Filip AB, Mahmood L, Tilly C, Foster HR, Jackson F, et al.
Annals of emergency medicine •
North American pit viper antivenoms, CroFab® and ANAVIP®, contain galactose-α-1,3-galactose (α-GAL) oligosaccharide. We compared adverse drug reactions, including presumed anaphylaxis, following administration of these antivenoms and investigated biological plausibility of these antivenoms leading to anaphylaxis in α-GAL-immunoglobulin (Ig) E-sensitized individuals. We performed 2 studies. A retrospective chart review from the Arkansas Poison Center (May 2021 to July 2023) identified adverse drug reactions and presumed anaphylaxis in patients treated with crotaline antivenom. Two allergists (JK, LM), blinded to the antivenom used, adjudicated presumed anaphylaxis cases. To assess whether antivenoms could activate basophils from α-GAL-IgE-sensitized individuals, basophil activation tests were performed on blood from 5 α-GAL-IgE-sensitized participants with a history of mammalian meat allergy. Basophil activation was assessed by %CD63 upregulation. Adverse drug reactions without presumed anaphylaxis occurred in 7 out of 171 (4.1%) Fab recipients versus 8 out of 37 (21.6%) F(ab') recipients (Δ=17.5%, 95% confidence interval [CI] [4.0 to 31.0]). Presumed anaphylaxis was observed in 3 out of 171 (1.8%) for Fab and 6/37 (16.2%) for F(ab') (Δ=14.3%, 95% CI 2.5 to 26.2). In the basophil activation tests, the mean EC for basophil CD63 activation was 144-fold higher for Fab (mean, [standard deviation]; 647 μg/mL of antivenom [627]) compared to F(ab') (4.48 μg/mL of antivenom [2.75]). We demonstrate a substantial incidence of adverse drug reactions and presumed anaphylaxis to crotaline antivenoms in an α-GAL endemic region, with F(ab') antivenom associated with more reactions than F(ab). Clinicians in α-GAL endemic regions should be cautious in the use of antivenoms, especially for patients with α-GAL allergy.
A 17-year-old female with cystic fibrosis was diagnosed with alpha-gal syndrome after 6 months of progressively worsening abdominal pain. Alpha-gal is an acquired allergy to mammalian products that can impact what individuals are able to consume. This syndrome may impact an individual's ability to take medications that are animal derived or contain animal derived excipients. Through dietary removal of mammalian products, she was able to see a reduction in gastrointestinal symptoms. With the success of dietary modifications and modification of her allergy medication formulation, maintenance medication changes did not need to be made. This allowed her to continue her pre-established medication treatment plan (including exogenous pancreatic enzymes). This case highlights potential complexities in medication management of alpha-gal syndrome in an adolescent with cystic fibrosis.
Farley J, Sill MW, Birrer M, Walker J, Schilder RJ, et al.
Gynecologic oncology •
The purpose of this study was to evaluate the safety and efficacy of cetuximab (C225), an antibody that inhibits epidermal growth factor receptor (EGFR) activity, with cisplatin and to explore associations between EGFR protein expression with patient demographics or clinical outcome. Women with advanced, persistent, or recurrent carcinoma of the cervix were eligible. The women received cisplatin at 30mg/m(2) on days 1 and 8 with a loading dose of cetuximab at 400mg/m(2) followed by 250mg/m(2) on days 1, 8, and 15 in a 21day cycle. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior chemotherapy (CT). EGFR protein expression in pre-treatment tumor was analyzed by immunohistochemistry. Between September 2004 and March 2008, 76 patients were enrolled. Of these, 69 were eligible and evaluable; 44 (64%) received prior chemotherapy. There were 4 responses in each group, prior chemotherapy and no chemotherapy, 9% and 16%, respectively. Grade 4 toxicities included anemia (1), allergy (1), metabolic (1), and vascular (1). The most common grade 3 toxicities were metabolic (15), dermatologic (8), fatigue (6), and gastrointestinal (6). EGFR protein was expressed in 47/48 (98%) of tumors analyzed with a median cellular expression of 81%. Exploratory analyses revealed a trend between the percentage of cells expressing EGFR protein and PFS (hazard ratio=1.76, 95% confidence interval=0.96-3.21). The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy.
This phase II trial assessed the activity and tolerability of cetuximab (C225, Erbitux) in combination with carboplatin in patients with relapsed platinum-sensitive ovarian or primary peritoneal carcinoma. Patients were to receive combination therapy with cetuximab (initial dose of 400 mg/m2 intravenously on cycle 1, day 1, followed by weekly infusions of 250 mg/m2) and carboplatin (AUC of 6 on day 1 and every 3 weeks). The primary objectives of this trial were to estimate the anti-tumor activity and adverse events of this combination therapy. Immunohistochemical expression of EGFR was evaluated in tumor specimens from patients enrolled in this trial. Of the 29 patients, 28 (97%) were eligible and evaluable for analysis of the efficacy and toxicity of cetuximab administered in combination with carboplatin. Of the evaluable entries, 26 had EGFR-positive tumors and the response rate in this group of patients was as follows: 9 demonstrated an objective response (3 CR; 6 PR) and 8 had stable disease. The response rate did not meet criteria for opening a second stage of accrual. The median time to progression was 9.4+ months (range: .9-22.2+). The most commonly observed adverse events were dermatologic toxicity (grade 3 in 32%), thrombocytopenia (grade 3 in 14%), and hypersensitivity reactions (grade 3 and 4 in 18%). Cetuximab administered in combination with carboplatin had modest activity in screened patients with EGFR-positive, relapsed platinum-sensitive ovarian or primary peritoneal carcinoma. Cetuximab was associated with an acneiform rash in a majority of patients and occasional serious hypersensitivity reactions.
