Prevention of Second Primary Tumors with Isotretinoin in Squamous-Cell Carcinoma of the Head and Neck

Hong, Waun Ki; Lippman, Scott M.; Itri, Loretta M.; Karp, Daniel D.; Lee, Jin S.; Byers, Robert M.; Schantz, Stimson P.; Kramer, Alan M.; Lotan, Reuben; Peters, Lester J.; Dimery, Isaiah W.; Brown, Barry W.; Goepfert, Helmuth

doi:10.1056/nejm199009203231205

Cited by 1,185 publications

(513 citation statements)

References 34 publications

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“…The first goal of our cancer chemoprevention trials was to define a dose of DFMO that was both safe and effective. Our dose de-escalation studies and subsequent randomized placebo-controlled studies demonstrated that oral doses of DFMO between 0.25 and 0.5 g/m 2 /day for times as short as 1 month and as long as 1 year were effective in reducing rectal polyamine content in humans [85][86][87] . These studies also demonstrated that these doses, which can reduce rectal polyamine levels, did not produce detectable toxicities in excess of those observed in the group receiving placebo.…”

Section: Box 3 | Measuring Polyamine Variables In Clinical Studiesmentioning

confidence: 71%

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Polyamines and cancer: old molecules, new understanding

2004

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| The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues. UREA CYCLEThe key metabolic pathway in mammals for eliminating cellular breakdown products containing nitrogen. NATURE REVIEWS | CANCER VOLUME 4 | OCTOBER 2004 | 7 8 1

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Section: Box 3 | Measuring Polyamine Variables In Clinical Studiesmentioning

confidence: 71%

“…'Proof of principle' for chemoprevention of cancer in humans has been established [85][86][87] . However, toxicity has abrogated the widespread adoption of agents, such as retinoids, for the prevention of cervical and oral cancers 89 .…”

Section: Implications and Future Directionsmentioning

confidence: 99%

Polyamines and cancer: old molecules, new understanding

2004

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“…It is well known that squamous cell carcinoma of the lower lip, is more curable than those of the oral cavity or the larynx, 32 and the major problem for this malignancy is local recurrence after surgical removal of the primary tumor. On the other hand, squamous cell carcinoma of the oral cavity and larynx are more aggressive.…”

Section: Survival and Recurrence Analysismentioning

confidence: 99%

Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

et al. 2005

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Vascular endothelial growth factor is a peptide with well-defined actions on the vasculature and fundamental role in tumor angiogenesis. Its action in vascular endothelium is exerted in a paracrine manner. The immunohistochemical expression of this protein by cancer cells in head and neck squamous cell carcinoma was correlated with increased tumor aggressiveness and poor survival in previous studies. In the past years, an increasing amount of studies demonstrated potential autocrine action of vascular endothelial growth factor in various neoplasms. However, the existence and the impact of such autocrine action in head and neck cancer have not been demonstrated yet. In this retrospective study, we evaluated the expression of vascular endothelial growth factor and its receptors in neoplastic cells, in a cohort of patients with head and neck squamous cell carcinoma, and compared this expression with tumor aggressiveness, clinicopathologic parameters and outcome. High expression of vascular endothelial growth factor was strongly correlated with high expression of vascular endothelial growth factor receptor-2 (but not vascular endothelial growth factor receptor-1) on the cancer cells (Po0.001). The co-overexpression of both the protein and vascular endothelial growth factor receptor-2 was associated with higher tumor proliferation rate (Po0.001). The above cooverexpression also correlated with worse survival (log rank Po0.05) in patients with oral-larynx squamous cell carcinoma. Our results suggest that an autocrine vascular endothelial growth factor loop, mediated via vascular endothelial growth factor receptor-2, probably exists in head and neck squamous cell carcinoma. These observations support the hypothesis that the use of vascular endothelial growth factor receptor-2 inhibitors as adjuvant antiangiogenic therapy might have beneficial effects for these patients, by disrupting both paracrine (endothelial-dependent) and autocrine actions of vascular endothelial growth factor.

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“…50 Hong's group found that patients treated with 13-cRA for 12 months had a decrease in second primary tumors in the lung and upper aerodigestive tract (24% in the control group, 4% in the treated group) after 32 months (P = 0.005). 50,51 After 55 months of follow-up, the results were still favorable for the treatment arm (7% vs 33%, p = 0.008). Because the study included mostly patients with advanced stage III or IV disease, they were unable to demonstrate a survival benefit.…”

Section: Retinoidsmentioning

confidence: 99%

Chemoprevention of Head and Neck Cancer

Armstrong

Meyskens

2000

Otolaryngol.--head neck surg.

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728Increasing emphasis has been placed on chemoprevention as understanding of the genetic and molecular events of carcinogenesis has evolved. More than 1000 compounds that inhibit cancer development in vitro or in animal models have been identified, and active research is under way to determine which of these agents will be both effective and nontoxic in human beings. Currently, 13-cis-retinoic acid is the most studied chemopreventive agent against head and neck cancers. Unfortunately, this vitamin A derivative has significant clinical toxicity, which limits its utility in a practice setting. The efficacy of the retinoids, however, has stimulated efforts to find other chemopreventive compounds that are both effective and nontoxic. This review discusses head and neck premalignancy, chemoprevention strategies, retinoids, and several other classes of chemopreventive agents with potential efficacy against head and neck premalignancy.

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Prevention of Second Primary Tumors with Isotretinoin in Squamous-Cell Carcinoma of the Head and Neck

Abstract: Daily treatment with high doses of isotretinoin is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck, although it does not prevent recurrences of the original tumor.

Cited by 1,185 publications

References 34 publications

Polyamines and cancer: old molecules, new understanding

Polyamines and cancer: old molecules, new understanding

Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

Chemoprevention of Head and Neck Cancer

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