Risk Of Hypersensitivity Reactions Research Articles

Hypersensitivities to sesame and other common edible seeds.

Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1-0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross-reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto-injectors. We did not encounter any well-designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future.

Low rate of cetuximab hypersensitivity reactions in Northeast Tennessee: An Appalachian effect?

Cetuximab is a monoclonal antibody with a known risk of hypersensitivity reactions. Early studies showed hypersensitivity reaction rates of 3%, but there appears to be a higher incidence in the southeastern United States. To confirm the findings from nearby institutions that cetuximab-associated hypersensitivity reactions occur in approximately 20% of patients in the southeastern United States. A retrospective chart review was conducted at Johnson City Medical Center in Johnson City, Tennessee. Each patient's first infusion was analyzed for hypersensitivity reaction, as well as for demographic information such as allergy and smoking history, pre-medications, and malignancy type. Data from the first infusion of cetuximab were collected for a total of 71 patients with various malignancies. The overall rate of grade 3 or higher hypersensitivity reaction was 1.4%, and total rate of hypersensitivity reaction was 8.5%. These findings more closely correlate to the early clinical trials and package insert. Both severe (p = 0.001) and any-grade (p = 0.002) hypersensitivity reaction occurred less frequently in one Southeastern Appalachian medical center compared to academic medical centers directly to the east and west. Patients in southern Appalachia may be less likely to develop cetuximab hypersensitivity reactions compared to surrounding areas in the Southeastern U.S. These results lend support to the theory that exposure to lonestar ticks (Amblyomma americanum) may be responsible for the development of IgE antibodies to cetuximab that cause hypersensitivity reactions. The development of quick and reliable bedside predictors of cetuximab hypersensitivity reactions may aid clinicians considering the use of cetuximab.

A novel risk score for prediction of hypersensitivity reactions in cancer patients receiving carboplatin: Retrospective observational analysis.

e282 Background: Hypersentitivity reactions (HSRs) from carboplatin are high incidence and most severity in Chulabhorn hospital. These reactions are associated with several causes including patient factors and experience in drug used. A reliable and valid tool for evaluated risk of HSRs before started carboplatin infusion should lead to prevent or decrease severity of the reactions. We innovated risk score to screen patient at high risk of HSRs. Methods: From October 2013 to September 2014, all cancer patients who received carboplatin in Chulabhorn hospital were included. A retrospective study design to developed risk scoring system for prediction of patients at high risk of carboplatin hypersensitivity called “Hypersensitivity risk score”. The hypersensitivity risk score was calculated for all patients receiving carboplatin and data for carboplatin hypersensitivity were obtained from medical records. Expected and observed HSRs were analyzed by using receiver operating characteristic (ROC) curve. Results: Seventy-three cancer patients received carboplatin and five (7%) patients had HSRs. Our scoring algorithm based on cancer type, number of carboplatin retreatment, duration between each retreatment, and number of carboplatin infusions prior to first reaction. All significant predictors were weighted into points and categorized to risk group which ranged from 0 to 8 . The ROC analysis for hypersensitivity risk score indicated good predictive accuracy with an area under the curve of 0.96 (95 %CI: 0.91-1.00). Data showed high sensitivity (80%) and specificity (94.85%) for a risk score cut-off of 4. The hypersensitivity risk score clearly differentiated the low (0-1), intermediate (2-3) and intermediate-high (4-5) and high (6-8) risk patients. Conclusions: The hypersensitivity risk score is a simple scoring system with high predictive value and differentiates low versus high risk patients. This score should be used for screen high risk of hypersensitivity reactions in patients receiving carboplatin.

