Systematic Review of Medical Treatment in Melanoma: Current Status and Future Prospects
Tóm tắt
The incidence of melanoma is increasing worldwide, and the prognosis for patients with high-risk or advanced metastatic melanoma remains poor despite advances in the field. Standard treatment for patients with thick (≥2.0 mm) primary melanoma with or without regional metastases to lymph nodes is surgery followed by adjuvant therapy or clinical trial enrollment. Adjuvant therapy with interferon-α and cancer vaccines is discussed in detail. Patients who progress to stage IV metastatic melanoma have a median survival of ≤1 year. Standard treatment with chemotherapy yields low response rates, of which few are durable. Cytokine therapy with IL-2 achieves durable benefits in a greater fraction, but it is accompanied by severe toxicities that require the patient to be hospitalized for support during treatment. A systematic literature review of treatments for advanced, metastatic disease was conducted to present the success of current treatments and the promise of those still in clinical development that may yield incremental improvements in the treatment of advanced, metastatic melanoma.
Từ khóa
Tài liệu tham khảo
Lens, 2004, Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma, Br J Dermatol, 150, 179, 10.1111/j.1365-2133.2004.05708.x
Molife, 2002, Adjuvant therapy of malignant melanoma, Crit Rev Oncol Hematol, 44, 81, 10.1016/S1040-8428(02)00014-8
Wheatley, 2003, Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials, Cancer Treat Rev, 29, 241, 10.1016/S0305-7372(03)00074-4
Mocellin, 2010, Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis, J Natl Cancer Inst, 102, 493, 10.1093/jnci/djq009
Eggermont, 2004, Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?, Eur J Cancer, 40, 1825, 10.1016/j.ejca.2004.04.030
Atkins, 1999, High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993, J Clin Oncol, 17, 2105, 10.1200/JCO.1999.17.7.2105
Bajetta, 2006, Multicenter phase III randomized trial of polychemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-alpha2b in metastatic melanoma, Ann Oncol, 17, 571, 10.1093/annonc/mdl007
Ridolfi, 2002, Cisplatin, dacarbazine with or without subcutaneous interleukin-2, and interferon alpha-2b in advanced melanoma outpatients: results from an Italian multicenter phase III randomized clinical trial, J Clin Oncol, 20, 1600, 10.1200/JCO.2002.20.6.1600
Atkins, 2008, Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group, J Clin Oncol, 26, 5748, 10.1200/JCO.2008.17.5448
Lewis, 2006, Phase II multicenter study of neoadjuvant biochemotherapy for patients with stage III malignant melanoma, J Clin Oncol, 24, 3157, 10.1200/JCO.2005.04.5344
Eigentler, 2003, Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials, Lancet Oncol, 4, 748, 10.1016/S1470-2045(03)01280-4
Balch, 2009, Final version of 2009 AJCC melanoma staging and classification, J Clin Oncol, 27, 6199, 10.1200/JCO.2009.23.4799
Garbe, 2010, Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline, Eur J Cancer, 46, 270, 10.1016/j.ejca.2009.10.032
Thomas, 2004, Excision margins in high-risk malignant melanoma, N Engl J Med, 350, 757, 10.1056/NEJMoa030681
Balch, 2000, Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial, Ann Surg Oncol, 7, 87, 10.1007/s10434-000-0087-9
Fecher, 2009, Where are we with adjuvant therapy of stage III and IV melanoma in 2009?, J Natl Compr Canc Netw, 7, 295, 10.6004/jnccn.2009.0022
Kirkwood, 1996, Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684, J Clin Oncol, 14, 7, 10.1200/JCO.1996.14.1.7
Creagan, 1995, Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma, J Clin Oncol, 13, 2776, 10.1200/JCO.1995.13.11.2776
Kirkwood, 2000, High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190, J Clin Oncol, 18, 2444, 10.1200/JCO.2000.18.12.2444
Eggermont, 2005, Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial, Lancet, 366, 1189, 10.1016/S0140-6736(05)67482-X
Hancock, 2004, Adjuvant interferon in high-risk melanoma: the AIM HIGH Study–United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma, J Clin Oncol, 22, 53, 10.1200/JCO.2004.03.185
Pehamberger, 1998, Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group, J Clin Oncol, 16, 1425, 10.1200/JCO.1998.16.4.1425
Cascinelli, 2001, Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial, Lancet, 358, 866, 10.1016/S0140-6736(01)06068-8
Garbe, 2008, Adjuvant low-dose interferon α2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis, Ann Oncol, 19, 1195, 10.1093/annonc/mdn001
Grob, 1998, Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma, Lancet, 351, 1905, 10.1016/S0140-6736(97)12445-X
