Novel Desensitization Protocol Utilizing Conventional Formulations to Mitigate Temozolomide-Related Skin Hypersensitivity

Novel Desensitization Protocol Utilizing Conventional Formulations to Mitigate Temozolomide-Related Skin Hypersensitivity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Novel Desensitization Protocol Utilizing Conventional Formulations to Mitigate Temozolomide-Related Skin Hypersensitivity Morgan Cantley, Clyde Coleman, Rachael M. Morgan, Niharika Reddy, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6334053/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jun, 2025 Read the published version in Cancer Chemotherapy and Pharmacology → Version 1 posted 9 You are reading this latest preprint version Abstract Temozolomide (TMZ) is an oral alkylating agent used in the first-line treatment regimen for glioblastoma (GBM). Multiple documented cases of dose-limiting TMZ rash utilize desensitization protocols requiring complex TMZ dosing and dilutions. We report a TMZ-related skin hypersensitivity managed by a desensitization protocol utilizing only commercially available dosage forms of TMZ. This protocol allowed the patient to continue optimal treatment for GBM without the need for complicated compounding and dilution efforts. Glioblastoma temozolomide desensitization rash drug-induced reactions Figures Figure 1 Introduction Temozolomide (TMZ) is an oral alkylating agent with antitumor activity across various malignancies, including glioblastomas, newly diagnosed and refractory anaplastic astrocytoma. 1 TMZ can also be used in progression of neuroendocrine tumors of the gastrointestinal tract. 2 It is most widely used for GBM as when administered concurrently with radiation therapy, followed by adjuvant TMZ, it significantly prolongs both progression-free survival (PFS) and overall survival (OS) compared to radiation alone. 3 , 4 , 5 These approaches generally result in a median overall survival of less than one year, 6 – 9 highlighting the importance of optimizing TMZ efficacy in the frontline setting. TMZ has a short half-life of approximately 1.8 h, 10 allowing for rapid clearance, flexible dose adjustments and faster resolution of reactions. 11 Adverse effects of TMZ are common, with nausea and vomiting being the most frequently reported. Cutaneous toxicity occurs in up to 13% of patients, with 90% of cases classified as grade 2 or lower. 12 Although reports of cutaneous toxicity are relatively rare, TMZ-related rashes have been documented as urticarial allergic eruptions, maculopapular rashes, diffuse desquamation, 13 subcutaneous and subdermal plaques and nodules, drug-induced hypersensitivity syndrome (previously referred to as DRESS syndrome), 14 and, in rare cases, Stevens-Johnson syndrome or toxic epidermal necrolysis. 12 , 15 TMZ-induced cutaneous toxicity is thought to be IgE-mediated, often with a delayed onset, making diagnosis challenging, particularly due to the concomitant use of other rash-associated medications such as dapsone or trimethoprim-sulfamethoxazole. 16 Effective management of TMZ toxicity is critical to preventing premature treatment discontinuation in GBM patients; however, standardized guidelines for addressing TMZ-related rashes remain limited. Case reports and case series describe various strategies, including rapid oral desensitization, where TMZ is introduced at a low dose and escalated to the therapeutic dose within a single day, as well as metronomic dosing to reduce the likelihood of recurrent cutaneous toxicity in subsequent cycles. 17 Case report A 25-year-old female with GBM presented with a recurrent rash four months after initiating TMZ. She initially received concurrent TMZ (75 mg/m²) plus radiation for six weeks, followed by maintenance therapy with 280 mg (150 mg/m²) daily on days 1–5 of a 28-day cycle for cycle 1, then 360 mg (200 mg/m²) daily on days 1–5 for cycle 2 and subsequent cycles. On day two of the fourth maintenance cycle, the patient reported a new pruritic rash on her upper and lower extremities. She was advised to hold her day 3 dose and resume treatment on day 4. After taking the day 4 dose, the rash worsened, becoming more pronounced and punctate, with grade 3 pruritus. Subsequent imaging demonstrated slight disease progression with the possibility of pseudoprogression, leading to a regimen change to dose-dense TMZ (100 mg orally on days 1–21 of a 28-day cycle). Given the emergence of a suspected delayed hypersensitivity reaction to TMZ in prior cycles, a desensitization protocol was pursued for the subsequent regimen. Rapid desensitization was designed, with a goal of achieving the planned full therapeutic dose within one day (Table 1 ). Table 1 Day 1 Location: Precision Medicine Clinic Step # Time of planned administration (mins) Dose (mg) # of TMZ capsules 1 0 5 5 mg x 1 2 45 5 5 mg x 1 3 90 10 5 mg x 2 4 120 20 20 mg x 1 5 150 30 5 mg x 2 + 20 mg x 1 6 180 30 5 mg x 2 + 20 mg x 1 Total: 100 Premedication used was cetirizine and famotidine. Utilizing commercially available 5 mg, 20 mg, and 100 mg capsules, doses were established mimicking prior desensitization protocols. After receiving the initial 5 mg dose of TMZ, the patient developed nausea and a pruritic rash, and she was given intravenous hydrocortisone, diphenhydramine, and ondansetron. Physical examination demonstration diffuse urticarial lesions and generalized erythema (Image A). The subsequent dose of TMZ was delayed by four hours