Роль nab-паклитаксела в лечении больных метастатическим раком молочной железы

Nab-paclitaxel is nanoparticle albumin-bound paclitaxel. Nab-paclitaxel is free from any kind of solvent and thus reduces the risk of hypersensitivity reactions and other side effects, compared with standard taxanes (paclitaxel, docetaxel). There is no need to use premedication with glucocorticoids and antihistamines during nab-paclitaxel application. In addition, several studies have demonstrated that nab-paclitaxel allows achieving a higher drug concentration in tumor. The article deals with the basic studies of nab-paclitaxel application using different doses and introduction regimens in patients with metastatic breast cancer. We show the algorithm for optimal use of nab-paclitaxel in different clinical cases.

Carboplatin hypersensitivity reactions (HSR) in carboplatin retreatment for recurrent ovarian cancer.

5572 Background: The reported risk of HSR during carboplatin retreatment is 18-44% and increases with repeated carboplatin exposure. We aimed to prospectively study the effect of an extended increm...

Ferric carboxymaltose: a guide to its use in iron deficiency

Ferric carboxymaltose (Ferinject®, Injectafer®) is an important intravenous iron preparation option for the treatment of iron deficiency. A single high dose [up to 750 mg (USA) or 1000 mg (EU) of iron] can be administered intravenously in a short time frame (15 min). Thus, fewer doses of ferric carboxymaltose may be needed to replenish iron stores relative to some other intravenous iron preparations. Ferric carboxymaltose improved self-reported patient global assessment, New York Heart Association functional class and exercise capacity in patients with chronic heart failure and iron deficiency in the FAIR-HF and CONFIRM-HF trials. In other trials, ferric carboxymaltose replenished iron stores and corrected anaemia in various populations with iron-deficiency anaemia, including patients with chronic kidney disease, inflammatory bowel disease or heavy uterine bleeding, postpartum iron-deficiency anaemia and perioperative anaemia. Intravenous ferric carboxymaltose was generally well tolerated, with a very low risk of hypersensitivity reactions. In general, it was better tolerated than oral ferrous sulfate, mainly reflecting a lower incidence of gastrointestinal adverse effects. The higher acquisition cost of ferric carboxymaltose was offset by lower costs for other items, with the potential for cost savings.

A validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: The AVOID trial.

727 Background: Patients treated with oxaliplatin are at risk for hypersensitivity reactions. The incidence of hypersensitivity reactions in clinical practice is estimated to be 12% to 20%. Prescribing information says that oxaliplatin is incompatible in solution with alkaline medications or media and must not be mixed these or administered simultaneously through the same infusion line. Because steroid is alkaline, the coinfusion of steroids and oxaliplatin can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of steroid in this therapy is unknown. Therefore, dexamethasone is routinely given to patients before they receive chemotherapy. However, we have reported that the pH after the addition of DEX (6.6 mg) to oxaliplatin was less than 7.4, and there is possibility that hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of dexamethasone (DEX) (Yoshida et al.2012 ASCO-GI) but just in a retrospective study. This prospective study was undertaken to evaluate the effectiveness of coinfusion of DEX to oxaliplatin for controlling hypersensitivity reactions caused by oxaliplatin. Methods: The AVOID trial is a prospective, multicenter, open-label, single-arm, phase II trial investigating hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of DEX. The study included 73 patients who received XELOX or XELOX +bevacizumab therapy for colorectal cancer. In all the patients, oxaliplatin (130mg/m²) was administered in combination with DEX (6.6 mg). Results: Hypersensitivity reactions developed in 3 patients (4.1%). Respiratory symptoms, ocular symptoms and anaphylaxis were not observed in 73 patients. The three patients experienced cutaneous reaction (erythema: grade1). Grade 3 or higher hemotoxicity was noted in 13.7% of the patients, and grade 3 or higher nonhematological toxicity was noted in 13.7%. The response rate was 58.1%. Conclusions: This trial supports coinfusion of dexamethasone and oxaliplatin reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive oxaliplatin, allowing treatment to be completed as planned. Clinical trial information: UMIN000009742.

