Jeffrey Sosman

..Future investigations of adjuvant vaccine approaches for patients with intermediate-thickness melanoma should involve larger numbers of patients and ideally should include sentinel node biopsy staging...

..Investigators in this field will need to carefully plan these trials so that at the end of the day, we learn from both the failures and successes of targeted therapy...

..Many of the above strategies are ongoing and will require careful phase 1 determination of toxicity and even more rigorous phase 2 analysis before moving onto phase 3 trials...

..The data suggest that inhibition downstream of BRAF should help to overcome acquired resistance...

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..The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial...

..Further studies are needed to determine whether combinations and/or sequencing of these targeted agents can further improve outcomes...

..We evaluated 210M with one of three different IL-2 schedules to determine whether a basis exists for a phase III trial...

..Once tolerability for combination regimens has been established, it will be critical to design informative phase 2 trials and address the benefit of combination versus sequential therapy...

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..This finding must now be confirmed in a large perspective observation-controlled clinical trial to solidify the role of Melacine as an effective cancer vaccine in melanoma...

..We postulated that the addition of O(6) benzylguanine (O(6)BG), a potent inactivator of AGT, would improve the clinical response to BCNU in melanoma...

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..The Cytokine Working Group conducted a randomized phase III trial to determine the value of outpatient interleukin-2 (IL-2) and interferon alfa-2b (IFN) relative to high-dose (HD) IL-2 in patients with metastatic renal cell carcinoma...

..This review updates the status of BRAF inhibitors in melanoma and what may be on the horizon...

..HLA-A2 and HLA-C3 contributed most to this effect. Processed melanoma peptides found in Melacine may be presented by HLA-A2 and HLA-C3 and play a role in preventing relapse in vaccinated patients...

..Tumor staging included torso computed tomography scans and brain magnetic resonance imaging pretreatment, after cycle 4 and then every 3 months for 2 years. Torso computed tomography scans were also performed after cycle 2...

..Our data indicate strongly that bortezomib in combination with chemotherapeutic agents should be studied additionally for the treatment of melanoma...

..This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma...

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..The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma...

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..We conducted a multicenter phase 2 trial to better define the clinical efficacy of thalidomide and temozolomide and the immune modulatory effects of thalidomide, when combined with temozolomide, in patients with metastatic melanoma...

..The levels of c-kit and/or PDGFR-alpha, -beta expression in the current study were lower than previously reported. Alternative treatment strategies remain a priority for patients with advanced melanoma...

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..DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile...

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..ABT-751 was investigated in this phase 1 trial designed to assess its maximum tolerated dose (MTD), dose-limiting toxicity (DLT), tolerability, and pharmacokinetics...

..This phase I study was designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of VEGF Trap administered intravenously (IV) every 2 weeks...

..This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC)...

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..A phase III trial indicated a survival benefit for Melacine in the subset of melanoma patients who express the HLA class I antigens A2 and/or HLA-C3. This finding must now be prospectively confirmed...

..To assess the safety and efficacy of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma (mRCC) and explore biomarkers for sunitinib response...

..Despite clinical efficacy, the study was closed prematurely owing to excess toxicity. Although all serious adverse events resolved, this degree of toxicity is unacceptable for an outpatient treatment regimen...

..The concordance between molecular cytogenetic techniques used to determine CNA has not been evaluated on a large set of loci in malignant melanoma...

..and Challenges in Melanoma, chaired by Michael Atkins and cochaired by Ulrich Keilholz, John Kirkwood, and Jeffrey Sosman, was held July 15 to 16, 2005, in Cambridge, Massachusetts...

..Simultaneous detection of more than three chromosomal or gene targets should increase the overall power of molecular cytogenetics by permitting detection of multiple genetic aberrations at the single cell level...

..The results indicate that the PSA 146-154 peptide emulates a naturally processed and presented peptide epitope of PSA that is within the T-cell repertoire of HLA-A2(+)patients with CaP...

..Thereby, the correlative studies described here may lead to the establishment of VEGF inhibition, VEGF Trap, specifically, as an approach to combine with and enhance cancer immunotherapy. ..

..By combining my efforts to merge laboratory efforts and immunologic endpoints with strong clinical trial design, I believe clinical research can better move tumor immunotherapy forward in a more rationale way. ..

..Thereby, the correlative studies described here may lead to the establishment of VEGF inhibition, VEGF Trap, specifically, as an approach to combine with and enhance cancer immunotherapy. ..

..Abstract Not Provided ..

..A better understanding of the basis for effective or even the mechanism underlying ineffective therapy will be critical to understanding how to proceed in the development of this drug and may influence the evaluation of other drugs. ..