Associations between skin rash, treatment outcome, and single nucleotide polymorphisms in head and neck cancer patients receiving the EGFR-inhibitor zalutumumab: results from the DAHANCA 19 trial

Brøndum, Line; Sørensen, Brita Singers; Maare, C.; Johansen, Jørgen; Primdahl, Hanne; Evensen, Jan F.; Kristensen, Claus Andrup; Andersen, Lisbeth Juhler; Overgaard, Jens; Eriksen, Jesper Grau

doi:10.1080/0284186x.2018.1464664

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…48,51 2.1.3 | Tyrosine kinase receptor: neurotrophic receptor tyrosine kinase (NTRK) inhibitors NTRK inhibitors (entrectinib, larotrectinib) have been recently approved to treat NTRK fusion-positive solid tumors in children, such as infantile fibrosarcomas [52][53][54]. Preliminary reports of the ongoing STARTRK-NG clinical trial studying entrectinib have not noted any dose-limiting dermatologic AEs 55.…”

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confidence: 99%

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Carlberg

Davies

Brandling‐Bennett

et al. 2020

Pediatric Dermatology

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The incidence of cancer from birth to 20 years of age is 18.7 per 100 000 and continues to increase. 1 Although mortality has steadily declined, cancer remains one of the leading causes of death from disease in pediatric patients. Targeted anticancer therapies are among the most recently developed agents to address this issue. 2 Key tenets of oncogenesis include uncontrolled cellular growth, tumor metastasis, and evasion of host defenses. 3 Targeted anticancer therapies are small-molecule drugs or monoclonal antibodies that interrupt oncogenesis through a variety of mechanisms (Figure 1). 4 They can act directly on cancer cells to affect cellular proliferation, differentiation, or apoptosis. 3,4 They may also inhibit tumor vasculature, reducing nutrients required for tumor growth or the potential for tumor metastasis. 3,4 Moreover, they may act on immune checkpoint proteins, activating the body's response to cancer. 3,4 This latter mechanism of action is known as targeted immunotherapy. 3-5 As the molecular basis of a specific cancer is uncovered, and particular signaling molecules are found to be upregulated, candidate targeted therapies provide greater specificity than traditional chemotherapy which non-selectively inhibits all rapidly dividing cells. This "precision medicine" has shifted treatment from using medications to target a class of diseases to choosing medications targeting the molecular pathways underpinning disease. Targeted therapies have different side-effect profiles than conventional cytotoxic agents, which were covered in Part I of this two-part series. 6,7 The adverse events (AEs) from targeted therapies may be limited to tissues uniquely targeted by these

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confidence: 99%

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Carlberg

Davies

Brandling‐Bennett

et al. 2020

Pediatric Dermatology

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“…Interestingly, although skin toxicity from other agents, such as epidermal growth factor receptor inhibitors, has been directly associated with improved survival outcomes, this association has received less attention with regorafenib and related agents [10, 15, 16]. For example, in a retrospective study of only 40 patients, Ochi and others reported a longer median survival among patients who developed HFSR [16].…”

Section: Discussionmentioning

confidence: 99%

“…Quality of life is also reported. Overall survival/progression‐free survival (PFS) based on HSFR is also reported [9–13]. Overall survival (OS) is defined as time from day after cycle 1 end date to death due to any cause.…”

Section: Methodsmentioning

confidence: 99%

Preemptive Versus Reactive Topical Clobetasol for Regorafenib-Induced Hand-Foot Reactions: A Preplanned Analysis of the ReDOS Trial

Jatoi

Ahn

et al. 2021

The Oncologist

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Background Hand‐foot skin reaction (HFSR) is the most common regorafenib‐induced adverse event and is in need of effective prevention and palliation. Materials and Methods The Regorafenib Dose Optimization Study (ReDOS), a four‐arm, previously published trial with a 1:1:1:1 randomization scheme, was analyzed in a manner in keeping with the original protocol to assess whether clobetasol 0.05% cream (a corticosteroid) applied to the palms and soles twice per day for 8 weeks was more effective when prescribed preemptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the first two cycles of regorafenib. Results Sixty‐one patients received preemptive clobetasol, and 55 received reactive clobetasol. Groups were balanced on demographics. Over the first two cycles, no evidence of HFSR occurred in 30% with preemptive clobetasol versus 13% with reactive clobetasol (p = .03). During the first cycle, 54% and 45% of patients had no HFSR with preemptive and reactive clobetasol, respectively (p = .35). During the second cycle, 33% and 15% had no HFSR with preemptive and reactive clobetasol, respectively (p = .02). During the second cycle, rates of grade 1, 2, and 3 HFSR were 30%, 8%, and 3%, respectively, with preemptive clobetasol and 43%, 18%, and 7%, respectively, with reactive clobetasol (p = .12). Patient‐reported outcomes showed HFSR compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol. No clobetasol‐induced adverse events were reported. Conclusion Preemptive clobetasol might lessen regorafenib‐induced hand‐foot reactions compared with reactive therapy. Further confirmatory studies are needed in a larger patient cohort. Implications for Practice Regorafenib causes hand‐foot skin reactions. Preemptive clobetasol, a high‐potency topical corticosteroid, appears to lessen the severity of this adverse event. Although further study is needed, the favorable adverse event profile of this intervention might prompt clinicians to discuss this option with their patients.

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“… 408 Meanwhile, moderate-to-severe skin rash during zalutumumab treatment was related to superior OS, independent of HPV infection and p16 status. 409 …”

Section: Targeted Therapy In Clinicalmentioning

confidence: 99%

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Tie

Alu

et al. 2023

Sig Transduct Target Ther

101

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Head and neck cancer (HNC) is malignant, genetically complex and difficult to treat and is the sixth most frequent cancer, with tobacco, alcohol and human papillomavirus being major risk factors. Based on epigenetic data, HNC is remarkably heterogeneous, and treatment remains challenging. There is a lack of significant improvement in survival and quality of life in patients with HNC. Over half of HNC patients experience locoregional recurrence or distal metastasis despite the current multiple traditional therapeutic strategies and immunotherapy. In addition, resistance to chemotherapy, radiotherapy and some targeted therapies is common. Therefore, it is urgent to explore more effective and tolerable targeted therapies to improve the clinical outcomes of HNC patients. Recent targeted therapy studies have focused on identifying promising biomarkers and developing more effective targeted therapies. A well understanding of the pathogenesis of HNC contributes to learning more about its inner association, which provides novel insight into the development of small molecule inhibitors. In this review, we summarized the vital signaling pathways and discussed the current potential therapeutic targets against critical molecules in HNC, as well as presenting preclinical animal models and ongoing or completed clinical studies about targeted therapy, which may contribute to a more favorable prognosis of HNC. Targeted therapy in combination with other therapies and its limitations were also discussed.

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Associations between skin rash, treatment outcome, and single nucleotide polymorphisms in head and neck cancer patients receiving the EGFR-inhibitor zalutumumab: results from the DAHANCA 19 trial

Cited by 9 publications

References 33 publications

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Preemptive Versus Reactive Topical Clobetasol for Regorafenib-Induced Hand-Foot Reactions: A Preplanned Analysis of the ReDOS Trial

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

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