Characterization of Anaphylaxis After Ecallantide Treatment of Hereditary Angioedema Attacks

Ecallantide is a human plasma kallikrein inhibitor indicated for treatment of acute attacks of hereditary angioedema for patients 12 years of age and older. Ecallantide is produced in Pichia pastoris yeast cells by recombinant DNA technology. Use of ecallantide has been associated with a risk of hypersensitivity reactions, including anaphylaxis. The objective of this detailed retrospective data review was to characterize anaphylaxis cases within the ecallantide clinical trials database. Potential cases of hypersensitivity reactions in the ecallantide clinical development program were identified by examining reported adverse events. The National Institute of Allergy and Infectious Disease criteria were used to identify those events that were consistent with anaphylaxis; these cases were then reviewed in detail. Results from investigational antibody testing also were examined. Among patients who received subcutaneous ecallantide (n= 230 patients; 1045 doses of 30 mg ecallantide), 8 patients (3.5%) had reactions that met the National Institute of Allergy and Infectious Disease criteria for anaphylaxis; none occurred on first exposure to the drug. All 8 reactions had symptom onset within 1 hour of exposure and cutaneous manifestations commonly observed in type I hypersensitivity reactions. All the reactions responded to standard management of type I hypersensitivity reactions and resolved without fatal outcomes. IgE antibody testing to ecallantide or P pastoris was not consistently positive in patients who experienced apparent type I hypersensitivity reactions. Anaphylaxis episodes after subcutaneous ecallantide exposure have clinical features suggestive of type I hypersensitivity reactions. However, anti-ecallantide or anti-P pastoris IgE antibody status was not found to be reliably associated with anaphylaxis.

371P - A Multicenter Phase Ii Trial of Nab-Paclitaxel in Combination with Capecitabine in Patients (Pts) with Her-2 Negative and Triple Negative Advanced Breast Cancer (Abc): an Interim Analysis

ABSTRACT Aim: ABC remains a therapeutic challenge in spite of the use of emerging new drugs. Nab-paclitaxel has better efficacy and no risk of hypersensitivity reactions when compared to paclitaxel. We studied the association of nab-paclitaxel and capecitabine in a novel schedule as I line treatment in a population of HER-2 negative and triple-negative ABC. An interim analysis was preplanned at 54 enrolled pts. Methods: Nab-paclitaxel 150 mg/m2 was administered day 1 and 8 out of 21 days in combination with capecitabine at 825 mg/m2 twice daily, day 1-14 out of 21 days as first line therapy for HER2 negative ABC. The primary endpoints of the study are response rate (RR) and progression-free survival (PFS), secondary endpoints are toxicity and overall survival (OS). Results: Sixty five pts were enrolled from 11 centers, 59 pts (90.8%) evaluable for RR and PFS (ITT), 58 pts evaluable (89.2%) for toxicity. Median age was 56 years (34-77), 21 (32.3%) pts had triple-negative ABC, 44 pts (67.7%) hormone receptor positive ABC. Median number of metastatic site was 2 (range 1-5), visceral disease was present in 48 pts (73.9%). Median number of cycles was 6 (range 1-8). CR were 4 (6.8%), PR 31 (52.5%), for an overall RR (ORR) of 59.3%. SD was observed in 15 pts (25.4%), PD in 9 pts (15.3%). In the subpopulation of triple negative ORR was 50%. Median PFS for all pts was 43 weeks (26-48), 25 weeks (11-37) in triple-negative pts. Hematological toxicity Grade 3/4 was seen in 12/3 pts (18.5%/4.6%) (neutropenia G3/4 10/1 pts (15.4%/1.5%) and febrile neutropenia 2 pts (3%), respectively). Non-hematological toxicity grade 3/4 was seen in 11/10 pts (17%/15.4%), particularly neuropathy G3/4 1/0 (1.5%/0%). Conclusions: Significant clinical activity and good tolerability was seen from the combination of nabpaclitaxel and capecitabine in HER-2 negative ABC. The study is ongoing, but data provide a basis to consider this regimen for further evaluation in phase III trials. Disclosure: All authors have declared no conflicts of interest.

