Melanoma: Négrier S

Saiag P, Bosquet L, Guillot B, Verola O, Avril MF, Bailly C, Cupissol D, Dalac S, Danino A, Dréno B, Grob JJ, Leccia MT, Renaud-Vilmer C, Négrier S, Anonymous00110. · Hôpital Ambroise Paré, 92104 Boulogne, Université Versailles-Saint Quentin, France. · Eur J Dermatol. · Pubmed #17540641 links to  free full text

This publication has no abstract.

Négrier S, Saiag P, Guillot B, Verola O, Avril MF, Bailly C, Cupissol D, Dalac S, Danino A, Dreno B, Grob JJ, Leccia MT, Renaud-Vilmer C, Bosquet L, Anonymous00209, Anonymous00210, Anonymous00211, Anonymous00212, Anonymous00213, Anonymous00214, Anonymous00215, Anonymous00216. · Centre Léon-Bérard, Lyon. · Bull Cancer. · Pubmed #16714227 links to  free full text

Abstract: CONTEXT: The National French federation of comprehensive cancer centres (FNCLCC) and the French society of dermatology (SFD) initiated together the update of clinical practice guideline for the management of patients with cutaneous melanoma in collaboration with the French national cancer institute and with specialists from French public universities, general hospitals and private clinics. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. OBJECTIVES: To update SOR guidelines for the management of patients with cutaneous melanoma previously validated in 1998 and French melanoma consensus conference published by SFD and ANAES in 1995. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. RESULTS: This article is a summary version of the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concerned (1) The new AJCC-UICC classification (2) Excision margins (3) Sentinel node biopsy (4) Adjuvant treatments (5) Initial staging and follow up of operated patients.

Négrier S, Saiag P, Guillot B, Verola O, Avril MF, Bailly C, Cupissol D, Dalac S, Danino A, Dreno B, Grob JJ, Leccia MT, Renaud-Vilmer C, Bosquet L, Anonymous00273, Anonymous00274. · Centre Léon-Bérard, Lyon. · Ann Dermatol Venereol. · Pubmed #16521904 No free full text.

This publication has no abstract.

Négrier S, Fervers B, Bailly C, Beckendorf V, Cupissol D, Doré JF, Dorval T, Garbay JR, Vilmer C, Anonymous00212. · Centre Léon Bérard, Lyon, France. · Br J Cancer. · Pubmed #11355977 links to  free full text

This publication has no abstract.

Négrier S, Fervers B, Bailly C, Beckendorf V, Cupissol D, Doré JF, Dorval T, Garbay JR, Vilmer C. · No affiliation provided · Presse Med. · Pubmed #10923143 No free full text.

This publication has no abstract.

Négrier S, Fervers B, Bailly C, Beckendorf V, Cupissol D, Doré JF, Dorval T, Garbay JR, Vilmer C. · FNCLCC, Standards, Options, Recommandations, 101, rue de Tolbiac, 75654 Paris Cedex 13. · Bull Cancer. · Pubmed #10705288 links to  free full text

Abstract: CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of patients with cutaneous melanoma. METHODS: Data have been identified by literature search using Medline - until December 1998 - and the personal reference lists of the expert group. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the management of cutaneous melanoma (CM) are: 1) The primary prevention of melanoma is based on a reduction in exposure to ultraviolet rays (solar or artificial). 2) The diagnosis of CM requires the surgical removal and histological examination of the lesion (standard). 3) The pathological report must include the diagnosis of primary malignant melanoma, the maximum thickness of the tumour in millimeters (Breslow), the clearance of surgical margins, the level of invasion (Clark), the presence and extension of regression and the presence of any ulceration (standard). 4) The standard treatment of a primary melanoma without lymph node involvement is based on surgery that must ensure adequate margins depending on the thickness of the tumour (standard, level of evidence B). 5) After surgery of a stage I melanoma, there is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B, French Consensus Conference). 6) For a local recurrence without node involvement, in the absence of other metastases, surgical excision is the standard treatment. 7) In the case of metastatic regional lymph nodes, a complete regional lymphadenectomy is required. There is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B). The inclusion of these patients in controlled studies of immunotherapy is recommended. 8) There is no standard therapeutic strategy for metastatic melanoma. Conventional palliative treatment is chemotherapy with dacarbazine (level of evidence B). 9) Follow-up is based on physical examination (standard). Patient information must encourage self-surveillance. Clinical surveillance and self-detection are indicated in all cases throughout life (standard).