to monitor for hypotension or respiratory symptoms, which did not develop, and she successfully completed the desensitization protocol. An ongoing rash was present for the remainder of the cycle. Prior to the start of the subsequent cycle, the patient expressed difficulties complying with the 21-day regimen due to its pill burden, so the treatment plan was changed back to 360 mg (200 mg/m 2 ) daily on days 1–5 of a 28-day cycle. After considering options and alternate therapy, the patient decided to proceed with another attempt at a TMZ desensitization. Though she still had a diffuse urticarial rash from prior cycle, she successfully completed the rapid TMZ desensitization (Table 2 ) while being monitored in the infusion center. Table 2 Day 1 Location: Precision Medicine Clinic Time Medication Dose (mg) # of TMZ capsules 0830 Prednisone 40 0830 Famotidine 20 0830 Diphenhydramine 25 0900 TMZ 5 5 mg x 1 0945 TMZ 5 5 mg x 1 1030 TMZ 10 5 mg x 2 1115 TMZ 20 20 mg x 1 1200 TMZ 30 5 mg x 2 + 20 mg x 1 1245 TMZ 40 20 mg x 2 1330 TMZ 50 5 mg x 2 + 20 mg x 2 1415 TMZ 60 20 mg x 3 1500 TMZ 70 5 mg x 2 + 20 mg x 3 1545 TMZ 70 5 mg x 2 + 20 mg x 3 Total: 360 Premedication with prednisone, famotidine and diphenhydramine was given 30 minutes prior to her first TMZ dose. However, after leaving the infusion center the patient noted an increase in her pruritus and change in her skin lesions. Photos uploaded by the patient to the electronic medical record revealed diffuse erythematous patches (Image B). Symptoms improved with additional prednisone and hydroxyzine. She completed the cycle in her home with stable hypersensitivity symptoms on day two followed by a reduction in rash and pruritus on days 3–5 (Table 3 ). Table 3 Days 2–5 Location: Patient's Home Time Medication Dose (mg) # of TMZ capsules 0830 Prednisone 40 0830 Famotidine 20 0830 Diphenhydramine 25 0900 TMZ 20 20 mg x 1 0945 TMZ 40 20 mg x 2 1030 TMZ 80 20 mg x 4 1115 TMZ 100 100 mg x 1 1200 TMZ 120 20 mg x 1 + 100 mg x 1 Total: 360 Ultimately, she completed five additional cycles over seven months, though her rash persisted as grade 1 throughout these cycles (Image C). She had delays in her treatment from neutropenia and thrombocytopenia despite dose reduction, which ultimately led to a change to a dose-dense schedule of 100 mg seven days on followed by seven days off with a similar desensitization scheme. The patient continued to experience grade 1 pruritus with subsequent exposure to TMZ, though the desensitization and premedication used improved her tolerability and quality of life. Discussion This case report highlights a successful approach to managing TMZ skin hypersensitivity reactions in a patient with GBM. The patient experienced dose-limiting cutaneous hypersensitivity reactions to TMZ, which were effectively managed through a desensitization protocol. This protocol allowed for continued TMZ treatment for 5 cycles over 7 months, demonstrating its potential as a valuable tool in GBM management. The occurrence of multiple unique rashes during TMZ exposure suggests the patient experienced both IgE-mediated hypersensitivity reactions and a fixed drug eruption. This complex presentation aligns with previous reports of varied TMZ-induced cutaneous reactions. 18 The successful management of these diverse reactions through a single desensitization protocol suggests the protocol's effectiveness in addressing different types of hypersensitivity mechanisms. A distinctive aspect of this case is the use of commercially available TMZ capsules (5 mg, 20 mg, and 100 mg) for the desensitization protocol, eliminating the need for specialized compounding. This approach makes the protocol more widely accessible and easier to implement across various clinical settings. The transition from monitored infusion center administration to home-based continuation of the protocol also demonstrates its feasibility for long-term management, which is particularly relevant for the extended treatment courses often required in GBM. The success of this case aligns with and builds upon previous studies on TMZ desensitization. A study of 15 patients with glioma who underwent TMZ desensitization followed by metronomic dosing reported favorable outcomes, with median overall survival of 181.7 months and progression-free survival of 44.9 months. 19 Our case further supports the notion that desensitization can be effectively implemented, even in complex cases involving multiple types of hypersensitivity reactions. The importance of this approach is underscored by the limited treatment options available for GBM, especially in cases of recurrence. TMZ remains a primary chemotherapeutic agent for GBM treatment, and its effectiveness has been demonstrated in various studies. 