Skin Reaction to Cetuximab as a Criterion for Treatment Selection in Head and Neck Cancer

Strojan, Primož; Zakotnik, Branko; Žumer, Barbara; Karner, Katarina; Dremelj, Marta; Jančar, Boris; Jereb, Simona; Grašič-Kuhar, Cvetka

doi:10.21873/anticanres.12717

Cited by 5 publications

(4 citation statements)

References 27 publications

(35 reference statements)

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“…This is considerably higher than in the EXTREME study. We reported a similar rate in our previous study (7). Secondly, the incidence of a grade 3 skin reaction (Table V) was also high: 27.3% in comparison to 9% in the EXTREME study.…”

Section: Univariate Analysissupporting

confidence: 86%

“…We followed the international treatment guidelines (6), but the treatment with cetuximab was not fully reimbursed in the first years after European Medicine Agency (EMA) approval, and our patient population is also specific regarding the high percentage (20-25%) of grade 3 or 4 infusion reactions to cetuximab, which prevented our patients from receiving cetuximab (7). The primary aim of this retrospective study was to compare the outcomes of our patients with R/M SCHNC treated with the PF and PFE regimens in the routine clinical setting with outcome in a randomized trial and to identify possible prognostic factors for PFS and OS.…”

Section: Introductionmentioning

confidence: 99%

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Outcome of patients with recurrent/metastatic squamous cell head and neck cancer treated with platinum‑based chemotherapy with or without cetuximab in real‑world practice

2021

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Patients with recurrent or metastatic squamous cell head and neck cancer (R/M SCHNC) exhibit a poor prognosis with a median overall survival (OS) time of <1 year. Platinum-based chemotherapy with or without cetuximab has been the standard of care in the last decade. The aim of the current retrospective study was to evaluate the outcome and tolerability of treatment in patients with R/M SCHNC receiving platinum/5-fluorouracil/cetuximab (PFE) chemotherapy compared with platinum/5-fluorouracil (PF) chemotherapy in daily clinical practice. A retrospective analysis was performed using the data of patients treated at the Institute of Oncology Ljubljana between April 2008 and May 2018. Progression-free survival (PFS) and OS were calculated with the Kaplan-Meier method and compared with the log-rank test. Multivariate regression Cox analysis was used to determine independent prognostic factors. A total of 67 patients were treated at the aforementioned Institute: 34 patients received the PF and 33 the PFE regimen. The mean age of patients was 54.6 years and 91% of patients were male. Median PFS time was 6.6 vs. 7.1 months for the PF vs. PFE groups, respectively (P=0.852). Median OS time was 9.6 vs. 11.5 months for the PF vs. PFE groups, respectively (P=0.029). The prognostic factor for PFS was partial remission [hazard ratio (HR), 0.32; 95% CI, 0.15-0.70; P=0.004]. Prognostic factors for OS were partial remission (HR, 0.15; 95% CI, 0.06-0.38; P<0.001) or stable disease (HR, 0.28; 95% CI, 0.13-0.64; P=0.002), and a subsequent line of treatment upon progression (HR, 0.28; 95% CI, 0.15-0.52; P<0.001). In the PFE group, 15.4% of patients had a grade >2 infusion reaction to cetuximab and 27.3% had grade 3 skin rash. There were no differences in diarrhoea, hypomagnesaemia, infections and febrile neutropenia; however, the mortality on active treatment was high (13.4%). In conclusion, patients treated with PFE had similar PFS, but improved OS compared with patients treated with the PF protocol. The proportion of patients who died under treatment due to disease progression and toxicity was high in both treatment arms. A thorough selection of patients for this treatment is crucial.

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Section: Univariate Analysissupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Outcome of patients with recurrent/metastatic squamous cell head and neck cancer treated with platinum‑based chemotherapy with or without cetuximab in real‑world practice

2021

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“…To assess the efficacy of ExRT compared with ChRT for locally advanced HNSCC patients, we included 25 trials. 15–20,23–41 In human papillomavirus (HPV)-positive subgroups which compared the efficacy of ExRT with that of ChRT, six trials were included. 16,34,39,40,42,43 The subgroups comparing ExRT with RT included five studies, and the data were retrieved only for analyzing the safety of ExRT in contrast to ChRT/RT for locally advanced HNSCC patients.…”