Eggermont, 2007, Randomized adjuvant therapy trials in melanoma: surgical and systemic, Semin Oncol, 34, 509, 10.1053/j.seminoncol.2007.09.003
Cameron, 2001, Adjuvant interferon alpha 2b in high risk melanoma—the Scottish study, Br J Cancer, 84, 1146, 10.1054/bjoc.2000.1623
Lens, 2002, Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials, J Clin Oncol, 20, 1818, 10.1200/JCO.2002.07.070
Garbe, 2007, Diagnosis and treatment of cutaneous melanoma: state of the art 2006, Melanoma Res, 17, 117, 10.1097/CMR.0b013e328042bb36
Wheatley, 2007, Interferon-{alpha} as adjuvant therapy for melanoma: an individual patient data meta-analysis of randomised trials, J Clin Oncol, 25
Eggermont, 2008, Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial, Lancet, 372, 117, 10.1016/S0140-6736(08)61033-8
Chiarion-Sileni, 2006, Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Intergroup trial, BMC Cancer, 6, 44, 10.1186/1471-2407-6-44
U.S. National Institutes of Health, Pegylated Interferon-Alpha-2a in Patients With Malignant Melanoma Stage IIA–IIIB
U.S. National Institutes of Health, PegIntron Versus IntronA in CMAJCC Stage II (EADO 2001/CMII Trial)
Grob, 2010, Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macro-metastatic nodes: EADO trial, J Clin Oncol, 28
Pectasides, 2009, Randomized phase III study of 1 month versus 1 year of adjuvant high-dose interferon alfa-2b in patients with resected high-risk melanoma, J Clin Oncol, 27, 939, 10.1200/JCO.2008.16.3121
Hauschild, 2009, Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma, J Clin Oncol, 27, 3496, 10.1200/JCO.2008.21.3892
Moschos, 2006, Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses, J Clin Oncol, 24, 3164, 10.1200/JCO.2005.05.2498
Yurkovetsky, 2007, Multiplex analysis of serum cytokines in melanoma patients treated with interferon-alpha2b, Clin Cancer Res, 13, 2422, 10.1158/1078-0432.CCR-06-1805
Zarour, 2003, Melanoma vaccines: early progress and future promises, Semin Cutan Med Surg, 22, 68, 10.1053/sder.2003.50006
Kirkwood, 2001, High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801, J Clin Oncol, 19, 2370, 10.1200/JCO.2001.19.9.2370
Isreal, 2001, Naturally occuring and GMK-induced antibodies to GM2 in high-risk melanoma patients in study E1694/S9512/CALGB 509801, J Clin Oncol, 20
Morton, 2007, An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites, J Clin Oncol, 25
Eggermont, 2010, Randomized phase III trial comparing postoperative adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation in stage II (T3–T4N0M0) melanoma: final results of study EORTC 18961, J Clin Oncol, 28
U.S. National Institutes of Health, A Phase III Study to Test the Benefit of a New Kind of Anti-cancer Treatment in Patients With Melanoma, After Surgical Removal of Their Tumor
Kirkwood, 2009, Immunogenicity and antitumor effects of vaccination with peptide vaccine+/-granulocyte-monocyte colony-stimulating factor and/or IFN-alpha2b in advanced metastatic melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696, Clin Cancer Res, 15, 1443, 10.1158/1078-0432.CCR-08-1231
Gogas, 2006, Prognostic significance of autoimmunity during treatment of melanoma with interferon, N Engl J Med, 354, 709, 10.1056/NEJMoa053007
U.S. National Institutes of Health, Efficacy Study of Ipilimumab Versus Placebo to Prevent Recurrence After Complete Resection of High Risk Stage III Melanoma
Avril, 2004, Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study, J Clin Oncol, 22, 1118, 10.1200/JCO.2004.04.165
Middleton, 2007, Results of a multicenter randomized study to evaluate the safety and efficacy of combined immunotherapy with interleukin-2, interferon-{alpha}2b and histamine dihydrochloride versus dacarbazine in patients with stage IV melanoma, Ann Oncol, 18, 1691, 10.1093/annonc/mdm331
Bedikian, 2006, Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group, J Clin Oncol, 24, 4738, 10.1200/JCO.2006.06.0483
Schadendorf, 2006, Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG, Ann Oncol, 17, 563, 10.1093/annonc/mdj138
Ranson, 2007, Randomized trial of the combination of lomeguatrib and temozolomide compared with temozolomide alone in chemotherapy naive patients with metastatic cutaneous melanoma, J Clin Oncol, 25, 2540, 10.1200/JCO.2007.10.8217
Kaufmann, 2005, Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group, J Clin Oncol, 23, 9001, 10.1200/JCO.2005.01.1551
Bafaloukos, 2005, Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma: a randomized phase II study of the Hellenic Cooperative Oncology Group, Ann Oncol, 16, 950, 10.1093/annonc/mdi190
Danson, 2003, Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma, J Clin Oncol, 21, 2551, 10.1200/JCO.2003.10.039
