Nimoral (nimorazole) / Norgine, Hikma - LARVOL DELTA

Compliance to national guidelines for head and neck cancer patients with nodal involvement treated with curative radiotherapy and weekly cisplatin (ESTRO 2026) - "Material/ Consecutive patients with HNSCC (oral cavity, larynx and pharynx (nasopharynx excluded) between 2014- 2022 were prospectively registered in the local DAHANCA database covering a region of 1.4 million inhabitants.National DAHANCA guidelines recommend concomitant chemo-radiotherapy with cisplatin 40mg/m2; 66-68Gy/33-34Fx; 6 fx/week or 76Gy/56fx BID, 10fx/week and the hypoxic radiosensitizer, nimorazole to patients with node-positive HNSCC. In this group treated according to national guidelines, compliance to cisplatin was overall good across different tumour locations, tumour stage, sex, age and co-morbidities and performance status, without compromising the radiotherapy treatment and overall treatment time. It calls for a less selective approach to concomitant weekly cisplatin.Table 1 Figure 1"

Clinical • Compliance • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Incidence and survival of supraglottic squamous cell carcinoma in Denmark, 1986-2020: a national population-based DAHANCA study of 3154 patients (ESTRO 2026) - "From conventional RT (66- 68Gy/33-34fx/5fx per week) stepwise refinements have been implemented through national clinical trials, introducing the hypoxic sensitizer nimorazole (N), accelerated RT (ART:66-68Gy/33-34fx/6fx per week), hyperfractionated RT (HART:76Gy/56fx/10fx per week), and concurrent cisplatin chemotherapy (C). The incidence of SGLSCC in Denmark declined markedly from 1986-2020, accompanied by significant gains in survival. These improvements reflect the stepwise implementation of evidence-based treatment guidelines developed through DAHANCA, including nimorazole, accelerated and hyperfractionated RT, and concurrent chemotherapy."

Clinical • Head and Neck Cancer • Laryngeal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Supraglottic Laryngeal Cancer

DAHANCA30: DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC. (clinicaltrials.gov) - P3 | N=1252 | Recruiting | Sponsor: Danish Head and Neck Cancer Group | Trial completion date: Dec 2019 ➔ Dec 2023 | Trial primary completion date: Dec 2019 ➔ Dec 2023

Head-to-Head • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

DAHANCA30: DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC. (clinicaltrials.gov) - P3 | N=1262 | Recruiting | Sponsor: Danish Head and Neck Cancer Group | Not yet recruiting ➔ Recruiting | Initiation date: Jan 2016 ➔ Sep 2016

Enrollment open • Head-to-Head • Trial initiation date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

DAHANCA30: DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC. (clinicaltrials.gov) - P3 | N=1262 | Not yet recruiting | Sponsor: Danish Head and Neck Cancer Group

Head-to-Head • New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

QoLATI: Quality of Life After Primary TORS vs IMRT for Patients With Early-stage Oropharyngeal Squamous Cell Carcinoma (clinicaltrials.gov) - P=N/A | N=138 | Active, not recruiting | Sponsor: Christian von Buchwald | Trial completion date: Jan 2029 ➔ Dec 2029

HEOR • Trial completion date • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

An international placebo-controlled randomized multicenter trial of nimorazole with accelerated chemo-radiotherapy for locally advanced HPV-negative squamous cell carcinoma of the head and neck (HNSCC). (PubMed, Radiother Oncol) - "NIM improved locoregional control in advanced HPV-negative HNSCC, but without significant survival improvement. This finding underscore that hypoxic radiosensitization plays a role in chemo-radiotherapy for HNSCC. The incompleteness of the study precluded further detailed analysis."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Radiotherapy quality assurance of the prospective randomised EORTC-1219/DAHANCA-29 trial: an individual case review analysis. (PubMed, Radiother Oncol) - "P-ICR significantly improved CTV delineation quality, ensuring higher protocol compliance and treatment planning accuracy. p-ICRs are recommended for complex treatments, tailored to the performance of individual sites."

Journal • Head and Neck Cancer • Oncology • Solid Tumor

Impact of GTV-CTV margin and other predictors on radiation-induced dysphagia in head and neck cancer patients from DAHANCA group. (PubMed, Acta Oncol) - "Radiation dose to the oral cavity and lower PCM were the strongest modifiable predictors of dysphagia risk. Margin size was not independently associated, possibly due to confounding by clinical judgement."