18 , 19 Bevacizumab is currently FDA approved for refractory GBM, demonstrating an impact on PFS but no significant improvement in OS. 20 By enabling continued TMZ treatment despite initial hypersensitivity reactions, this desensitization protocol may help improve patient outcomes in the face of limited alternatives. While our case demonstrates the potential of TMZ desensitization, further research is needed to optimize and standardize protocols. Prospective studies comparing different desensitization approaches, investigating long-term outcomes, and exploring potential biomarkers to predict hypersensitivity risk could further refine our management strategies. Conclusion TMZ hypersensitivity can hinder the treatment of GBM and other CNS gliomas. This case illustrates that TMZ desensitization protocols represent a valuable addition to GBM treatment that can be implemented with commercially available products and in various practice settings, including the patient’s home. They should be considered for patients experiencing hypersensitivity reactions, as they can extend the use of this critical chemotherapeutic agent. With careful management, these patients may continue to benefit from this crucial therapy, potentially improving their overall treatment outcomes. Declarations Acknowledgements: The authors would like to thank the patient and her family. Compliance with Ethical Standards: Conflict of Interest: All authors declare no conflict of interest. Ethical approval: This article does not contain any studies with human participants performed by any of the authors. Informed consent: Informed consent was obtained from the patient included in the study. Author Contribution Conceptualization: MC, CC, RMM, JLVData Curation: MC, CC, RMMFigures and Tables: MC, CC, RMM, NRWriting - Original Draft: MC, NR, RMM Writing - Review & Editing: SAS, JLVAll authors reviewed the manuscript References van den Bent MJ, Tesileanu CMS, Wick W et al (2021) Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053 – 22054): second interim analysis of a randomised, open-label, phase 3 study. Lancet Oncol 22:813–823. 10.1016/s1470-2045(21)00090-5 Neuroendocrine and Adrenal Tumors (2025) NCCN Clinical Practice Guidelines in Oncology Hart MG, Garside R, Rogers G et al (2013) Temozolomide for high grade glioma. Cochrane Database Syst Rev ; 2013: Cd007415. 20130430. 10.1002/14651858.CD007415.pub2 Cui X, Wang Y, Zhou J et al (2023) Expert opinion on translational research for advanced glioblastoma treatment. Cancer Biology Med 20:344–352. 10.20892/j.issn.2095-3941.2023.0012 Stupp R, Mason WP, Bent, MJvd et al (2005) Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med 352:987–996. 10.1056/NEJMoa043330 Friedman HS, Prados MD, Wen PY et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol ; 27: 4733–4740. 20090831. 10.1200/jco.2008.19.8721 McFarlane T, Rehman N, Wang K et al (2019) Cutaneous toxicities of new targeted cancer therapies: must know for diagnosis, management, and patient-proxy empowerment. Annals Palliat Med 9:1296–1306 Wick W, Puduvalli VK, Chamberlain MC et al (2010) Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 28:1168–117420100201. 10.1200/jco.2009.23.2595 Lombardi G, De Salvo GL, Brandes AA et al (2019) Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol 20:110–119. 10.1016/s1470-2045(18)30675-2 Villano JL, Seery TE, Bressler LR (2009) Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol 64:647–655. 10.1007/s00280-009-1050-5 Chastain DB, Hutzley VJ, Parekh J et al (2019) Antimicrobial Desensitization: A Review of Published Protocols. Pharm (Basel) 7(20190809). 10.3390/pharmacy7030112 Virmani P, Chung E, Thomas AA et al (2015) Cutaneous adverse drug reaction associated with oral temozolomide presenting as dermal and subcutaneous plaques and nodules. JAAD Case Rep 1:286–288. 10.1016/j.jdcr.2015.06.012 Farshchian M, Bardhi R, Daveluy S (2021) Desquamative skin rash associated with temozolomide in a patient with glioblastoma. Dermatol Ther 34:e14771. https://doi.org/10.1111/dth.14771 Mehta H, Gendle CS, Kumaran MS et al (2023) Temozolomide-induced drug rash with eosinophilia and systemic symptoms syndrome. Indian J Dermatol Venereol Leprol 89:160. 10.25259/ijdvl_754_2021 Sarma N (2009) Stevens-Johnson Syndrome and toxic epidermal necrolysis overlap due to oral temozolomide and cranial radiotherapy. Am J Clin Dermatol 10:264–267. 10.2165/00128071-200910040-00007 Deluche E, Leobon S, Touraine F et al (2014) Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma. Curr Oncol 21:e779–781. 10.3747/co.21.2133 Mhanna H, Jiménez Blanco A, Valdez Tejeda M et al (2011) Desensitization to Temozolomide. J Allergy Clin Immunol 127:AB197. 10.1016/j.jaci.2010.12.783 Sun S, Lee D, Lee NP et al (2012) Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide. J Neurooncol 109:467–47520120705. 10.1007/s11060-012-0923-3 Neth BJ, Ruff MW, Uhm JH et al (2020) Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity. Cancer Chemother Pharmacol 86(20200810):375–382. 10.1007/s00280-020-04123-y Sferruzza G, Malcangi M, Bosco L et al (2024) Reassessing the efficacy of bevacizumab in newly diagnosed glioblastoma: A systematic review and external pseudodata-based analysis. Neuro-Oncology Adv 6. 10.1093/noajnl/vdad174 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Jun, 2025 Read the published version in Cancer Chemotherapy and Pharmacology → Version 1 posted Editorial decision: Revision requested 09 May, 2025 Reviews received at journal 06 May, 2025 Reviewers agreed at journal 06 May, 2025 Reviews received at journal 05 May, 2025 Reviewers agreed at journal 22 Apr, 2025 Reviewers invited by journal 01 Apr, 2025 Editor assigned by journal 01 Apr, 2025 Submission checks completed at journal 01 Apr, 2025 First submitted to journal 29 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6334053","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":445106594,"identity":"42d5402f-9aa5-4803-bfca-fa0a275e6965","order_by":0,"name":"Morgan