McDermott, 2008, Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group, J Clin Oncol, 26, 2178, 10.1200/JCO.2007.14.8288
Atzpodien, 2002, Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM), Br J Cancer, 86, 179, 10.1038/sj.bjc.6600043
Keilholz, 2005, Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group, J Clin Oncol, 23, 6747, 10.1200/JCO.2005.03.202
Punt, 2006, Chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha2b and interleukin-2 versus two cycles of dacarbazine followed by chemoimmunotherapy in patients with metastatic melanoma: a randomised phase II study of the European Organization for Research and Treatment of Cancer Melanoma Group, Eur J Cancer, 42, 2991, 10.1016/j.ejca.2006.08.012
Richtig, 2004, Temozolomide and interferon alpha 2b in metastatic melanoma stage IV, Br J Dermatol, 151, 91, 10.1111/j.1365-2133.2004.06019.x
Glover, 2003, Phase II randomized trial of cisplatin and WR-2721 versus cisplatin alone for metastatic melanoma: an Eastern Cooperative Oncology Group Study (E1686), Melanoma Res, 13, 619, 10.1097/00008390-200312000-00012
Vuoristo, 2005, Randomized trial of dacarbazine versus bleomycin, vincristine, lomustine and dacarbazine (BOLD) chemotherapy combined with natural or recombinant interferon-alpha in patients with advanced melanoma, Melanoma Res, 15, 291, 10.1097/00008390-200508000-00010
Reichle, 2007, Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial, Melanoma Res, 17, 360, 10.1097/CMR.0b013e3282f1d2c8
Hauschild, 2009, Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma, J Clin Oncol, 27, 2823, 10.1200/JCO.2007.15.7636
Maio, 2010, Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma, J Clin Oncol, 28, 1780, 10.1200/JCO.2009.25.5208
Lens, 2003, Systemic chemotherapy in the treatment of malignant melanoma, Expert Opin Pharmacother, 4, 2205, 10.1517/14656566.4.12.2205
Patel, 2008, Extended schedule, escalated dose Temozolomide versus Dacarbazine in Stage IV malignant melanoma: Final results of the randomised phase III study (EORTC 18032), Ann Oncol, 19
Parkinson, 1990, Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study, J Clin Oncol, 8, 1650, 10.1200/JCO.1990.8.10.1650
Agarwala, 2003, Improving survival in patients with high-risk and metastatic melanoma: immunotherapy leads the way, Am J Clin Dermatol, 4, 333, 10.2165/00128071-200304050-00004
Atkins, 2006, Cytokine-based therapy and biochemotherapy for advanced melanoma, Clin Cancer Res, 12, 2353s, 10.1158/1078-0432.CCR-05-2503
Keilholz, 1997, Recombinant interleukin-2-based treatments for advanced melanoma: the experience of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group, Cancer J Sci Am, 3, S22
Balmer, 1991, Clinical use of biologic response modifiers in cancer treatment: an overview. Part II. Colony-stimulating factors and interleukin-2, DICP, 25, 490, 10.1177/106002809102500509
Bruton, 1994, Recombinant interleukin-2, Pharmacotherapy, 14, 635, 10.1002/j.1875-9114.1994.tb04156.x
Schwartzentruber, 2009, A phase III multi-institutional randomized study of immunization with the gp100: 209–217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma, J Clin Oncol, 27
U.S. National Institutes of Health, M-Vax + Low Dose Interleukin-2 Versus Placebo Vaccine in Metastatic Melanoma in Patients With Stage IV Melanoma
U.S. National Institutes of Health, Chemotherapy With or Without Immunotherapy in Treating Patients With Stage III or Stage IV Melanoma
Hauschild, 2001, Dacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG), Br J Cancer, 84, 1036, 10.1054/bjoc.2001.1731
Ives, 2007, Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients, J Clin Oncol, 25, 5426, 10.1200/JCO.2007.12.0253
O'Day, 2009, Phase II multicenter trial of maintenance biotherapy after induction concurrent Biochemotherapy for patients with metastatic melanoma, J Clin Oncol, 27, 6207, 10.1200/JCO.2008.20.3075
U.S. National Institutes of Health, Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma
U.S. National Institutes of Health, Elesclomol (STA-4783) With Paclitaxel Versus Paclitaxel Alone in Melanoma
U.S. National Institutes of Health, Trial of Dacarbazine With or Without Genasense in Advanced Melanoma
Hodi, 2010, Improved Survival with Ipilimumab in Patients with Metastatic Melanoma, N Engl J Med, 363, 711, 10.1056/NEJMoa1003466
U.S. National Institutes of Health, Carboplatin and Paclitaxel With or Without Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Melanoma
U.S. National Institutes of Health, A Study of RO5185426 in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma
U.S. National Institutes of Health, A Study of Tasisulam Versus Paclitaxel as Treatment for Metastatic Melanoma