OTC acne products: risk of hypersensitivity reactions

OTC acne products: risk of hypersensitivity reactions

Does Tranexamic Acid Reduce Blood Loss in Total Knee Arthroplasty?

The purpose of the study by Aguilera et al.1 was to assess the clinical effectiveness of two commonly used intraoperative techniques that are currently utilized in total knee arthroplasty to reduce blood loss. These were the application of fibrin glue and the intravenous administration of tranexamic acid. Prospective randomized clinical trials such as this one are critical for clinicians who currently care for patients who are undergoing total knee arthroplasty because often the literature is unclear as to which techniques are most efficacious. Currently, many approaches are utilized to reduce blood loss and the need for transfusions in total knee arthroplasties. These techniques include various electrocautery devices, pharmacological agents, as well as intravenous agents. It has been well-documented within the orthopaedic literature that excessive blood loss has been associated with increased hospital stays, increased complications, increased costs, and decreased patient satisfaction. In addition, the use of allogeneic blood transfusion is not without risk for hypersensitivity reactions and infection. With increased pressures from Medicaid and Medicare to improve quality while reducing costs, there is an increased emphasis on the importance of blood loss studies, such as this one, which attempts to provide Level-I data to help address this quite challenging problem in total knee arthroplasty and to help clinicians make more informed care decisions. In the current study, 172 patients were …

Incretin-mimetics associated pancreatitis: evidence from the spontaneous adverse drug reactions reporting in Italy

Objective: New incretin-mimetics increased the treatment options for type 2 diabetes mellitus. Studies on the safety of incretin-based therapy showed a risk of hypersensitivity reactions, acute pancreatitis, renal failure, infection, thyroid and pancreas cancer. We contributed to safety assessment of these new drugs by evaluating the spontaneous adverse drug reactions (ADRs) reporting in Italy.Research and methods: Reports of suspected ADRs associated with incretin-mimetics were selected from the Italian Spontaneous ADR Reporting Database. For a subgroup of cases belonging to the Hospital of Cento (Ferrara), levels of pancreatic enzymes, amylase and lipase, before and after the therapy with the incretin-mimetics were available.Results: As of December 2012, the reports of ADR associated with hypoglycemic drugs (excluding insulin) were 2443, 1169 (47.85%) concerned the incretin-mimetics. A total of 90 reports described pancreatitis (44) and elevated pancreatic enzymes (46). Out of 90 cases, 34 were serious (37%). Data on amylase/lipase values for 10 patients were provided and an analysis of the published literature was performed.Conclusions: Our data from the daily clinical practice add up and confirm the information available on the association between incretin-mimetics and pancreatic damage and suggest caution in the prescribing of these new drugs and a close monitoring of exposed patients.

Abstract 1188: BRCA 1/2 mutation status is correlated with increased hypersensitivity reactions to carboplatin.

