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      Desensitization in patients with hypersensitivity to platinum and taxane in gynecological cancers

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          Abstract

          Background

          Exposure to paclitaxel and carboplatin has the risk of developing hypersensitivity reactions (HSRs), which could necessitate using less effective treatments to avoid anaphylaxis. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen; therefore, this study investigated rates and benefits of successful desensitization in patients with gynecologic cancers (GC).

          Methods

          We collected data from 241 patients with GC who had at least one cycle of platinum or taxane chemotherapy. The rate of HSRs and successful desensitization were evaluated, and an outcome analysis was conducted.

          Results

          The rate of HSRs to platinum and taxane was 6.39% and 13.07%, respectively. We observed a 100% success rate of desensitization in our cohort. Patients with HSR were significantly younger (57.1 vs. 64.9 years, p = 0.030) in the taxane cohort. Importantly, the overall survival (OS) of patients with platinum and taxane HSRs who underwent desensitization was comparable to that of patients with no HSRs (platinum vs. controls; median OS 60.36 vs. 60.39 months, p = 0.31; taxane vs. controls; OS 80.29 vs. 60.00 months, p = 0.59).

          Conclusion

          Thus, we show that desensitization for platinum and taxane HSRs is safe and effective, resulting in an outcome that is well comparable to patients without HSR. Based on these observations, desensitization procedures might be considered as standard of care before switching to less effective treatment for patients with GC.

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          Most cited references35

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          Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.

          In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Eligible patients had measurable/assessable OC that had progressed two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
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            Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

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              Hypersensitivity reactions from taxol.

              Taxol is an antitumor agent in clinical trial that has been shown to have activity against advanced ovarian carcinoma and melanoma. Hypersensitivity reactions (HSRs) have been one of the toxicities observed with administration of this drug. Of 301 patients treated, 32 patients have had definite (27 patients) or possible (five patients) hypersensitivity reactions to taxol. All but one patient had the reaction from the first or second exposure to this agent. Reactions occurred at a variety of doses and were characterized most frequently by dyspnea, hypotension, bronchospasm, urticaria, and erythematous rashes. Thirteen (41%) patients had received premedication designed to prevent such toxicity; nevertheless, they sustained HSRs. Prolonging the drug infusion appears to have somewhat reduced, but not obviated, the risk of HSRs. The cause (taxol itself or its excipient Cremophor EL; Badische Anilin und Soda-Fabrik AG [BASF], Ludwigshafen, Federal Republic of Germany) and the mechanism of these reactions to taxol are unknown. We provide guidelines to prevent or minimize such toxicity and treat reactions if they still occur.
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                Author and article information

                Contributors
                celine.montavon@usb.ch
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                22 December 2023
                January 2024
                : 13
                : 1 ( doiID: 10.1002/cam4.v13.1 )
                : e6840
                Affiliations
                [ 1 ] Department of Gynecology and Gynecological Oncology, Hospital for Women University Hospital Basel Basel Switzerland
                [ 2 ] Gynecological Cancer Center University Hospital Basel Basel Switzerland
                [ 3 ] Peter MacCallum Cancer Center East Melbourne Victoria Australia
                [ 4 ] Division of Allergy Unit, Department of Dermatology Cantonal Hospital Aarau Aarau Switzerland
                [ 5 ] Department of Dermatology University Hospital Basel Basel Switzerland
                [ 6 ] Cancer Center, Cantonal Hospital Baselland Medical University Clinic Liestal Switzerland
                Author notes
                [*] [* ] Correspondence

                Céline Montavon, Gynecological Cancer Center, Hospital for Women, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.

                Email: celine.montavon@ 123456usb.ch

                Author information
                https://orcid.org/0000-0002-1574-6572
                https://orcid.org/0000-0002-5235-2556
                https://orcid.org/0000-0002-4069-6976
                https://orcid.org/0000-0002-4056-3225
                https://orcid.org/0000-0002-4595-8226
                https://orcid.org/0009-0004-1003-1078
                https://orcid.org/0000-0002-4186-445X
                Article
                CAM46840 CAM4-2023-08-4062.R1
                10.1002/cam4.6840
                10807606
                38140783
                da75fcb2-9e4f-467e-aa69-8f60731a0508
                © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 October 2023
                : 20 August 2023
                : 27 November 2023
                Page count
                Figures: 3, Tables: 3, Pages: 12, Words: 5152
                Funding
                Funded by: Gottfried und Julia Bangerter‐Rhyner‐Stiftung
                Award ID: 0297
                Funded by: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung , doi 10.13039/501100001711;
                Award ID: P500PM_20726
                Funded by: Freie Gesellschaft Basel
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                January 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.6 mode:remove_FC converted:24.01.2024

                Oncology & Radiotherapy
                chemotherapy,desensitization,gynecologic cancer,hypersensitivity reaction,platinum,taxane

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