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Melanoma News
ADJUVANT PEGYLATED INTERFERON IMPROVES DISEASE-FREE NOT OVERALL SURVIVAL
The results of the EORTC 18991 trial show that PEG-IFN (as compared to placebo) increases disease free but not overall survival in patients with stage III melanoma. At subgroup analysis, this survival advantage is maintained in patients with N1 disease (microscopic metastasis, as detected by sentinel node biopsy), but not in those with N2 disease (palpable lymph node metastasis).
Source: Eggermont AM et al, Lancet 2008, 372:117-26
NSAID & MELANOMA RISK/PROTECTION
A large cohort study (n = 63,809) showed no association between non-steroidal anti-inflammatory drugs (NSAID) use and melanoma risk (after adjusting for melanoma risk factors and indications for NSAID use). Moreover, NSAID use was not associated with tumor invasion, tumor thickness or risk of metastasis . NSAID do not appear to be good candidates for the chemoprevention of melanoma.
Source: Asgari MM et al, J Natl Cancer Inst 2008, Epub ahead of print
SENTINEL NODEL BIOPSY MAY IMPROVE SURVIVAL
Unlike the prospective randomized MSLT-I trial, a retrospective larger case-match-control study performed using data from the SEER database indicates that sentinel nodel biopsy improves the overall survival of patients with 0.75-3.5 mm thick melanoma.
Source: Gimotty P et al, J Clin Oncol 2008, 26 (May 20 suppl), Abstract 9005
TREMELIMUMAB (ANTI-CTLA4 ANTIBODY) IN ADVANCED MELANOMA
In a phase III RCT comparing the efficacy of first line anti-CTLA4 antibody Tremelimumab to physician's choice (Dacarbazine or Temozolomide) for the treatment of advanced/metastatic melanoma, investigators found no improvement in overall survival.
Source: Ribas A et al, J Clin Oncol 2008, 26 (May 20 suppl), Abstract LBA9011
ADJUVANT VACCINATION FOR STAGE II MELANOMA
In the largest adjuvant phase III RCT to date in stage II melanoma (EORTC 18961), investigators compared the efficacy and toxicity of ganglioside GM2-KLH21 vaccination to observation. The findings of this trial show that adjuvant GM2-KLH21 vaccination is ineffective and could even be detrimental in stage II melanoma patients.
Source: Eggermont AM et al, J Clin Oncol 2008, 26 (May 20 suppl), Abstract 9004
SUNBELT MELANOMA TRIAL: FINAL RESULTS
The final results of this multicenter prospective randomized trial failed to demonstrate a benefit for adjuvant high-dose interferon alpha (IFN) for patients with a single positive sentinel lymph node (SLN). Among patients with melanoma cells detected in the SLN by RT-PCR analysis, there was no significant benefit to completion lymph node dissection (CLND) or CLND + IFN.
Source: McMasters KM et al, J Clin Oncol 2008, 26 (May 20 suppl), Abstract 9003
NEWS FROM MOLECULAR EPIDEMIOLOGY STUDIES
Two recently published molecular epidemiology studies conducted on two large European series have shed further light on melanoma susceptibility genes. Besides confirming the relationship between melanocortin 1 receptor (MC1R) variants and risk of developing cutaneous melanoma, a highly significant association has been also found with polymorphisms at the tyrosinase (TYR), TYR related protein 1 (TYRP1) and aoguti signaling protein (ASIP) genes [1] and with sequence variants on chromosome 20q11.22 [2].
Source: [1] Gudbjartsson DF et al, Nat Genetics 2008, Epub ahead of print
[2] Brown KM et al, Nat Genetics 2008, Epub ahead of print
BIOCHEMOTHERAPY NOT RECOMMENDED BY CANADIAN GUIDELINES
The Melanoma Disease Site Group of Cancer Care Ontario's Program in Evidence-Based Care does not recommend the use of biochemotherapy (defined as a therapeutic regimen that includes chemotherapy [either single-agent or combination] and interleukin-2 [IL-2]) for the treatment of metastatic melanoma because of the inconsistent results of the available studies with regard to benefit (response, time to progression, and survival) and consistently high toxicity rates.
Source: Verma S et al, Curr Oncol 2008, 15:85-89
UNDER THE SPOTLIGHT: MELANOMA-PROMOTING MICRORNA
The promyelocytic leukemia zinc finger (PLZF) transcription factor has been found to act as a repressor of two microRNA (mir-221 and mir-222) by direct binding to their putative regulatory region. PLZF silencing in melanomas unblocks mir-221 and mir-222, which in turn controls the progression of the neoplasia through down-modulation of p27/Cip1/Kip1 and c-KIT receptor, leading to enhanced proliferation and differentiation blockade of the melanoma cells, respectively. In vitro and in vivo functional studies, including the use of antisense "antagomir" oligonucleotides, confirmed the key role of the two oncomirs in regulating the progression of human melanoma. These findings suggest that targeted therapies suppressing mir-221/mir-222 may be a novel anti-melanoma strategy.
Source: Felicetti F et al, Cancer Res 2008, 68:2745-54
IDENTIFICATION OF MELANOMA STEM CELLS OPENS NEW THERAPEUTIC ORIZONS
Investigators from the Children's Hospital (Harvard Medical School, Boston) have identified a subpopulation of melanoma cells that express the multidrug resistance (MDR) protein ABCB5 and that behave as stem cells (melanoma initiating cells) since they are capable of self-renewal and differentiation and are responsible for tumor growth. In human-to-mouse xenotransplantation experiments, ABCB5 positive melanoma cells possess greater tumorigenic capacity than ABCB5 negative bulk populations and re-establish clinical tumor heterogeneity. To test the hypothesis that melanoma stem cells are also required for growth of established tumors, a monoclonal antibody directed at ABCB5 (shown to induce antibody-dependent cell-mediated cytotoxicity) was systemically administered: the demonstration of a significant anticancer effect opens the avenue to the development of anti-melanoma stem cell therapy.
Source: Schatton T et al, Nature 2008, 451:345-9
ADJUVANT LOW DOSE INTERFERON (LDI): RESULTS OF A PHASE III RCT
The German Dermatologic Cooperative Oncology Group (DeCOG) has published the results of a phase III randomized controlled trial of LDI (3 MU s.c. of IFN alpha 2a three times a week for 2 years) versus LDI plus DTIC versus observation (n=444) for the adjuvant treatment of TNM stage III patients (after radical lymph node dissection). Investigators found that the 4-year overall survival rate of patients who had received LDI was 59%, while for those undergoing surgery alone was 42% (P = 0.0045). No improvement of survival was found for the combined treatment (LDI + DTIC).
Source: Garbe C et al, Ann Oncol 2008, Epub ahead of print
HEAT SHOCK PROTEIN (HSP) GP96 VACCINE: RESULTS OF A PHASE III RCT
In this international multicenter trial, TNM stage IV patients (n=322) were randomly assigned (2:1) to receive HSP vaccine (Vitespen) or physician's choice. Intention-to-treat analysis showed that overall survival in the vaccine arm is statistically indistinguishable from that in the control arm. Subgroup analysis showed that patients in TNM substages M1a and M1b who received a higher number of immunizations survived longer than those receiving fewer vaccine doses.
Source: Testori A et al, J Clin Oncol 2008, 26:955-62
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