Cantley","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYLCCByCCvQFIGFgQpYGxIQFE8RwAaZEgRYsEhCSsnr/97PEHCRWHo/kln1/d8KNAAijSnYBXi8SZvMSGhDOHc2fOzim72QN0mMSZsxvwajFgyDFsSGw7nLvhdk7aDR6gFgOJXAJa+N8Atfw7nLv/5pm0m3+I0iIBsqUBaIsE+7HbRNkiceON4YyEY+m5M87ksN2WMZDgIegX/v4cgw8faqxz+9uPP7v55o+NHH97L34tUNAMxDwGIBYPMcpBoA6I2R8Qq3oUjIJRMApGGAAAQyBNZhesP0IAAAAASUVORK5CYII=","orcid":"","institution":"University of Kentucky","correspondingAuthor":true,"prefix":"","firstName":"Morgan","middleName":"","lastName":"Cantley","suffix":""},{"id":445106595,"identity":"02db3f58-15ce-4eb7-82e3-57ae4ead9671","order_by":1,"name":"Clyde Coleman","email":"","orcid":"","institution":"University of Kentucky","correspondingAuthor":false,"prefix":"","firstName":"Clyde","middleName":"","lastName":"Coleman","suffix":""},{"id":445106596,"identity":"0c2ef2b7-0cc1-4e64-8ef9-9c6693738e16","order_by":2,"name":"Rachael M. Morgan","email":"","orcid":"","institution":"University of Kentucky","correspondingAuthor":false,"prefix":"","firstName":"Rachael","middleName":"M.","lastName":"Morgan","suffix":""},{"id":445106598,"identity":"6de3d5ae-3d0b-4b07-b88e-fdaba47ec67c","order_by":3,"name":"Niharika Reddy","email":"","orcid":"","institution":"University of Kentucky","correspondingAuthor":false,"prefix":"","firstName":"Niharika","middleName":"","lastName":"Reddy","suffix":""},{"id":445106599,"identity":"5cd9ca80-11fc-4eb3-9ef1-0cb6ae567d22","order_by":4,"name":"Sarah A. Sertich","email":"","orcid":"","institution":"University of Kentucky","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"A.","lastName":"Sertich","suffix":""},{"id":445106600,"identity":"2797ed14-086d-45a8-9c56-55771f69138d","order_by":5,"name":"John L. Villano","email":"","orcid":"","institution":"University of Kentucky","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"L.","lastName":"Villano","suffix":""}],"badges":[],"createdAt":"2025-03-29 12:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6334053/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6334053/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00280-025-04782-9","type":"published","date":"2025-06-20T15:56:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82083854,"identity":"1f5f90c1-deec-4510-8814-82bb996ac97b","added_by":"auto","created_at":"2025-05-06 14:52:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3041297,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003ePatient’s left leg immediately following the first dose TMZ during rapid desensitization. The skin shows diffuse polymorphic urticarial lesions, some with central clearing, admixed with erythematous macules on a base of confluent pinkplaques.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB.\u003c/strong\u003ePatient’s left leg after completing rapid densitization to dose dense TMZ. There are diffuse irregular, well-circumscribed erythematous patches most prominent on the lower extremities on a background of faint pink nonconfluent patches. Notably, there is less total body surface area involved than during the prior desensitization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC.\u003c/strong\u003e Patient’s left leg following multiple rounds of desensitization. There are polymorphic nonpalpable ovaloid lesions with a prominent erythematous rim, many with central clearing, on a background of diffuse faint punctate erythematous macules.\u003c/p\u003e","description":"","filename":"floatimage13.png","url":"https://assets-eu.researchsquare.com/files/rs-6334053/v1/18bb8d6aa98db077d77d499d.png"},{"id":85231596,"identity":"e28e2d18-d5db-482a-950a-920e175a75b5","added_by":"auto","created_at":"2025-06-23 16:09:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4400980,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6334053/v1/8361bbb7-19bf-49a1-bd1f-2a26fbed81e1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Novel Desensitization Protocol Utilizing Conventional Formulations to Mitigate Temozolomide-Related Skin Hypersensitivity","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTemozolomide (TMZ) is an oral alkylating agent with antitumor activity across various malignancies, including glioblastomas, newly diagnosed and refractory anaplastic astrocytoma.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e TMZ can also be used in progression of neuroendocrine tumors of the gastrointestinal tract.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e It is most widely used for GBM as when administered concurrently with radiation therapy, followed by adjuvant TMZ, it significantly prolongs both progression-free survival (PFS) and overall survival (OS) compared to radiation alone.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e These approaches generally result in a median overall survival of less than one year, \u003csup\u003e\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e highlighting the importance of optimizing TMZ efficacy in the frontline setting.\u003c/p\u003e \u003cp\u003eTMZ has a short half-life of approximately 1.8 h,\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e allowing for rapid clearance, flexible dose adjustments and faster resolution of reactions.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Adverse effects of TMZ are common, with nausea and vomiting being the most frequently reported. Cutaneous toxicity occurs in up to 13% of patients, with 90% of cases classified as grade 2 or lower.