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High-Performance Liquid Chromatography
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Joel J. Kirschbaum, Adorjan Aszalos
Nimorazole, which is structurally related to metronidazole, was assayed in blood using an octadecylsilane column with a mobile phase of methanol-water (30:70) containing 5 mM heptane sulfonic acid per liter and adjusted to pH 3.2 with acetic acid. The flow rate was 2 ml/min, and detection was at 313 nm [459]. As little as 5 μl of blood could be analyzed by this method. Between 5 and 1000 μg/ml the extraction efficiency was 100%. The lower limit of sensitivity was 5 ng.
The oxygen effect and therapeutic approaches to tumour hypoxia
Published in Michael C. Joiner, Albert J. van der Kogel, Basic Clinical Radiobiology, 2018
Michael R. Horsman, J. Martin Brown, Albert J. van der Kogel, Bradly G. Wouters, Jens Overgaard
In Denmark, an alternative strategy was taken that involved searching for a less toxic drug and thus nimorazole was chosen. Although its sensitizing ability was less than could theoretically be achieved by misonidazole or etanidazole, nimorazole was far less toxic and thus could be given in much higher doses. At a clinically relevant dose the SER was approximately 1.3. Furthermore, the drug could be given in association with a conventional radiation therapy schedule and was therefore amenable to clinical use. When given to patients with supraglottic and pharyngeal carcinomas (DAHANCA 5) a highly significant benefit in terms of improved locoregional tumour control and disease-free survival were obtained (34). These results are shown in Figure 17.7c and d and are consistent with the earlier DAHANCA 2 study for misonidazole. As a consequence, nimorazole has now become part of the standard treatment schedule for head and neck tumours in Denmark.
Principles of Chemotherapy
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
It is known that tumour cell hypoxia induces radio-resistance, and there has been renewed interest in giving hypoxic cell radio-sensitizing drugs during radiotherapy. The two most common in use are the anti-helminthic drug nimorazole, which is extensively used in some parts of Europe, and tirapazamine, an anticoagulant that is activated in hypoxic environments. Although established in some parts of the world, trials are ongoing with these agents to establish efficacy and with nimorazole, patient tolerability.
The management and survival outcomes of nasopharyngeal cancer in the Nordic countries*
Published in Acta Oncologica, 2018
A. Mäkitie, M. Ruuskanen, J. Bentzen, E. Brun, M. Gebre-Medhin, S. Friesland, E. Marsk, L. Hammarstedt-Nordenvall, E. Gille, J. Reizenstein, G. Adell, L. Farnebo, J. Rzepecki, H. Haugen, K. Söderström, B. Zackrisson, S. Bergström, B. Lödén, L. Cederblad, G. Laurell, E. Smeland, J. Folkvard Evensen, J. Å. Lund, H. Tøndel, Å. Karlsdottir, J. Jóhannsson, J. Johansen, C. A. Kristensen, K. Jensen, L. J. Andersen, P. Koivunen, M. Korpela, L. Voutilainen, T. Wigren, H. Minn, H. Joensuu, J. Overgaard, K. Saarilahti
A high (≥70 Gy), intermediate (65–69 Gy) and low cumulative dose (<65 Gy) of RT was given to 107 (31.2%), 183 (53.2%) and 43 (12.5%) patients, respectively (data missing for 11 patients). Seventeen (5%) patients had hyperfractionated treatment. Concurrent CT was given to 228 (66.3%) out of the 344 patients. Seventy-two (20.9%) patients received CRT with cisplatin 100 mg/m2 every third week, and 154 (44.8%) patients with cisplatin 40 mg/m2 once a week. Nimorazole combined with accelerated RT was administered to five patients at one centre.
A prospective, multicenter DAHANCA study of hyperfractionated, accelerated radiotherapy for head and neck squamous cell carcinoma
Published in Acta Oncologica, 2019
Mette Saksø, Elo Andersen, Jens Bentzen, Maria Andersen, Jørgen Johansen, Hanne Primdahl, Jens Overgaard, Jesper Grau Eriksen
The proportion of patients, who received the scheduled radiotherapy was 97%. The median treatment time was 40 days (range 19–48). Ten patients stopped treatment prematurely (Supplementary Table 1), and of these six patients discontinued before 60 Gy was given. Five patients (2%) died during or shortly after therapy, but no deaths were directly treatment related. Nimorazole was discontinued during treatment in 82 patients (28%), mainly due to gastrointestinal adverse effects [14].
DAHANCA 9 – a randomized multicenter study to compare accelerated normo-fractionated radiotherapy with accelerated hyperfractionated radiotherapy in patients with primary squamous cell carcinoma of the head and neck (HNSCC)
Published in Acta Oncologica, 2019
Jan Folkvard Evensen, Hanne Sand Hansen, Marie Overgaard, Jørgen Johansen, Lisbeth Juhler Andersen, Jens Overgaard
Nimorazole was administered in doses of 1, 2 g/m2 body surface in connection with the first daily fraction. If 2 fx were applied on the same day, the second dose was limited to 1 g (irrespective of body surface). Total dose was planned to be ∼36 g/m2 and not allowed to exceed 40 g/m2 or a total of 75 g. The drug was given 90 min prior to each radiation treatment as described elsewhere [5].