Journal • Retrospective data • Gastrointestinal Disorder • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A case of toxic encephaloneuropathy during treatment with nimorazole (PubMed, Ugeskr Laeger) - "No cases of nimorazole-induced neurotoxicity like Metronidazole encephalopathy have been published. In this case, we report a patient who developed toxic encephaloneuropathy during nimorazole radiosensitisation."

Journal • CNS Disorders • Epilepsy • Head and Neck Cancer • Infectious Disease • Oncology • Pain • Solid Tumor

A prospective randomized multicenter trial of Nimorazole as hypoxic modifier of accelerated chemo-radiotherapy for locally advanced HPV-neg HNSCC. (ESTRO 2025) - "Total Cisplatin dose was 200 mg/m2 either weekly (40 mg/m2 on week 1 to 5) or 3-weekly (100 mg/m2 on weeks 1 & 4). Despite the reduced patient number, NIM was found to improve locoregional control in advanced HPV-neg HNSCC, but without significant improvement in DSS or OS. This underlines that hypoxic modification is still active in concomitant chemo-radiotherapy of squamous cell carcinoma. The incompleteness of the study precludes analysis of the predictive value of the hypoxic-gene signature."

Clinical • Metastases • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

DAHANCA19: A randomized phase III study of primary curative (chemo)-radiotherapy and the EGFR-inhibitor zalutumumab for squamous cell carcinoma of the head and neck. (PubMed, Radiother Oncol) - "Addition of concomitant zalutumumab to primary (chemo-)radiotherapy and concomitant nimorazole for HNSCC did not increase locoregional control nor disease-specific or overall survival."

Journal • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

QoLATI: Quality of Life After Primary TORS vs IMRT for Patients With Early-stage Oropharyngeal Squamous Cell Carcinoma (clinicaltrials.gov) - P=N/A | N=138 | Active, not recruiting | Sponsor: Christian von Buchwald | Recruiting ➔ Active, not recruiting

Enrollment closed • HEOR • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Repurposing radiosensitising medicines for radiotherapy: an overview. (PubMed, BMJ Oncol) - "Two compounds, nicotinamide and nimorazole, have entered routine but limited clinical use in combination with radiotherapy...Upon reviewing the trials, we identified some common themes behind the unsuccessful efforts, including poor trial reporting, absence of biomarkers and patient selection, sub-optimal pharmacological properties, inappropriate trial design, lack or inadequate consideration of pre-clinical and clinical data, and limited funding support. We point out future directions to mitigate these issues and increase the likelihood of success in repurposing drug treatments for radiotherapy."

Journal • Review • Oncology

Evaluating deposited radiation energy amount and collision quantities of small-molecule radiosensitizers through Monte Carlo simulations. (PubMed, Heliyon) - "This study investigates the photon interaction mechanism of various small molecule radiosensitizers, including Hydrogen Peroxide, Nimorazole, 5-Fluorouracil, NVX-108, and others, using the MCNP 6.3 Monte Carlo simulation code. The study also examined the individual attenuation properties of these radiosensitizers against energetic photons, with NVX-108 showing the highest attenuation coefficient and a shorter mean free path, further supporting its superior potential in effective radiosensitization. It can be concluded that NVX-108 has higher interaction tendency with the energetic photons comparing other small-molecules under investigation."

Journal • Oncology

Transcriptomic and epigenetic landscape of nimorazole-enhanced radiochemotherapy in head and neck cancer. (PubMed, Radiother Oncol) - "In the present study, we found that nimorazole non-responder models were characterized by upregulation of genes involved in Retinol metabolism and xenobiotic metabolic process pathways, which might contribute to identify mechanisms of resistance to nitroimidazole compounds and potentially expand the repertoire of therapeutic options to treat HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

The effect of primary radiotherapy in oropharynx cancer: A phase IV population-based DAHANCA study (ESTRO 2024) - "These observations indicate that deintensification of treatment entails the risk of compromising patient outcome, as was also observed in three randomized trials substituting cisplatin with EGFR-inhibition in the treatment of p16-pos OPSCC (1-3)...In addition, all radiobiological modifications were found to be independently associated with better outcomes: hypoxic modification with nimorazole (LRF: 0.74 [0.59-0.92], DFS: 0.69 [0.58-0.81]), accelerated fractionated RT (LRF: 0.58 [0.40-0.83], DFS: HR: 0.67 [0.50-0.89]) and concurrent chemotherapy (LRF: 0.62 [0.51-0.76], DFS: HR: 0.54 [0.47-0.63]), Figure 2... Our findings represent real-life data obtained through application of a uniform, nationwide treatment strategy consisting of primary RT with radiobiological intensifications, in a national cohort of more than 3400 OPSCC patients. We observe acceptable outcomes in the overall cohort and confirm the favorable prognosis for patients with p16-positive disease...."

