Adjuvant therapy for high‐risk primary and resected metastatic melanoma

Hersey, Peter

doi:10.1046/j.1445-5994.2002.00289.x

Cited by 31 publications

(17 citation statements)

References 48 publications

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“…Although early localized melanoma is curable with surgical excision (3), the median survival time for patients with metastatic melanoma is 6 to 10 months (4). Treatment for the advanced disease is ineffective despite combined therapeutic regimes of surgery, immunotherapy, radiotherapy, and chemotherapy (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Nuclear Factor-κB p105/p50 in Human Melanoma and Its Role in Cell Migration

Gao

Dai²,

Martinka³

et al. 2006

Cancer Research

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Transcriptional factor nuclear factor-KB (NF-KB) family has been shown to play an important role in tumor pathogenesis and serve as a potential target in cancer therapy. However, it is necessary to clarify the specific functions of NF-KB members, which would provide the basis for the selective blockade and reduction of therapeutic side effects resulting from unspecific inhibition of NF-KB members. In this study, we explored the role of NF-KB p105/p50 in melanoma pathogenesis in vitro and in vivo. We found that the expression of NF-KB p105/p50 significantly increased in dysplastic nevi, primary melanoma, and metastatic melanoma compared with normal nevi (P = 0.0004, C 2 test). Furthermore, NF-KB p105/ p50 nuclear staining increased with melanoma progression and strong NF-KB p105/p50 nuclear staining was inversely correlated with disease-specific 5-year survival of patients with tumor thickness >2.0 mm (P = 0.014, log-rank test). Multivariate Cox regression analysis revealed that nuclear expression of NF-KB p105/p50 is an independent prognostic factor in this subgroup. Moreover, we found that upregulation of NF-KB p50 enhanced melanoma cell migration, whereas small interfering RNA knockdown inhibited cell migration. In addition, overexpression of NF-KB p50 induced RhoA activity and Rock-mediated formation of stress fiber in melanoma cells. Taken together, our data indicate that NF-KB p105/p50 may be an important marker for human melanoma progression and prognosis as well as a potentially selective therapeutic target. (Cancer Res 2006; 66(17): 8382-8)

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Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Nuclear Factor-κB p105/p50 in Human Melanoma and Its Role in Cell Migration

Gao

Dai²,

Martinka³

et al. 2006

Cancer Research

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“…Although the perceived ''melanoma epidemic'' largely represents increased detection of thin melanomas (2), melanoma affects predominantly younger age groups and results in a loss of productive life years exceeded only by childhood malignancies and testicular cancer (3,4). Melanoma is largely unresponsive to cytotoxic chemotherapy (5), biological agents (6,7), and various vaccination strategies (8). A small subgroup of patients seems to benefit from biological and/or cytotoxic chemotherapies, but identifying these patients a priori is currently not possible, which necessitates the exposure of many patients to substantial toxicities with a low probability of benefit.…”

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confidence: 99%

Predicting Clinical Outcome through Molecular Profiling in Stage III Melanoma

John

Black

Toro³

et al. 2008

Clinical Cancer Research

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Purpose: Patients with macroscopic stage III melanoma represent a heterogeneous cohort with average 5-year overall survival rates of <30%. With current algorithms, it is not possible to predict which patients will achieve longer-term survival. We hypothesized that molecular profiling could be used to identify prognostic groups within patients with stage III melanoma while also providing a greater understanding of the biological programs underpinning these differences. Experimental Design: Lymph node sections from 29 patients with stage IIIB and IIIC melanoma, with divergent clinical outcome including 16 ''poor-prognosis'' and 13 ''good-prognosis'' patients as defined by time to tumor progression, were subjected to molecular profiling using oligonucleotide arrays as an initial training set. Twenty-one differentially expressed genes were validated using quantitative PCR and the 15 genes with strongest cross-platform correlation were used to develop two predictive scores, which were applied to two independent validation sets of 10 and 14 stage III tumor samples. Results: Supervised analysis using differentially expressed genes was able to differentiate the prognostic groups in the training set. The developed predictive scores correlated directly with clinical outcome.When the predictive scores were applied to the two independent validation sets, clinical outcome was accurately predicted in 90% and 85% of patients, respectively. Conclusion: We describe a gene expression profile that is capable of distinguishing clinical outcomes in a previously homogeneous group of stage III melanoma patients.