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Although reports of cutaneous toxicity are relatively rare, TMZ-related rashes have been documented as urticarial allergic eruptions, maculopapular rashes, diffuse desquamation,\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e subcutaneous and subdermal plaques and nodules, drug-induced hypersensitivity syndrome (previously referred to as DRESS syndrome),\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e and, in rare cases, Stevens-Johnson syndrome or toxic epidermal necrolysis.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e TMZ-induced cutaneous toxicity is thought to be IgE-mediated, often with a delayed onset, making diagnosis challenging, particularly due to the concomitant use of other rash-associated medications such as dapsone or trimethoprim-sulfamethoxazole.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Effective management of TMZ toxicity is critical to preventing premature treatment discontinuation in GBM patients; however, standardized guidelines for addressing TMZ-related rashes remain limited. Case reports and case series describe various strategies, including rapid oral desensitization, where TMZ is introduced at a low dose and escalated to the therapeutic dose within a single day, as well as metronomic dosing to reduce the likelihood of recurrent cutaneous toxicity in subsequent cycles.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 25-year-old female with GBM presented with a recurrent rash four months after initiating TMZ. She initially received concurrent TMZ (75 mg/m\u0026sup2;) plus radiation for six weeks, followed by maintenance therapy with 280 mg (150 mg/m\u0026sup2;) daily on days 1\u0026ndash;5 of a 28-day cycle for cycle 1, then 360 mg (200 mg/m\u0026sup2;) daily on days 1\u0026ndash;5 for cycle 2 and subsequent cycles. On day two of the fourth maintenance cycle, the patient reported a new pruritic rash on her upper and lower extremities. She was advised to hold her day 3 dose and resume treatment on day 4. After taking the day 4 dose, the rash worsened, becoming more pronounced and punctate, with grade 3 pruritus. Subsequent imaging demonstrated slight disease progression with the possibility of pseudoprogression, leading to a regimen change to dose-dense TMZ (100 mg orally on days 1\u0026ndash;21 of a 28-day cycle).\u003c/p\u003e \u003cp\u003eGiven the emergence of a suspected delayed hypersensitivity reaction to TMZ in prior cycles, a desensitization protocol was pursued for the subsequent regimen. Rapid desensitization was designed, with a goal of achieving the planned full therapeutic dose within one day (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDay 1\u0026ensp;\u0026ensp;\u0026ensp;\u0026ensp;Location: Precision Medicine Clinic\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStep #\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime of planned administration (mins)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDose (mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e# of TMZ capsules\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u0026thinsp;+\u0026thinsp;20 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u0026thinsp;+\u0026thinsp;20 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eTotal: 100\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePremedication used was cetirizine and famotidine. Utilizing commercially available 5 mg, 20 mg, and 100 mg capsules, doses were established mimicking prior desensitization protocols. After receiving the initial 5 mg dose of TMZ, the patient developed nausea and a pruritic rash, and she was given intravenous hydrocortisone, diphenhydramine, and ondansetron. Physical examination demonstration diffuse urticarial lesions and generalized erythema (Image A).\u003c/p\u003e \u003cp\u003eThe subsequent dose of TMZ was delayed by four hours to monitor for hypotension or respiratory symptoms, which did not develop, and she successfully completed the desensitization protocol. An ongoing rash was present for the remainder of the cycle.\u003c/p\u003e \u003cp\u003ePrior to the start of the subsequent cycle, the patient expressed difficulties complying with the 21-day regimen due to its pill burden, so the treatment plan was changed back to 360 mg (200 mg/m\u003csup\u003e2\u003c/sup\u003e) daily on days 1\u0026ndash;5 of a 28-day cycle. After considering options and alternate therapy, the patient decided to proceed with another attempt at a TMZ desensitization. Though she still had a diffuse urticarial rash from prior cycle, she successfully completed the rapid TMZ desensitization (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) while being monitored in the infusion center.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDay 1\u0026ensp;\u0026ensp;\u0026ensp;\u0026ensp;Location: Precision Medicine Clinic\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDose (mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e# of TMZ capsules\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrednisone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFamotidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiphenhydramine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0945\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u0026thinsp;+\u0026thinsp;20 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u0026thinsp;+\u0026thinsp;20 mg x 2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u0026thinsp;+\u0026thinsp;20 mg x 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1545\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 mg x 2\u0026thinsp;+\u0026thinsp;20 mg x 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eTotal: 360\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePremedication with prednisone, famotidine and diphenhydramine was given 30 minutes prior to her first TMZ dose. However, after leaving the infusion center the patient noted an increase in her pruritus and change in her skin lesions. Photos uploaded by the patient to the electronic medical record revealed diffuse erythematous patches (Image B).