Clinical • P4 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma - A DAHANCA 19 study. (PubMed, Clin Transl Radiat Oncol) - "Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Optimizing Head and Neck Cancer Radiotherapy using '5+5 mm' DAHANCA Radiotherapy Guidelines (ICHNO 2024) - "Cox regression analysis indicated that factors such as sex (female), tumour site (HPV p16+ oropharyngeal), T stage (T1-2), treatment schedule (6 or 10 fractions per week), and the administration of nimorazole and chemotherapy were associated with superior three-year LC...Most recurrences occurred within CTV1 and were encompassed by the prescribed dose. A relevant next step could involve randomised trials comparing standard radiotherapy protocols with reduced margins and escalated doses to CTV1, further exploring the potential benefits of geometrically-based treatment strategies."

Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Tumor volume and cancer stem cell expression as prognostic markers for high-dose loco-regional failure in head and neck squamous cell carcinoma - a DAHANCA 19 study. (PubMed, Radiother Oncol) - "Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16+ OPSCC may contribute to better tumor control."

Biomarker • Cancer stem • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD44 • SLC3A2

Randomised phase III trial of the hypoxia modifier nimorazole added to radiotherapy with benefit assessed in hypoxic head and neck cancers determined using a gene signature (NIMRAD). (PubMed, Int J Radiat Oncol Biol Phys) - P3 | "Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve loco-regional control or survival."

Gene Signature • Journal • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Accelerated loss of lean body mass in head and neck cancer patients during cisplatin-based chemoradiation. (PubMed, Acta Oncol) - P=N/A | "48 patients (all tumor sites) received either 6 weeks of radiation alone (n = 16) with 66-68 Gy in 33-34 Fx, 5-6 Fx/week or CCRT, adding weekly cisplatin or carboplatin (n = 32)...Analyses adjusting for nimorazole, tumor stage, baseline BMI, mean radiation dose to constrictor muscles and oral cavity confirmed this...Patients receiving CCRT experienced significantly larger LBM loss than patients receiving radiation alone. Registered on clinincaltrials.gov (Identifier: NCT05890859)."

Journal • Head and Neck Cancer • Mucositis • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Prognostic biomarkers for the response to the radiosensitizer nimorazole combined with RCTx: a pre-clinical trial in HNSCC xenografts. (PubMed, J Transl Med) - "Nimorazole combined with RCTx improved local tumor control in some but not in all HNSCC xenografts. We identified prognostic biomarkers with the potential for translation to patients with HNSCC."

Journal • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Circinate Balanitis In Sexually Adquired Reactive Arthritis With Trichomonas Vaginalis Urethritis In Men (WCD 2023) - "In literature only two reports imply Trichomonas vaginalis association with RA, in both anti-inflammatory treatments failed to relieve symptoms but patients were cured with Antiparasitic treatment (nimorazole and metronidazole)...Urethral swab with Gram coloration is performed, evidencing in both cases the presence of Trichomonas vaginalis and in one case an association with Non-Gonococcal Infection. KEY MESSAGES: Circinate balanitis, Reiter’s syndrome, Sexually Acquired Reactive Arthritis, Trichomonas vaginalis"

Conjunctivitis • Dermatology • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • HLA-B

Radiation Therapies in Cancer. (PubMed, Cancer Treat Res) - "Specific chemotherapies are combined with radiation in the treatment of cancer after proper preclinical assessment of their effectiveness. Some classes of compounds include platinum-based drugs, antimicrotubules, antimetabolites (5-Fluorouracil, Capecitabine, Gemcitabine, Pemetrexed), topoisomerase I inhibitors, alkylating agents (Temozolomide), and other agents (Mitomycin-C, Hypoxic Sensitizers, Nimorazole)."

Journal • Oncology