Abstract Background: Carboplatin (Cp) has become the standard first-line chemotherapeutic agent for treatment of ovarian cancer (OvCa), and Cp-related hypersensitivity reaction (HSR) has been observed in 5-20% of patients (pts). The several known potential risk factors for HSR include age, # of prior platinum treatments/cycles, and longer duration of platinum-free interval (PFI). The role of BRCA mutation status has not been studied in the context of Cp HSR, although OvCa pts with BRCAmut+ are treated repeatedly with platinum-based chemotherapies. Methods: The medical records of 74 women who enrolled and initiated at least one cycle of Cp on two phase I clinical trials (NCT01237067 and NCT01445418) with Cp and olaparib (AZD2281) were reviewed. Cp was given with olaparib for a maximum of 8 cycles. Clinical characteristics including BRCA mutation status, history of HSR prior to or on study, and outcomes were analyzed. Results: Primary diagnoses of the 74 pts were ovarian (71), fallopian tube (1), and primary peritoneal (2) carcinomas. Pts had a median age of 56 years (27-80) and ECOG 0-1. 50/74 (68%) pts were BRCA mutation carriers (BRCA 1 [38], BRCA 2 [10], BRCA1/2 [1], BRCApro 68% [1]). All pts had received platinum-based therapy prior to enrollment, and the median # of prior platinum regimens and cycles were 2 (1-6) and 12 (2-42), respectively. The median PFI from the last prior platinum treatment to the first Cp infusion on study was 15.3 months (6-82). 15/74 (20%) pts had a documented history of HSR to Cp prior to enrollment and were pre-medicated with methylprednisolone, H1, and H2 blockers before a slow, incremental Cp infusion. 15/74 (20%) pts developed HSR on study (grade 1 [6], grade 2 [5], and grade 3 [4]), 4 of whom had prior history of Cp HSR. Taken together, the incidence of Cp HSR at any point in the pts’ oncologic history, either prior to or on study, was 35.1% (26/74); prior history of Cp HSR was not predictive of HSR on study. Age, median # of prior platinum cycles, and PFI for the 15 pts with HSR on study vs. those with no HSR history were 52 (27-73) vs. 56 (34-73), 12 (6-20) vs. 10 (2-42), and 21.2 (8-53) vs. 15.3 (6-82), respectively, all of which were not statistically significant. 4/15 (27%) pts with HSR on study (including 2/4 pts with prior history) stopped Cp treatment due to repeated HSR despite pre-medications, while 7/15 (47%) pts stopped therapy for other reasons. The remaining 4/15 (27%) pts successfully completed 8 cycles or are continuing therapy per protocol. BRCA mutation was significantly associated with increased risk of HSR (prior to or on study), 46% (23/50), vs. 11% (2/19) for pts with no BRCA mutation (p = 0.010). Conclusions: Cp re-treatment can be successful for OvCa pts despite prior history of HSR. Prior HSR history did not increase the risk of HSR on study. Being a BRCAmut+ carrier was associated with a statistically significantly greater risk of HSR and may serve as a clinical predictive biomarker of Cp hypersensitivity. Citation Format: Dominic H. Moon, John L. Hays, Christina M. Annunziata, Anne M. Noonan, Lori Minasian, Nicole Houston, Elise C. Kohn, Jung-min Lee. BRCA 1/2 mutation status is correlated with increased hypersensitivity reactions to carboplatin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1188. doi:10.1158/1538-7445.AM2013-1188

Effect of coinfusion of dexamethasone to oxaliplatin on hypersensitivity reactions induced by oxaliplatin in patients with colorectal cancer treated with XELOX.

560 Background: Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. The incidence of severe anaphylactic reaction of oxaliplatin is estimated to be 0.5%, whereas the incidence of other hypersensitivity reactions in clinical practice is estimated to be 12% to 20%. We have reported that there is possibility that hypersensitivity reactions to oxaliplatin could have been prevented by co-infusion of dexamethasone (DEX) (Yoshida et al.2012 ASCO-GI, Yoshida et al, Br J Med Med Res 2012) but just in a small cohort. This study was undertaken to evaluate the effectiveness of co-infusion of DEX to oxaliplatin for controlling hypersensitivity reactions caused by the administration of oxaliplatin. Methods: A retrospective study of patients with advanced colorectal cancer who received XELOX was performed. The study included 101 patients who received XELOX or XELOX +bevacizumab therapy for advanced or recurrent colorectal cancer. In all the patients, oxaliplatin (130mg/m²) was administered in combination with DEX (6.6mg) via the peripheral vein. Results: A total of 101 patients were studied. Hypersensitivity reactions developed in 2 patients (1.98%).Respiratory symptoms, ocular symptoms and anaphylaxis were not observed in 101 patients. Two patients experienced cutaneous reaction (erythema). Grade 3 or higher hemotoxicity was noted in 13.9% of the patients, and grade 3 or higher nonhematological toxicity was noted in 17.8% of the patients. The response rate was 55.4%. Conclusions: Co-infusion of dexamethasone to oxaliplatin reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive XELOX, allowing treatment to be completed as planned. We have already started a new phase II trial to confirm the effects of DEX to prevent the hypersensitivity.