Neidhardt-Bérard EM, Négrier S. · Centre Léon-Bérard, 28, rue Laennec, Lyon 69008. · Rev Prat. · Pubmed #15496028 No free full text.

Abstract: Disseminated melanoma is an incurable disease whose prognosis has remained unchanged over the past 20 years. To date, no consensus treatment has emerged. No treatment strategy has proved superior to dacarbazine (Deticene) monochemotherapy that remains considered as the reference treatment for this disease. Both multidrug chemotherapy and biochemotherapy have provided disappointing results, with poorer quality of life and no survival benefit for the patients. Other treatment approaches, particularly immunotherapy, remain to be investigated in clinical trials.

Négrier S. · Département de cancérologie médicale, Centre Léon-Bérard, 69373 Lyon Cedex 08. · Bull Cancer. · Pubmed #10029702 links to  free full text

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van Baren N, Bonnet MC, Dréno B, Khammari A, Dorval T, Piperno-Neumann S, Liénard D, Speiser D, Marchand M, Brichard VG, Escudier B, Négrier S, Dietrich PY, Maraninchi D, Osanto S, Meyer RG, Ritter G, Moingeon P, Tartaglia J, van der Bruggen P, Coulie PG, Boon T. · Ludwig Institute for Cancer Research, 74 avenue Hippocrate, UCL7459, B-1200 Brussels, Belgium; e-mail: · J Clin Oncol. · Pubmed #16061912 No free full text.

Abstract: PURPOSE: To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3(168-176) and MAGE-1(161-169), which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs). MATERIALS AND METHODS: The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3(168-176) and MAGE-1(161-169) peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals. RESULTS: Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression. CONCLUSION: Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.

Autier P, Doré JF, Négrier S, Liénard D, Panizzon R, Lejeune FJ, Guggisberg D, Eggermont AM. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · J Natl Cancer Inst. · Pubmed #10433619 links to  free full text

Abstract: BACKGROUND: In epidemiologic studies, sunscreen use is associated with increased risk of cutaneous melanoma, basal cell skin cancer, and higher numbers of nevi. It has been proposed that sunscreens may encourage prolonged sun exposure because they delay sunburn occurrence. We examined whether, under habitual conditions of sunscreen use, the sun-protection factor (SPF) had an influence on sun-exposure duration. METHODS: Before the 1997 summer holidays, we randomly assigned 87 French and Swiss participants who were 18-24 years of age to receive an SPF 10 or an SPF 30 sunscreen. Neither medical personnel nor study participants were aware of their sunscreen assignment. Participants were asked to complete daily records of their sun exposure. To avoid influencing the recreational sun-exposure habits of the study participants, no recommendation was made about sun exposure or sun protection. Furthermore, participants were told that the trial end point was the number of pigmented skin lesions before and after the holidays. One subject was lost to follow-up. All statistical tests were two-sided. RESULTS: The SPF 10 (n = 44) and SPF 30 (n = 42) groups had equivalent mean holiday durations (19.4 days versus 20.2 days) and mean quantities of sunscreen used (72.3 g versus 71.6 g). The mean cumulative sun exposures for the two groups were 58.2 hours and 72.6 hours, respectively (P =.011). The mean daily durations of sunbathing were 2.6 and 3.1 hours, respectively (P =.0013), and, for outdoor activities, they were 3.6 and 3.8 hours, respectively (P =.62). There was no difference in sunburn experience between the two groups. CONCLUSIONS: Use of higher SPF sunscreen seems to increase the duration of recreational sun exposure of young white Europeans.

