A trial of Ro 03-8799 (pimonidazole) in carcinoma of the uterine cervix: an interim report from the Medical Research Council Working Party on advanced carcinoma of the cervix

Dische, Stanley; Chassagne, D.; Hope-Stone, H. F.; Dawes, P. J. D.; Roberts, John; Yosef, Hma; Bey, P.; Horiot, J.C.; Jacobson, A.; Frankendal, B.; Gonzales, Dionisio; Nguyen, Tan Dat; Daly, N; Floch, O. Le; Newman, H; Vieiro, E.; Bennett, M.H.; Bichel, P.; Duvillard, P.; Cook, Penny A.; Everett, Vincent; Machin, David

doi:10.1016/0167-8140(93)90089-q

Cited by 54 publications

(23 citation statements)

References 11 publications

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“…The Gynecology Oncology Group compared hydroxyurea vs. misonidazole with no improvement in survival [38].The Medical Research Council Working Party on advanced carcinoma of the cervix ran another randomized trial with Ro 03-8799 (pimonidazole) as a hypoxic cell-sensitizer. They observed no bene®t by adding pimonidazole to radiotherapy, and a truly adverse effect of the drug was a possible cause of failure in this trial [7]. A new approach is the use of bio-reductive drugs, such as tirapazamine (SR-4233), which in contrast to misonidazole and pimonidazole, offers a selective way of killing those resistant hypoxic cells.…”

Section: New Approachesmentioning

confidence: 85%

A survey on staging and treatment in uterine cervical carcinoma in the Radiotherapy Cooperative Group of the European Organization for Research and Treatment of Cancer

Coucke

Maingon

Ciernik

et al. 2000

Radiotherapy and Oncology

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Background: The treatment outcome of advanced stage uterine cervical carcinoma remains unsatisfactory. In order to elaborate a novel trial within The Radiotherapy Cooperative Group (RCG) of the European Organization for Research and Treatment of Cancer (EORTC), we conducted a survey in 1997±1998 to determine the variability of pre-treatment assessment and treatment options. The variability of choosing surgery, de®ned radiation therapy techniques and chemotherapy are investigated, as well as the center's choices of future treatment strategies.Methods: Fifty two of 81 RCG centers from the RCG have participated in the survey. As one would expect, there is a large variation in the techniques used for pretreatment evaluation and treatment options. There is no`standard' for reporting acute and late side effects. Chemotherapy is used neither systematically nor uniformly, and some centers continue to use neadjuvant chemotherapy modalities.Results: Furthermore, the survey reveals that there is a strong demand for the reduction of overall treatment-time, for clinical investigation of novel combined modality treatment strategies, especially chemo±radiation therapy, and also for the use of new radiation sensitizers.Conclusion: We conclude that a more homogeneous approach to the pretreatment evaluation as well as treatment techniques is required in order to allow adequate quality control in any future trial of the RCG in the EORTC. q

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Section: New Approachesmentioning

confidence: 85%

A survey on staging and treatment in uterine cervical carcinoma in the Radiotherapy Cooperative Group of the European Organization for Research and Treatment of Cancer

Coucke

Maingon

Ciernik

et al. 2000

Radiotherapy and Oncology

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“…The first of these was a European trial with pimonidazole in uterine cervical cancer, but the preliminary results were disappointing [42]. Etanidazole was then tested in two other multicenter trials in head and neck cancer, but the results showed no benefit [43,44].…”

Section: Targeting Hypoxic Cellsmentioning

confidence: 99%

“…= not significant; RT = radiotherapy. The trials were the Medical Research Council (MRC) trial with pimonidazole (Pimo) [42], the International Atomic Energy Agency (IAEA) trial with sanazol (Sana) [45], the Danish Head and Neck Cancer (DAHANCA) trials with misonidazole (Miso) [41] and nimorazole (Nim) [31], the North American Radiation Therapy Oncology Group (RTOG) [43], the European Organisation for Research and Treatment of cancer (EORTC) [44] trials with etanidazole (Eta), and the Japanese trials with doranidazole (Dora) [46].…”

Section: Targeting Hypoxic Cellsmentioning

confidence: 99%

302 The impact of hypoxia and its modification on the outcome of radiotherapy

2004

Radiotherapy and Oncology

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Since the initial observations made at the beginning of the last century, it has been established that solid tumors contain regions of low oxygenation (hypoxia). Tumor cells can survive in these hypoxic conditions and are a major factor in tumor radioresistance. This significance has resulted in hypoxia becoming the most cited biological topic in translational radiation oncology. Identifying hypoxic cells in human tumors has become paramount, and the ability to do this has been improved by the help of new imaging techniques and the use of predictive gene profiles. Substantial data confirm the presence of hypoxia in many types of human tumors, although with considerable heterogeneity among individual tumors. Various approaches have been investigated for eliminating the hypoxic population. These include increasing oxygen availability, directly radiosensitizing or killing the hypoxic cells, indirectly affecting them by targeting the tumor vascular supply, increasing the radiation dose to this resistant population, or by using radiation with a high linear energy transfer, for which hypoxia is believed to be less of an issue. Many of these approaches have undergone controlled clinical trials during the last 50 years, and the results have shown that hypoxic radiation resistance can indeed be overcome. Thus, ample data exists to support a high level of evidence for the benefit of hypoxic modification. However, such hypoxic modification still has no impact on general clinical practice. In this review we summarize the biological rationale, and the current activities and trials, related to identifying and overcoming hypoxia in modern radiotherapy.

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“…Curative radiotherapy consisted of a combination of external beam treatment of the small pelvic and para-aortic nodes and intracavitary brachytherapy [4,51. The protocol for intracavitary brachytherapy consisted of introduction of three hollow metal tubes in the vagina and uterine cavity, assessment of the exact position of the tubes with X rays and connection of the tubes to the Nucletron Selectron afterloading machine.…”

Section: Cuse Historymentioning

confidence: 99%