Section: Resultsmentioning

confidence: 99%

Comparative efficacy and safety of radiotherapy/cetuximabversusradiotherapy/chemotherapy for locally advanced head and neck squamous cell carcinoma patients: a systematic review of published, primarily non-randomized, data

et al. 2020

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Background: Cetuximab (CTX) has been approved to be administered concurrently with radiotherapy (RT) to treat locally advanced head and neck squamous cell carcinoma (HNSCC). The aim of this study was to assess the efficacy and safety of concurrent CTX with RT (ExRT). Method: The PubMed, Cochrane Library, EMBASE databases were systematically searched to find relevant articles. The combined hazard ratio (HR), risk ratio (RR) and 95% confidence interval were calculated to assess the efficacy and safety of ExRT in contrast to concurrent platinum-based chemotherapy with RT (ChRT). Results: In total, 32 articles with 4556 patients were included. The pooled HRs indicated that ExRT achieved an unfavorable overall survival (HR: 1.86, p < 0.0001), disease-specific survival (HR: 2.58, p = 0.002), locoregional control (HR: 1.94, p < 0.00001), and progression-free survival (HR: 2.04, p = 0.003) compared with ChRT for locally advanced HNSCC patients. In human papillomavirus-positive patient subgroups, ExRT showed inferior disease-specific survival (HR: 2.55, p = 0.009) and locoregional control (HR: 2.27, p < 0.0001) in contrast to ChRT. Additionally, ExRT increased the occurrence of mucositis (RR: 1.17, p < 0.005), skin toxicity (RR: 6.26, p < 0.00001), and infection (RR: 2.27, p = 0.04) compared with non-CTX groups (ChRT and RT), and was associated with lower incidence of anemia (RR: 0.35, p = 0.009), leukocytopenia (RR: 0.17, p < 0.0001), neutropenia (RR: 0.06, p < 0.0001), nausea/vomiting (RR: 0.23, p < 0.0001), and renal toxicity (RR: 0.14, p = 0.007). Conclusion: ChRT should remain the standard treatment for locally advanced HNSCC patients. ExRT was recognized as an effective alternative treatment for locally advanced HNSCC patients who experienced unbearable toxicities caused by non-CTX treatments.

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“…EGFR is a critical therapeutic target in cancer. In clinical stage, the anti-EGFR therapy trials in colorectal cancer [30] , biliary cancer [31] , head and neck cancer [32] , non-melanoma cancer [33] , lung cancer [34] , etc. have been performed.…”

Section: Discussionmentioning

confidence: 99%

Carnosol Induces Cell Apoptosis and Inhibits Invasion and Proliferation in Skin Epidermoid Cancer in Vitro Through MMP11-EGFR Pathway

Jiang

Liu

Zhang

et al. 2021

Preprint

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Background and purpose: The anti-tumor effect of carnosol has been revealed in cancers. This research intends to explore the role and underlying mechanisms of carnosol in the skin cancer in vitro. Methods: Online database GEPIA was used to preliminarily analyze MMP11 expression in skin cancer and further performed overall survival evaluation based on TCGA data. 0, 5µM, 10 µM, 20 µM carnosol was added into the skin cancer A431 cell culture. Later, RT-PCR method detected the mRNA expression of MMP-11 and Elisa kits measured the concentrations of MMP11, phosphor-EGFR and total EGFR proteins as well as the biomarkers related to proliferation (Ki67) and EMT (E-cadherin and Vimentin) as well as Casepase-3. The 20µM carnosol group was selected to further study the regulatory effect of MMP11 in A431 cells.Colony formation examined the cell proliferation. Flow cytometry method checked cell apoptosis while Transwell method explored the cell invasion and migration. Results: MMP11 is upregulated in skin cancer and lower level of MMP11 or EGFR expression is correlated with higher overall survival rates. Carnosol addition inhibited the mRNA expression of MMP11 and lowered the protein concentrations of MMP11 and phosphor-EGFR. In addition, Ki67 and Vimentin concentration was inhibited by carnosol while E-cadherin was instead promoted. Caspase-3 activity was enhanced by carnosol. Upregulation of MMP11 recovered EGFR activation, cell proliferation and invasion while inhibited apoptosis, partly counteracted the function of carnosol in cells. Conclusion: Carnosol might induce cell apoptosis and inhibits invasion and proliferation in skin epidermoid cancer in vitro through MMP11-EGFR pathway.

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Skin Reaction to Cetuximab as a Criterion for Treatment Selection in Head and Neck Cancer

Abstract: Rate of serious CMb-induced hypersensitivity reactions was unacceptably high. Even though immunoradiotherapy was administered only to the prognostically most favorable group of patients, it resulted in no advantage over chemoradiotherapy.

Cited by 5 publications

References 27 publications

Outcome of patients with recurrent/metastatic squamous cell head and neck cancer treated with platinum‑based chemotherapy with or without cetuximab in real‑world practice

Outcome of patients with recurrent/metastatic squamous cell head and neck cancer treated with platinum‑based chemotherapy with or without cetuximab in real‑world practice

Comparative efficacy and safety of radiotherapy/cetuximabversusradiotherapy/chemotherapy for locally advanced head and neck squamous cell carcinoma patients: a systematic review of published, primarily non-randomized, data

Carnosol Induces Cell Apoptosis and Inhibits Invasion and Proliferation in Skin Epidermoid Cancer in Vitro Through MMP11-EGFR Pathway

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