Rituximab hypersensitivity reactions (HSR): Predictors of recurrent and severe reactions based on severity of reaction, NHL histologic subtype, and burden of disease.

e18520 Background: Rituximab is an anti-CD20 monoclonal antibody with efficacy in B-cell malignancies. Grade II-IV HSR occur in 5-10% of patients. There are no data to predict which patients are at risk for more severe rituximab HSR as well as no data on eventual successful rituximab administration in this population. Methods: We analyzed all rituximab HSR in patients at Massachusetts General Hospital between 2006-2010. Patients included had documented HSR on the chemotherapy infusion sheet on our electronic medical record or via referral to allergy for desensitization. Control rituximab-treated patients were identified from tumor registry data. ICD3 codes were used to determine the histologic subtypes. Rates of HSR were analyzed by logistic regression and Fisher's exact test. Severity of HSR was based on an established classification system. Results: Immediate HSR occurred in 9% of patients (79/901) treated with rituximab and premedications. A majority of patients with a HSR developed symptoms on their initial infusion (76%); however, 46% of moderate or severe HSR occurred on subsequent infusions. Severity of HSR was directly correlated to the risk of a recurrent reaction where all patients with severe HSRs and 56% of patients with moderate HSRs had a recurrent reaction in contrast to only 36% of patients with mild reactions (p = 0.005). Advanced stage of disease increased the risk of a moderate or severe HSR (HR = 4, p = 0.02). Waldenstrom’s Macroglobulinemia (WM) accounted for 10% of all HSR while representing only 1% of rituximab treated pts (p < .003 adjusting for multiple comparisons) and 70% of these patients had a HSR. All patients with complex HSR who were referred to allergy for desensitization (n=14) were able to complete therapy safely. Conclusions: Severe rituximab HSR commonly occurs after the initial infusion. Severity of the HSR predicted recurrent HSR and an advanced stage of disease predicted more severe reactions. WM had a disproportionately higher risk for HSR. Despite HSR, we found that all patients were able to tolerate the recommended number of infusions without severe adverse events utilizing medical management and/or desensitization.

High-dose dexamethasone plus antihistamine prevents colorectal cancer patients treated with modified FOLFOX6 from hypersensitivity reactions induced by oxaliplatin

Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. We designed a modified premedication regimen to prevent oxaliplatin-related hypersensitivity reactions and assessed if this approach is effective. A retrospective cohort study of patients with advanced colorectal cancer who received modified FOLFOX6 (mFOLFOX6) was performed. Patients received routine premedication with dexamethasone 8 mg and granisetron 3 mg for the first five cycles of mFOLFOX6. From the sixth cycle onward, cohort 1 received the same premedication, and cohort 2 received modified premedication (diphenhydramine 50 mg orally, followed by dexamethasone 20 mg, granisetron 3 mg, and famotidine 20 mg). We compared the incidence of hypersensitivity reactions, duration of treatment, and reasons for treatment withdrawal between the two cohorts. A total of 181 patients were studied (cohort 1, 81; cohort 2, 100). Hypersensitivity reactions developed in 16 patients (20%) in cohort 1 and 7 (7.0%) in cohort 2 (P = 0.0153). The median number of cycles increased from 9 in cohort 1 to 12 in cohort 2. Apart from progressive disease, neurotoxicity was the reason for discontinuing treatment in 20% of the patients in cohort 1, as compared with 53% in cohort 2. Increased doses of dexamethasone and antihistamine significantly reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive FOLFOX, allowing treatment to be completed as planned.