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“…Prolongation of overall survival in patients with moderate and high risk has been demonstrated in studies evaluating high-dose IFN␣ treatment. 6,[12][13][14]41 However, although high-dose IFN␣ treatment regimens are widely used in the United States and, according to some, should be the gold standard of adjuvant therapy, 4,40 the high cost of high-dose IFN␣ treatment, the toxicity profile (leading in some cases to the death of disease-free patients), 42,43 and conflicting efficacy results have created a dilemma for dermatologists and oncologists practicing in Europe. Consequently, low-and intermediate-dose IFN␣ regimens are still under consideration in Europe.…”

Section: Discussionmentioning

confidence: 99%

“…6,10,11,14,39,40 IFN␣ is the drug most frequently prescribed for adjuvant treatment of melanoma, but currently there is no consensus on the optimal regimen. Prolongation of overall survival in patients with moderate and high risk has been demonstrated in studies evaluating high-dose IFN␣ treatment.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] Treatment with interferon alfa (IFN␣) has been shown to prolong disease-free survival in melanoma patients at moderate to high risk of developing metastatic disease after surgery (American Joint Committee on Cancer [AJCC] stage IIA to III) 5 and in some studies, to prolong overall survival in this patient population. [6][7][8][9][10][11][12][13][14] As derivates of vitamin A, retinoids also show a wide spectrum of biologic activities, including immune modulation, sebosuppression, and effects on cell proliferation and cell differentiation in both melanoma and nonmelanoma cell lines. [15][16][17][18][19] In some clinical trials evaluating isotretinoin and etretinate for treatment of nonmelanoma skin cancers, tumor suppression was achieved, 18,20 although isotretinoin was ineffective in preventing basal cell carcinomas in a large study with 981 patients.…”

Section: Introductionmentioning

confidence: 99%

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Prospective, Randomized, Multicenter, Double-Blind Placebo-Controlled Trial Comparing Adjuvant Interferon Alfa and Isotretinoin With Interferon Alfa Alone in Stage IIA and IIB Melanoma: European Cooperative Adjuvant Melanoma Treatment Study Group

Richtig

Soyer

Posch

et al. 2005

JCO

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A B S T R A C T PurposeThe combination of interferon alfa (IFN␣) and isotretinoin has shown a direct antiproliferative effect on human melanoma cell lines, but it remained unclear whether this combination is more effective than IFN␣ alone in patients with metastatic melanoma. We evaluated safety and efficacy of IFN␣ and isotretinoin compared with IFN␣ alone as adjuvant treatment in patients with primary malignant melanoma stage IIA and IIB. Patients and MethodsIn a prospective, randomized, double-blind, placebo-controlled trial, 407 melanoma patients in stage IIA (301 patients) and IIB (106 patients) were randomly assigned to either IFN␣ and isotretinoin (isotretinoin group; 206 patients) or IFN␣ and placebo (placebo group; 201 patients) after excision of the primary tumor. IFN␣ was administered three times a week at a dose of 3 million units subcutaneously for 24 months. Isotretinoin at a dose of 20 mg for patients Յ 73 kg, 30 mg for patients greater than 73 kg, or placebo daily for 24 months. ResultsA scheduled interim analysis revealed no significant differences in survival rates, with the isotretinoin group and the placebo group showing 5-year disease-free survival rates of 55% (95% CI, 46% to 65%) and 67% (95% CI, 59% to 75%), respectively, and overall 5-year survival rates of 76% (95% CI, 67% to 84%) and 81% (95% CI, 74% to 88%), respectively. The trial was stopped for futility. ConclusionThe addition of isotretinoin to an adjuvant treatment of low-dose IFN␣ in patients with stage IIA and IIB melanoma had no significant effect on disease-free or overall survival and is therefore not recommended.

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Adjuvant therapy for high‐risk primary and resected metastatic melanoma

Cited by 31 publications

References 48 publications

Prognostic Significance of Nuclear Factor-κB p105/p50 in Human Melanoma and Its Role in Cell Migration

Prognostic Significance of Nuclear Factor-κB p105/p50 in Human Melanoma and Its Role in Cell Migration

Predicting Clinical Outcome through Molecular Profiling in Stage III Melanoma

Prospective, Randomized, Multicenter, Double-Blind Placebo-Controlled Trial Comparing Adjuvant Interferon Alfa and Isotretinoin With Interferon Alfa Alone in Stage IIA and IIB Melanoma: European Cooperative Adjuvant Melanoma Treatment Study Group

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