ARCON: experience in 215 patients with advanced head and neck cancer

Kaanders, J.H.; Pop, L.A.; Marres, H.A.; Bruaset, I.; Hoogen, F.J. van den; Merkx, Matthias A.W.; Kogel, A.J. van der

doi:10.1016/s0360-3016(01)01978-2

Cited by 55 publications

(65 citation statements)

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“…In clinical studies, the treatment was given in combination with standard or accelerated radiotherapy (ARCON). Phase I, II, and III trials indicated feasibility and some therapeutic efficacy, in particular in the treatment of bladder and head and neck carcinoma, albeit limited by the gastro-intestinal toxicity of nicotinamide (Hoskin et al, 1997(Hoskin et al, , 1999Miralbell et al, 1999;Bernier et al, 2000;Kaanders et al, 2002).…”

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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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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“…In that series of 346 patients, tumor stage was 1 of 2 most significant covariates for survival. 13 Based on the favorable treatment outcomes seen with ARCON in patients with head and neck carcinoma 9,11 and in our series, morbidity, tumor response, and patient survival were acceptable. Currently, a Phase III, randomized, multicenter trial of carbogen and nicotinamide funded by Cancer Research-UK is underway.…”

Section: Discussionmentioning

confidence: 63%

“…8,9 In our center, historic comparisons showed no increase in the severity of normal tissue reactions in 35 patients with advanced head and neck tumors who received treatment with ARCON, 10 and these observations were confirmed in a larger Dutch series. 9,11 However, treatment of bladder carcinoma results in unavoidable irradiation of both normal bladder and bowel, and an important prerequisite for the successful clinical application of ARCON is that any increase in tumor-cell kill is not paralleled by a corresponding enhancement of normal tissue damage. Bowel is of particular concern, because it was one of the structures associated with a significant increase in radiation morbidity in the clinical trials of HBO.…”

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confidence: 99%

Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide

Hoskin

Rojas

Phillips

et al. 2005

Cancer

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BACKGROUND Accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in Phase II studies of patients with advanced head and neck and bladder carcinomas. Thus, morbidity and treatment outcomes from the latter study were analyzed to evaluate the therapeutic potential of ARCON. METHODS Acute and late morbidity was assessed in 105 patients with high‐grade superficial or muscle‐invasive bladder carcinoma who were given accelerated radiotherapy (50–55 grays in 4 weeks) with carbogen alone or with ARCON. Urinary dysfunction was scored based on daytime frequency, nocturia, incontinence, dysuria, hematuria, and urgency. Bowel morbidity was based on stool frequency and consistency, rectal discharge, blood loss, and medication. Endpoints for treatment outcome were overall survival, disease‐free survival, and locoregional control. RESULTS Nearly all patients experienced reduced ability to retain urine beyond 2 hours, although 20–30% had almost normal function at night. Incidence of acute moderate or worse dysuria was 41% with ARCON and 56% with carbogen; 96% and 76% of patients, respectively, had bowel frequencies ≥ 3 times per day. By 10–12 weeks from the start of radiotherapy, acute reactions returned to baseline levels. At 3 years, the daytime frequency ≤ 2 times per hour was ≈ 75% in both arms. Incidence of severe hematuria (≤ 25%) and urinary urgency (≤ 16%) was much lower. No more than 6% of patients had severe bowel morbidity. With most assays, the differences between schedules were not significant either for acute or late morbidity. Local tumor control and survival rates at 3 years were 53% and 43%, respectively, for ARCON, similar to the rates for carbogen alone. CONCLUSIONS Historical comparisons suggested no overt increase in normal tissue radiosensitivity when adding carbogen and nicotinamide. Although, for some endpoints, the incidence of late sequelae was higher than expected, overall morbidity was no worse than reported by others. The data indicated that ARCON could achieve a therapeutic gain in patients with advanced bladder carcinoma. A Phase III, randomized, multicenter trial is underway currently in the United Kingdom to evaluate these findings. Cancer 2005. © 2005 American Cancer Society.

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“…[20][21][22][23][24][25] For example, it has been reported that ARCON therapy for head and neck cancer increased early skin and mucosal reactions. [20][21][22][23] It has also been reported that carbogen plus nicotinamide or ARCON therapy of gliomas increased early toxicity of the central nervous system. [24,25] In other words, increased oxygenation during RT increases side effects, as hyperoxygenation of non-malignant cells may increase impression by RT.…”

Section: Discussionmentioning

confidence: 99%

Effect of Radiotherapy Dose Rates on Early Intestinal Toxicity

Ünal¹

2016

TJ Oncol

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OBJECTIVEThe aim of the present study was to investigate early histopathological changes in small intestinal tissue caused by radiotherapy (RT) applications with varying dose rates in rats. METHODSThirty rats were divided into 3 groups. The first and second groups were irradiated at 300 MU/min and 600 MU/min, respectively. The third was a control group. On day 7 following RT application, small intestine tissue samples were obtained. RESULTSMucosal thickness was significantly lower in the 300 MU/min group, compared to the other groups, and thickness was significantly lower in the 600 MU/min group, compared to the control group. Villus length was significantly decreased in the 300 MU/min group, compared to the other groups, and villus width was significantly increased in the control group, compared to the other groups. CONCLUSIONRT application with high dose may be less toxic for tissue with high risk for acute toxicity, such as that of the small intestine.

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ARCON: experience in 215 patients with advanced head and neck cancer

Cited by 55 publications

References 0 publications

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

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

Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide

Effect of Radiotherapy Dose Rates on Early Intestinal Toxicity

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