For each patient, the forward elevation maneuver was used to reduce the anterior glenohumeral joint dislocation. The type of dislocation, the effectiveness of the procedure in achieving reduction, the need for premedication, the ease of performing the reduction and complications (if present) were noted. Janecki's forward elevation maneuver was successful for 25 patients (92.6 %) on the first attempt. Premedication was not used for 22 patients, and reduction was successful for 20 of them. The method was not successful in two cases. Twenty-three of the patients (85.2 %) experienced no pain or mild pain. Complications referred to the reduction technique were not found in any patient. This paper concludes that Janecki's forward elevation maneuver is a simple, safe, painless, and effective reduction method. Consequently, the forward elevation maneuver seems to be a good method for reducing anterior glenohumeral joint dislocation.

An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) versus conventional paclitaxel for metastatic breast cancer patients: the COSTANza study

PurposePaclitaxel albumin (nab-paclitaxel) is a nanoparticle albumin-bound paclitaxel formulation aimed at increasing therapeutic index in metastatic breast cancer. When compared to conventional paclitaxel, nab-paclitaxel has a reported longer time to progression, higher response, lower incidence of neutropenia, no need for premedication, shorter time of administration, and in pretreated metastatic breast cancer patients, extended overall survival. This study investigates the cost-effectiveness of nab-paclitaxel versus conventional paclitaxel for pretreated metastatic breast cancer patients in Italy.Materials and methodsA Markov model with progression-free, progressed, and dead states was developed to estimate costs, outcomes, and quality adjusted life years over 5 years from the Italian National Health Service viewpoint. Patients were assumed to receive nab-paclitaxel 260 mg/m2 three times weekly or conventional paclitaxel 175 mg/m2 three times weekly. Data on health care resource consumption was collected from a convenience sample of five Italian centers. Resources were valued at Euro (€) 2011. Published utility weights were applied to health states to estimate the impact of response, disease progression, and adverse events on quality adjusted life years. Three sensitivity analyses tested the robustness of the base case incremental cost-effectiveness ratio (ICER).Results and conclusionCompared to conventional paclitaxel, nab-paclitaxel gains an extra 0.165 quality adjusted life years (0.265 life years saved) and incurs additional costs of €2506 per patient treated. This translates to an ICER of €15,189 (95% confidence interval: €11,891–€28,415). One-way sensitivity analysis underscores that ICER for nab-paclitaxel remains stable despite varying taxanes cost. Threshold analysis shows that ICER for nab-paclitaxel exceeds €40,000 only if cost per mg of conventional paclitaxel is set to zero. Probabilistic sensitivity analysis highlights that nab-paclitaxel has a 0.99 probability to be cost-effective for a threshold value of €40,000 and is the optimal alternative from a threshold value of €16,316 onwards. Based on these findings, nab-paclitaxel can be considered highly cost-effective when compared to the acceptability range for ICER proposed by the Italian Health Economics Association (€25,000–€40,000).

CPC-012 An Italian Cost-Effectiveness Analysis of Paclitaxel Albumin (Nab-Paclitaxel) Vs. Conventional Paclitaxel For Metastatic Breast Cancer Patients: The COSTANZA Study

BackgroundPaclitaxel albumin (nab-paclitaxel) is a nanoparticle albumin-bound paclitaxel formulated with the aim of increasing the therapeutic index in metastatic breast cancer (MBC). When compared to conventional paclitaxel, nab-paclitaxel has reported...

The Role of Paclitaxel Albumin-Stabilized Nanoparticle Formulation (Nab-Paclitaxel) in the Treatment of Breast Cancer: A Short Review

The efficacy of conventional cytotoxic drugs has reached a plateau in breast cancer therapeutics. Targeted and tumor-directed therapies are required to improve the outcome and reduce toxicity. Â Â Â Â Â Â Â Â Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel solvent-free formulation of paclitaxel. It demonstrates several practical advantages over paclitaxel, including a shorter infusion time, no need for premedication and endogenous albumin transport to concentrate paclitaxel within the tumor cells. A pivotal phase III study demonstrated superior efficacy and less toxicity of nab-paclitaxel in comparison to the traditional solvent containing paclitaxel as second-line therapy for metastatic breast cancer patients. Furthermore, in a randomized phase II study, nab-paclitaxel has shown clinical benefit versus docetaxel as first-line treatment in metastatic breast cancer and based on the results of this trial recently gained approval as single-agent therapy in this setting. In addition, many small phase II studies have shown that nab-paclitaxel is effective in the adjuvant and neo-adjuvant setting when combined with other cytotoxic or biological agents. These data are summarized in this short review providing evidence that nab-paclitaxel is an active treatment option with favorable toxicity profile for women with breast cancer.