A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85

Overgaard, Jens; Hansen, Hanne Sand; Overgaard, Marie; Bastholt, Lars; Berthelsen, A; Specht, Lena; Lindeløv, B.; Jørgensen, Karsten

doi:10.1016/s0167-8140(97)00220-x

Cited by 516 publications

(290 citation statements)

References 41 publications

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“…These schemes can be combined as in the CHART study randomizing 918 patients with head and neck carcinomas (34). The addition of a chemical hypoxic cell radiosensitizer such as nimorazole also improved the prognosis for patients with pharyngeal tumours (15).…”

Section: Discussionmentioning

confidence: 99%

“…a 3-week gap after the rst part of the treatment; 9 patients scheduled for this strategy did not complete the treatment. Forty-ve patients received a chemical radiosensitizer, either misonidazole or nimorazole, as a part of the randomized trials DAHANCA 2 (14) and DAHANCA 5 (15). Nine patients were included in the DAHANCA I phase II study of the effect of administration of bleomycin, methotrexate and vincristine before irradiation (16).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Squamous Cell Carcinoma of the Oropharynx-An Analysis of Treatment Results in 289 Consecutive Patients

Johansen

Grau²,

Overgaard

2000

Acta Oncologica

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Squamous Cell Carcinoma of the Oropharynx-An Analysis of Treatment Results in 289 Consecutive Patients

Johansen

Grau²,

Overgaard

2000

Acta Oncologica

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“…Of these drugs, misonidazole, a 2-nitroimidazole, showed remarkable results in laboratory studies (Sheldon et al, 1974;Brown, 1975), but the clinical experience was disappointing because of dose limitations due to high neurotoxicity (Dische, 1985). New nitroimidazole compounds were then developed, and the 5-nitroimidazole nimorazole was reported to significantly improve the effect of radiotherapy in some head and neck cancers, with only mild associated toxicity (Overgaard et al, 1998).…”

Section: How To Overcome Tumor Hypoxiamentioning

confidence: 99%

How to overcome (and exploit) tumor hypoxia for targeted gene therapy

Greco

Marples

Joiner

et al. 2003

Journal Cellular Physiology

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Tumor hypoxia has long been recognized as a critical issue in oncology. Resistance of hypoxic areas has been shown to affect treatment outcome after radiation, chemotherapy, and surgery in a number of tumor sites. Two main strategies to overcome tumor hypoxia are to increase the delivery of oxygen (or oxygen-mimetic drugs), or to exploit this unique environmental condition of solid tumors for targeted therapy. The first strategy includes hyperbaric oxygen breathing, the administration of carbogen and nicotinamide, and the delivery of chemical radiosensitizers. In contrast, bioreductive drugs and hypoxia-targeted suicide gene therapy aim at activating cytotoxic agents at the tumor site, while sparing normal tissue from damage. The cellular machinery responds to hypoxia by activating the expression of genes involved in angiogenesis, anaerobic metabolism, vascular permeability, and inflammation. In most cases, transcription is initiated by the binding of the transcription factor hypoxia-inducible factor (HIF) to hypoxia responsive elements (HREs). Hypoxia-targeting for gene therapy has been achieved by utilizing promoters containing HREs, to induce selective and efficient transgene activation at the tumor site. Hypoxia-targeted delivery and prodrug activation may add additional levels of selectivity to the treatment. In this article, the latest developments of cancer gene therapy of the hypoxic environment are discussed, with particular attention to combined protocols with ionizing radiation. Ultimately, it is proposed that by adopting specific transgene activation and molecular amplification systems, resistant hypoxic tumor tissues may be effectively targeted with gene therapy.

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“…Thirtyve patients were treated with split-course radiotherapy. Twenty-seven patients received a hypoxic radiosensitizer, either misonidazole or nimorazole as a part of the randomized trials DAHANCA 2 (13) and DAHANCA 5 (14). Three patients were included in the DAHANCA 1 study of induction chemotherapy by administration of bleomycin, methotrexate and vincristine, followed by irradiation (15).…”

Section: Methodsmentioning

confidence: 99%

Squamous Cell Carcinoma of the Nasopharynx&An Analysis of Treatment Results in 149 Consecuti v e Patients

Johansen

Grau²,

Overgaard³

2001

Acta Oncologica

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A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85

Cited by 516 publications

References 41 publications

Squamous Cell Carcinoma of the Oropharynx-An Analysis of Treatment Results in 289 Consecutive Patients

Squamous Cell Carcinoma of the Oropharynx-An Analysis of Treatment Results in 289 Consecutive Patients

How to overcome (and exploit) tumor hypoxia for targeted gene therapy

Squamous Cell Carcinoma of the Nasopharynx&An Analysis of Treatment Results in 149 Consecuti v e Patients

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