New microtubule-inhibiting anticancer agents

Importance of this field: Microtubule-inhibiting drugs are among the most commonly prescribed agents in the combat against cancer, though the clinical use of these drugs is limited by acquired resistance, risk of hypersensitivity reactions and intolerable toxicity. With progress in our understanding of cytoskeleton structure and its related signaling pathways, a number of new microtubule-inhibiting agents with diversified structures and modes of action haveemerged.What the reader will gain: This review mainly describes new microtubule-targeting anticancer agents that have been discovered (especially over the past 2 years), with emphasis on their diversity of structures and distinct modes ofaction.Areas covered in this review: Data were obtained exclusively from public sources, including journals and scientific meeting abstracts, up to September 2009.Take home message: A number of new agents have been discovered, and some have entered clinical trials. Even though most of these agents stabilize or destabilize tubulin via binding on the recognized tubulin binding sites, a few compounds bind to tubulin on undefined sites or interrupt microtubule in diverse ways. Moreover, some agents target microtubule indirectly such that they alter the post-translational modification of tubulin. Further investigation into their mechanism of action and evaluation of their anticancer efficacy will help to develop novel regimens that are superior to existingapproaches.

8055 The impact of prophylactic prolonged carboplatin infusion on risk of hypersensitivity reactions during carboplatin retreatment in epithelial ovarian cancer

To estimate the cost-effectiveness of trabectedin plus pegylated liposomal doxorubicin (PLD) compared with PLD alone for the treatment of patients with relapsed platinum-sensitive ovarian cancer who are not expected to benefit from retreatment with platinum-based therapies based on the final survival data published in October 2012.A decision-analytic model estimated the cost per quality-adjusted life-year (QALY) gained for trabectedin plus PLD compared with PLD alone from the UK National Health Service and Personal Social Services perspective over a lifetime horizon. Mean progression-free survival and overall survival were calculated by using parametric survival distributions adjusted for imbalances discovered in the final survival data. Between-arm imbalances included the platinum-free interval, cancer antigen 125 (CA-125), and Eastern Cooperative Oncology Group performance score. Cost categories included drug, administration, medical management, and treatment of adverse events. Quality of life was measured by using the EuroQol five-dimensional questionnaire. Uncertainty was addressed by deterministic and probabilistic sensitivity analysis.Over a lifetime horizon, trabectedin plus PLD increased mean progression-free survival by 3.0 months and overall survival by 9.7 months compared with PLD alone. The additional cost and QALYs of trabectedin plus PLD were £18,476 and 0.49, resulting in an incremental cost-effectiveness ratio of £38,026 per QALY. Sensitivity analyses showed that results were sensitive to platinum-free interval adjustment and the choice of survival distributions.The analysis estimated a significant improvement in mean overall survival and incremental cost per QALY compared with that calculated in the original National Institute for Health and Clinical Excellence assessment, which was based on immature survival data.

Versorgungsnetzwerke für innovative Immuntherapien

Monoclonal antibodies have extended the therapeutic options in the treatment of patients with multiple sclerosis. Further approvals of innovative immune therapies are expected in the near future. Due to the increasing numbers of cases of PML in natalizumab patients and the risk of hypersensitivity reactions as well as the high therapy costs, there is not only a need to define standards regarding organisational and process quality in treating centres, but also to create standards that direct the cooperation between the centres. On the initiative of the German MS Society (DMSG) and the Neurologists Associations, the following proposal is being presented concerning the creation of networks for medical care with innovative immune therapies. These networks have the purpose to help patients obtain access to novel therapies and ensure at the same time the best possible safety.

Hypersensitivity reaction to ranitidine: Description of a case and review of the literature

Ranitidine is an H2-receptor antagonist which is usually well tolerated. Hypersensitivity reactions to ranitidine, as well as other H2 antihistamines, have been rarely described. We report the case of a 47-year-old woman who developed an anaphylactic reaction to ranitidine used as intravenous premedication before anesthesia induction. The patient’s history revealed that previous use of oral ranitidine for a peptic ulcer disease did not cause any adverse reaction. Intradermal test with ranitidine at a dilution of 1:100 gave an intense positive reaction. The protective role of H2-receptor antagonists as premedication is still unclear and should be carefully reconsidered on the basis of the available controversial evidence and the possible risk of hypersensitivity reactions.