Dorval T, Négrier S, Chevreau C, Avril MF, Baume D, Cupissol D, Oskam R, de Peuter R, Vinke J, Herrera A, Escudier B. · French Cancer Centers' Immunotherapy Group, Institut Curie, Paris. · Cancer. · Pubmed #10091789 links to  free full text

Abstract: BACKGROUND: The objective of the current study was to evaluate the response rate, survival, and toxicity of treatment with cisplatin and high dose intravenous continuous infusion interleukin-2 (IL-2) with or without interferon-alpha-2a (IFN) in patients with metastatic melanoma. METHODS: One hundred and seventeen patients with metastatic melanoma randomly were assigned to receive cisplatin, 100 mg/m2, followed after a 3-day rest period by IL-2, 18 x 10(6) IU/m2, on Days 3-6 and Days 17-21 (Arm 1) or cisplatin and IL-2 using an identical schedule plus subcutaneous IFN, 9 x 10(6) U, 3 times a week during IL-2 administration (Arm 2). In the absence of disease progression or undue toxicity, the cycle could be repeated on Day 29. Patients who responded after two cycles eventually could receive a third cycle. One hundred and one patients were evaluable for toxicity and efficacy. RESULTS: On treatment Arm 1, 3 patients (6%) achieved a complete response (CR) and 5 patients (10%) achieved a partial response (PR) with a median response duration of 3.8 months for the CRs and 8.7 months for the PRs. On treatment Arm 2, 2 patients (3%) achieved a CR (durations of 5.9 and 33.1 months, respectively) and 11 patients (21%) a PR with a median response duration of 8.3 months. The median durations of overall survival were 10.4 months (range, 1.1-39.7+ months) and 10.9 months (range, 0.5-38.1+ months) for treatment Arms 1 and 2, respectively. The toxicity profile was consistent with the known side effects of this IL-2 intravenous regimen combined with cisplatin chemotherapy and IFN. Toxicity was more pronounced in treatment Arm 2 compared with treatment Arm 1. There were 2 and 4 patients, respectively, in treatment Arms 1 and 2 who died within 28 days after completion of treatment. CONCLUSIONS: The observed overall response rates of 16% and 25% in treatment Arms 1 and 2, respectively, is lower than that expected with biochemotherapy; despite the fact that the objective of the trial was not to show any difference between the 2 treatment arms, our results indicate that the addition of IFN, at the dose and schedule used in this trial, fails to improve the activity of a cisplatin/IL-2 regimen significantly in patients with metastatic melanoma. Although response rates were relatively low, the median overall survival was nearly 1 year in both groups.

Rivoire M, Kodjikian L, Baldo S, Kaemmerlen P, Négrier S, Grange JD. · Department of Surgery, Centre Léon Bérard, 28 Rue Laennec, 69373 Lyon Cedex 08, France. · Ann Surg Oncol. · Pubmed #15886904 No free full text.

Abstract: BACKGROUND: Uveal melanoma patients with liver metastases have a poor prognosis. The effect of screening and multimodality treatment (including surgery) should be evaluated. METHODS: A total of 602 patients treated for uveal melanoma during a 14-year period had abdominal ultrasonography screening every 6 months. Sixty-three developed liver metastases as the first extraocular metastatic site. When possible, liver surgery and intra-arterial catheter implantation were performed. The influence on survival of demographics, uveal tumor characteristics, liver metastasis presentation, and treatment was studied. RESULTS: The median time to liver metastasis was 29 months. Twenty-eight patients (44%) were operated on: 14 (22%) had R0 liver surgery, and 14 with diffuse liver involvement had R2 liver surgery (there were no significant surgical complications). Thirty-five patients with diffuse liver involvement received systemic chemotherapy or best supportive care only. The median overall survival was 15 months (range, 3-110 months): 25 months for the 14 patients with R0 surgery, 16 months for the 14 with R2 surgery, and 11 months for the 35 with chemotherapy or supportive care. By univariate analysis, age (< or =70 years), number of metastases (< or =10), and quality of operation (R0) were predictive of a better prognosis. CONCLUSIONS: In the case of liver metastases from uveal melanoma, aggressive treatment permitting tumor eradication seems to offer a chance of long-term survival to selected patients. Nevertheless, neither ultrasound screening nor quality of operation had an effect on the outcome of most patients (78%). Better screening tests and more effective multimodality treatments are required to improve survival in uveal melanoma patients with hepatic metastases.

Négrier S. · No affiliation provided · Presse Med. · Pubmed #10923139 No free full text.

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Rivoire M, Kodjikian L, Négrier S. · No affiliation provided · Cancer. · Pubmed #15222009 links to  free full text

This publication has no abstract.