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSymptoms improved with additional prednisone and hydroxyzine. She completed the cycle in her home with stable hypersensitivity symptoms on day two followed by a reduction in rash and pruritus on days 3\u0026ndash;5 (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDays 2\u0026ndash;5\u0026ensp;\u0026ensp;\u0026ensp;\u0026ensp;Location: Patient's Home\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDose (mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e# of TMZ capsules\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrednisone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFamotidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiphenhydramine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0945\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 mg x 1\u0026thinsp;+\u0026thinsp;100 mg x 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eTotal: 360\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eUltimately, she completed five additional cycles over seven months, though her rash persisted as grade 1 throughout these cycles (Image C).\u003c/p\u003e \u003cp\u003eShe had delays in her treatment from neutropenia and thrombocytopenia despite dose reduction, which ultimately led to a change to a dose-dense schedule of 100 mg seven days on followed by seven days off with a similar desensitization scheme. The patient continued to experience grade 1 pruritus with subsequent exposure to TMZ, though the desensitization and premedication used improved her tolerability and quality of life.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case report highlights a successful approach to managing TMZ skin hypersensitivity reactions in a patient with GBM. The patient experienced dose-limiting cutaneous hypersensitivity reactions to TMZ, which were effectively managed through a desensitization protocol. This protocol allowed for continued TMZ treatment for 5 cycles over 7 months, demonstrating its potential as a valuable tool in GBM management. The occurrence of multiple unique rashes during TMZ exposure suggests the patient experienced both IgE-mediated hypersensitivity reactions and a fixed drug eruption. This complex presentation aligns with previous reports of varied TMZ-induced cutaneous reactions.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e The successful management of these diverse reactions through a single desensitization protocol suggests the protocol's effectiveness in addressing different types of hypersensitivity mechanisms.\u003c/p\u003e \u003cp\u003eA distinctive aspect of this case is the use of commercially available TMZ capsules (5 mg, 20 mg, and 100 mg) for the desensitization protocol, eliminating the need for specialized compounding. This approach makes the protocol more widely accessible and easier to implement across various clinical settings. The transition from monitored infusion center administration to home-based continuation of the protocol also demonstrates its feasibility for long-term management, which is particularly relevant for the extended treatment courses often required in GBM. The success of this case aligns with and builds upon previous studies on TMZ desensitization. A study of 15 patients with glioma who underwent TMZ desensitization followed by metronomic dosing reported favorable outcomes, with median overall survival of 181.7 months and progression-free survival of 44.9 months.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Our case further supports the notion that desensitization can be effectively implemented, even in complex cases involving multiple types of hypersensitivity reactions.\u003c/p\u003e \u003cp\u003eThe importance of this approach is underscored by the limited treatment options available for GBM, especially in cases of recurrence. TMZ remains a primary chemotherapeutic agent for GBM treatment, and its effectiveness has been demonstrated in various studies.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Bevacizumab is currently FDA approved for refractory GBM, demonstrating an impact on PFS but no significant improvement in OS.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e By enabling continued TMZ treatment despite initial hypersensitivity reactions, this desensitization protocol may help improve patient outcomes in the face of limited alternatives. While our case demonstrates the potential of TMZ desensitization, further research is needed to optimize and standardize protocols. Prospective studies comparing different desensitization approaches, investigating long-term outcomes, and exploring potential biomarkers to predict hypersensitivity risk could further refine our management strategies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTMZ hypersensitivity can hinder the treatment of GBM and other CNS gliomas. This case illustrates that TMZ desensitization protocols represent a valuable addition to GBM treatment that can be implemented with commercially available products and in various practice settings, including the patient\u0026rsquo;s home. They should be considered for patients experiencing hypersensitivity reactions, as they can extend the use of this critical chemotherapeutic agent. With careful management, these patients may continue to benefit from this crucial therapy, potentially improving their overall treatment outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eThe authors would like to thank the patient and her family.