U.S. National Institutes of Health, A Trial of ABI-007 Versus Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma
Ribas, 2008, Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide [TMZ] or dacarbazine [DTIC]) in patients with advanced melanoma, J Clin Oncol, 26
Ribas, 2005, Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206, J Clin Oncol, 23, 8968, 10.1200/JCO.2005.01.109
Ribas, 2007, Tremelimumab (CP-675,206), a cytotoxic T lymphocyte associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancer, The Oncologist, 12, 873, 10.1634/theoncologist.12-7-873
Attia, 2005, Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4, J Clin Oncol, 23, 6043, 10.1200/JCO.2005.06.205
Maker, 2005, Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study, Ann Surg Oncol, 12, 1005, 10.1245/ASO.2005.03.536
Gomez-Navarro, 2007, Survival of patients (pts) with metastatic melanoma treated with the anti-CTLA4 monoclonal antibody (mAb) CP-675,206 in a phase I/II study, J Clin Oncol, 25
Weber, 2007, The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma, J Clin Oncol, 25
Kirkwood, 2008, A phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma, J Clin Oncol, 26
O'Day, 2008, Efficacy and safety of ipilimumab induction and maintenance dosing in patients with advanced melanoma who progressed on one or more prior therapies, J Clin Oncol, 26
Hamid, 2007, Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma, J Clin Oncol, 25
Flaherty, 2006, Chemotherapy and targeted therapy combinations in advanced melanoma, Clin Cancer Res, 12, 2366s, 10.1158/1078-0432.CCR-05-2505
Satyamoorthy, 2003, Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation, Cancer Res, 63, 756
Amaravadi, 2007, Updated results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma, J Clin Oncol, 25
Flaherty, 2010, Final results of E2603: a double-blind, randomized phase III trial comparing carboplatin (C)/paclitaxel (P) with or without sorafenib (S) in metastatic melanoma, J Clin Oncol, 28
Eisen, 2006, Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis, Br J Cancer, 95, 581, 10.1038/sj.bjc.6603291
Flaherty, 2009, Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer, J Clin Oncol, 27
McArthur, 2010, Early FDG-PET responses to PLX4032 in BRAF-mutant advanced melanoma, J Clin Oncol, 28
U.S. National Institutes of Health, A Phase I Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2118436 in Subjects With Solid Tumors
U.S. National Institutes of Health, A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma
Kefford, 2010, Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors, J Clin Oncol, 28
Davies, 2007, AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models, Mol Cancer Ther, 6, 2209, 10.1158/1535-7163.MCT-07-0231
Dummer, 2008, AZD6244 (ARRY-142886) vs temozolomide (TMZ) in patients (pts) with advanced melanoma: an open-label, randomized, multicenter, phase II study, J Clin Oncol, 26
U.S. National Institutes of Health, Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients
Infante, 2010, Safety and efficacy results from the first-in-human study of the oral MEK 1/2 inhibitor GSK1120212, J Clin Oncol, 28
Kirkwood, 2010, A phase II study of tasisulam sodium (LY573636) as second-line treatment for patients with unresectable or metastatic melanoma, J Clin Oncol, 28
Dudley, 2003, Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients, J Immunother, 26, 332, 10.1097/00002371-200307000-00005
Dudley, 2008, Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens, J Clin Oncol, 26, 5233, 10.1200/JCO.2008.16.5449
Dudley, 2005, Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma, J Clin Oncol, 23, 2346, 10.1200/JCO.2005.00.240
Besser, 2009, Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients, J Immunother, 32, 415, 10.1097/CJI.0b013e31819c8bda
Koike, 2008, Nonmyeloablative chemotherapy followed by T-cell adoptive transfer and dendritic cell-based vaccination results in rejection of established melanoma, J Immunother, 31, 402, 10.1097/CJI.0b013e31816cabbb
Wallen, 2009, Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma, PLoS One, 4, e4749, 10.1371/journal.pone.0004749
Hauschild, 2009, Phase III, randomized, double-blind study of elesclomol and paclitaxel versus paclitaxel alone in stage IV metastatic melanoma (MM), J Clin Oncol, 27
Bedikian, 2010, Results of pooled analyses from two phase III trials of 1,085 patients (pts) with advanced melanoma: oblimersen (OBL) plus dacarbazine (DTIC) versus DTIC alone, J Clin Oncol, 28
Cancer Research, U.K. A trial looking at bevacizumab after surgery for melanoma skin cancer (AVAST-M)
U.S. National Institutes of Health, Efficacy and Safety Study of OncoVEXGM-CSF Compared to GM-CSF in Melanoma