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e All authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e This article does not contain any studies with human participants performed by any of the authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u003c/strong\u003e Informed consent was obtained from the patient included in the study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: MC, CC, RMM, JLVData Curation: MC, CC, RMMFigures and Tables: MC, CC, RMM, NRWriting - Original Draft: MC, NR, RMM Writing - Review \u0026amp; Editing: SAS, JLVAll authors reviewed the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003evan den Bent MJ, Tesileanu CMS, Wick W et al (2021) Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053\u0026thinsp;\u0026ndash;\u0026thinsp;22054): second interim analysis of a randomised, open-label, phase 3 study. Lancet Oncol 22:813\u0026ndash;823. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1470-2045(21)00090-5\u003c/span\u003e\u003cspan address=\"10.1016/s1470-2045(21)00090-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeuroendocrine and Adrenal Tumors (2025) \u003cem\u003eNCCN Clinical Practice Guidelines in Oncology\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHart MG, Garside R, Rogers G et al (2013) Temozolomide for high grade glioma. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e ; 2013: Cd007415. 20130430. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD007415.pub2\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD007415.pub2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCui X, Wang Y, Zhou J et al (2023) Expert opinion on translational research for advanced glioblastoma treatment. Cancer Biology Med 20:344\u0026ndash;352. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.20892/j.issn.2095-3941.2023.0012\u003c/span\u003e\u003cspan address=\"10.20892/j.issn.2095-3941.2023.0012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStupp R, Mason WP, Bent, MJvd et al (2005) Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med 352:987\u0026ndash;996. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa043330\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa043330\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedman HS, Prados MD, Wen PY et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. \u003cem\u003eJ Clin Oncol\u003c/em\u003e ; 27: 4733\u0026ndash;4740. 20090831. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/jco.2008.19.8721\u003c/span\u003e\u003cspan address=\"10.1200/jco.2008.19.8721\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcFarlane T, Rehman N, Wang K et al (2019) Cutaneous toxicities of new targeted cancer therapies: must know for diagnosis, management, and patient-proxy empowerment. Annals Palliat Med 9:1296\u0026ndash;1306\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWick W, Puduvalli VK, Chamberlain MC et al (2010) Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 28:1168\u0026ndash;117420100201. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/jco.2009.23.2595\u003c/span\u003e\u003cspan address=\"10.1200/jco.2009.23.2595\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLombardi G, De Salvo GL, Brandes AA et al (2019) Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol 20:110\u0026ndash;119. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1470-2045(18)30675-2\u003c/span\u003e\u003cspan address=\"10.1016/s1470-2045(18)30675-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVillano JL, Seery TE, Bressler LR (2009) Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol 64:647\u0026ndash;655. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00280-009-1050-5\u003c/span\u003e\u003cspan address=\"10.1007/s00280-009-1050-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChastain DB, Hutzley VJ, Parekh J et al (2019) Antimicrobial Desensitization: A Review of Published Protocols. Pharm (Basel) 7(20190809). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/pharmacy7030112\u003c/span\u003e\u003cspan address=\"10.3390/pharmacy7030112\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVirmani P, Chung E, Thomas AA et al (2015) Cutaneous adverse drug reaction associated with oral temozolomide presenting as dermal and subcutaneous plaques and nodules. JAAD Case Rep 1:286\u0026ndash;288. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jdcr.2015.06.012\u003c/span\u003e\u003cspan address=\"10.1016/j.jdcr.2015.06.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarshchian M, Bardhi R, Daveluy S (2021) Desquamative skin rash associated with temozolomide in a patient with glioblastoma. Dermatol Ther 34:e14771. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/dth.14771\u003c/span\u003e\u003cspan address=\"10.1111/dth.14771\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehta H, Gendle CS, Kumaran MS et al (2023) Temozolomide-induced drug rash with eosinophilia and systemic symptoms syndrome. Indian J Dermatol Venereol Leprol 89:160. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.25259/ijdvl_754_2021\u003c/span\u003e\u003cspan address=\"10.25259/ijdvl_754_2021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarma N (2009) Stevens-Johnson Syndrome and toxic epidermal necrolysis overlap due to oral temozolomide and cranial radiotherapy. Am J Clin Dermatol 10:264\u0026ndash;267. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2165/00128071-200910040-00007\u003c/span\u003e\u003cspan address=\"10.2165/00128071-200910040-00007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeluche E, Leobon S, Touraine F et al (2014) Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma. Curr Oncol 21:e779\u0026ndash;781. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3747/co.21.2133\u003c/span\u003e\u003cspan address=\"10.3747/co.21.2133\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMhanna H, Jim\u0026eacute;nez Blanco A, Valdez Tejeda M et al (2011) Desensitization to Temozolomide. J Allergy Clin Immunol 127:AB197. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jaci.2010.12.783\u003c/span\u003e\u003cspan address=\"10.1016/j.jaci.2010.12.783\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun S, Lee D, Lee NP et al (2012) Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide. J Neurooncol 109:467\u0026ndash;47520120705. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11060-012-0923-3\u003c/span\u003e\u003cspan address=\"10.1007/s11060-012-0923-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeth BJ, Ruff MW, Uhm JH et al (2020) Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity. Cancer Chemother Pharmacol 86(20200810):375\u0026ndash;382. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00280-020-04123-y\u003c/span\u003e\u003cspan address=\"10.1007/s00280-020-04123-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSferruzza G, Malcangi M, Bosco L et al (2024) Reassessing the efficacy of bevacizumab in newly diagnosed glioblastoma: A systematic review and external pseudodata-based analysis. Neuro-Oncology Adv 6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/noajnl/vdad174\u003c/span\u003e\u003cspan address=\"10.1093/noajnl/vdad174\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cancer-chemotherapy-and-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccap","sideBox":"Learn more about [Cancer Chemotherapy and Pharmacology](http://link.springer.com/journal/280)","snPcode":"280","submissionUrl":"https://submission.nature.com/new-submission/280/3","title":"Cancer Chemotherapy and Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Glioblastoma, temozolomide, desensitization, rash, drug-induced reactions","lastPublishedDoi":"10.21203/rs.3.rs-6334053/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6334053/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTemozolomide (TMZ) is an oral alkylating agent used in the first-line treatment regimen for glioblastoma (GBM). Multiple documented cases of dose-limiting TMZ rash utilize desensitization protocols requiring complex TMZ dosing and dilutions. We report a TMZ-related skin hypersensitivity managed by a desensitization protocol utilizing only commercially available dosage forms of TMZ. This protocol allowed the patient to continue optimal treatment for GBM without the need for complicated compounding and dilution efforts.\u003c/p\u003e","manuscriptTitle":"Novel Desensitization Protocol Utilizing Conventional Formulations to Mitigate Temozolomide-Related Skin Hypersensitivity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 14:52:45","doi":"10.21203/rs.3.rs-6334053/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-09T05:04:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-07T01:33:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139791779954798311611878400492037152646","date":"2025-05-06T14:42:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-05T13:23:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109893852853065724463686854455460226760","date":"2025-04-22T15:48:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-01T14:36:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-01T09:46:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-01T09:44:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cancer Chemotherapy and Pharmacology","date":"2025-03-29T12:08:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cancer-chemotherapy-and-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccap","sideBox":"Learn more about [Cancer Chemotherapy and Pharmacology](http://link.springer.com/journal/280)","snPcode":"280","submissionUrl":"https://submission.nature.com/new-submission/280/3","title":"Cancer Chemotherapy and Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"638419af-58d7-466c-909c-3d5f5d8870a8","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-23T16:06:20+00:00","versionOfRecord":{"articleIdentity":"rs-6334053","link":"https://doi.org/10.1007/s00280-025-04782-9","journal":{"identity":"cancer-chemotherapy-and-pharmacology","isVorOnly":false,"title":"Cancer Chemotherapy and Pharmacology"},"publishedOn":"2025-06-20 15:56:59","publishedOnDateReadable":"June 20th, 2025"},"versionCreatedAt":"2025-05-06 14:52:45","video":"","vorDoi":"10.1007/s00280-025-04782-9","vorDoiUrl":"https://doi.org/10.1007/s00280-025-04782-9","workflowStages":[]},"version":"v1","identity":"rs-6334053","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6334053","identity":"rs-6334053","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}