Page last updated: 2024-10-19

niacinamide and Melanoma

niacinamide has been researched along with Melanoma in 122 studies

nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.

Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)

Research Excerpts

ExcerptRelevanceReference
"The aim of the study was to analyse efficacy, safety, and health-related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma."9.22Sorafenib in metastatic uveal melanoma: efficacy, toxicity and health-related quality of life in a multicentre phase II study. ( Delcambre, C; Dutriaux, C; Heutte, N; Joly, F; Lesimple, T; Mouriaux, F; Neidhart-Berard, EM; Parienti, JJ; Penel, N; Peyro Saint Paul, L; Pham, AD; Piperno-Neumann, S; Servois, V; Thyss, A, 2016)
"We observed improved treatment response with CPS in patients with melanoma whose tumors have RAF1 (cRAF), KRAS, or CCND1 amplification, all of which can be attributed to sorafenib targeting CRAF."9.22Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma. ( D'Andrea, K; Flaherty, KT; Khare, S; Kirkwood, JM; Kluger, HM; Lee, SJ; Nathanson, KL; Rimm, DL; Roszik, J; Schuchter, LM; Wilson, MA; Woodman, SE; Wubbenhorst, B; Zhao, F, 2016)
"Patients with metastatic melanoma were enrolled in dose-escalation cohorts to determine the maximum tolerated dose (MTD) of sorafenib (twice daily) in combination with bortezomib (weekly for 3 of 4 weeks)."9.20A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma. ( Aldridge, J; Atkins, MB; Conley, C; Flaherty, KT; Giobbie-Hurder, A; Hodi, FS; Ibrahim, N; Lawrence, DP; McDermott, DF; Mier, JW; Sullivan, RJ, 2015)
" We assessed the association of somatic mutations with clinicopathologic features and clinical outcomes in patients with metastatic melanoma treated on E2603, comparing treatment with carboplatin, paclitaxel ± sorafenib (CP vs."9.19Correlation of somatic mutations and clinical outcome in melanoma patients treated with Carboplatin, Paclitaxel, and sorafenib. ( D'Andrea, K; Flaherty, KT; Kirkwood, JM; Kluger, HM; Lee, SJ; Letrero, R; Nathanson, KL; Rimm, DL; Schuchter, LM; Wilson, MA; Zhao, F, 2014)
"This study was designed to evaluate the safety and feasibility of high-dose interleukin-2 (HD IL-2) followed by sorafenib in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC)."9.19A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma. ( Bhinder, A; Carson, WE; Clinton, SK; Geyer, S; Kendra, K; Lam, E; Lesinski, GB; Mace, TA; Monk, P; Mortazavi, A; Olencki, T; Tahiri, S, 2014)
"In a multicenter phase-II-DeCOG study (NCT00623402) in 10 dermato-oncology centers, 55 patients with metastatic melanoma received a combination of sorafenib (2 x 400 mg/day orally) and pegylated interferon alpha-2b (3 μg/kg body weight 1 x/week subcutaneously)."9.17Cutaneous side effects of combined therapy with sorafenib and pegylated interferon alpha-2b in metastatic melanoma (phase II DeCOG trial). ( Degen, A; Egberts, F; Garbe, C; Gutzmer, R; Hauschild, A; Kilian, K; Poppe, LM; Trefzer, U; Ugurel, S; Weichenthal, M, 2013)
"The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma."9.17Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. ( Atkins, MB; Flaherty, KT; Flaherty, L; Kefford, R; Kirkwood, JM; Lee, SJ; Leming, P; Schuchter, LM; Zhao, F, 2013)
"Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors."9.16Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512. ( Aparicio, AM; Bhatia, S; Lao, CD; Margolin, KA; Moon, J; Othus, M; Ribas, A; Sondak, VK; Weber, JS, 2012)
"Heavily pretreated patients with stage IV melanoma were started on sorafenib 400 mg twice daily (bid)."9.16Sorafenib in advanced melanoma: a critical role for pharmacokinetics? ( Avril, MF; Billemont, B; Blanchet, B; Coriat, R; Franck, N; Goldwasser, F; Lebbe, C; Mir, O; Pécuchet, N; Tod, M; Viguier, M, 2012)
"Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate."9.16A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity. ( Augustine, C; Beasley, GM; Brady, MS; Coleman, AP; Davies, MA; Peterson, BL; Raymond, A; Sanders, G; Selim, MA; Tyler, DS, 2012)
"This phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma."9.16Phase I study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma. ( Bassett, RL; Bedikian, AY; Culotta, KS; Dancey, JE; Davies, MA; Deng, W; Fox, PS; Gupta, S; Huang, S; Hwu, P; Hwu, WJ; Kim, KB; Lazar, AJ; Liu, W; Madden, TL; Ng, CS; Papadopoulos, NE; Prieto, VG; Wright, JJ; Xu, Q, 2012)
"Patients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 μg/kg once per week, and sorafenib 400-mg b."9.15Sorafenib and pegylated interferon-α2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial. ( Becker, JC; Berking, C; Degen, A; Egberts, F; Frey, L; Garbe, C; Gutzmer, R; Hassel, JC; Hauschild, A; Kaehler, KC; Livingstone, E; Mauch, C; Mohr, P; Rass, K; Schadendorf, D; Schenck, F; Trefzer, U; Ugurel, S; Weichenthal, M; Wilhelm, T, 2011)
" This phase I/II study in patients with advanced melanoma evaluated the potential effect of sorafenib on the pharmacokinetics of midazolam, omeprazole, and dextromethorphan, specific substrates of CYP3A4, CYP2C19, and CYP2D6, respectively."9.15Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. ( Flaherty, KT; Frye, RF; Lathia, C; O'Dwyer, PJ; Redlinger, M; Rosen, M; Schuchter, L, 2011)
"The safety of oral sorafenib up to a maximum protocol-specified dose combined with dacarbazine in patients with metastatic, histologically confirmed melanoma was investigated in a phase I dose-escalation study and the activity of the combination was explored in an open-label phase II study."9.15Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. ( Affolter, A; Ahmad, T; Chao, D; Chevreau, C; Corrie, P; Eisen, T; Gibbens, I; Gore, ME; Harries, M; James, MG; Jouary, T; Lorigan, P; Marais, R; Montegriffo, E; Nathan, PD; Negrier, S; Ottensmeier, C; Prendergast, S; Robert, C; Strauss, UP, 2011)
"Sorafenib monotherapy in patients with metastatic melanoma was explored in this multi-institutional phase II study."9.14A phase II trial of sorafenib in metastatic melanoma with tissue correlates. ( Buckley, M; Christos, PJ; Goldberg, L; Hamilton, A; Liebes, L; Min, C; Osman, I; Ott, PA; Pavlick, AC; Polsky, D; Safarzadeh-Amiri, S; Wright, JJ; Yee, H; Yoon, J, 2010)
" Sorafenib, carboplatin, and paclitaxel (SCP) has antitumor activity in melanoma patients, but no association was found between response and activating B-Raf V600E mutations."9.14Expression of sorafenib targets in melanoma patients treated with carboplatin, paclitaxel and sorafenib. ( Camp, RL; Flaherty, KT; Jilaveanu, L; Kluger, HM; Lee, SJ; Nathanson, KL; Rimm, DL; Zito, C, 2009)
"This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma."9.13Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group. ( Agarwala, S; Beeram, M; Cranmer, L; Frenette, G; Gonzalez, R; Hersh, E; Hodi, FS; Jakub, JW; Kirkwood, J; Lewis, K; Linette, GP; McDermott, DF; Patel, K; Puzanov, I; Richards, J; Sosman, JA; Tarantolo, S; White, JM; Xia, C, 2008)
"The effects of sorafenib--an oral multikinase inhibitor targeting the tumour and tumour vasculature--were evaluated in patients with advanced melanoma enrolled in a large multidisease Phase II randomised discontinuation trial (RDT)."9.12Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. ( Ahmad, T; Eisen, T; Flaherty, KT; Gibbens, I; Gore, M; Hackett, S; James, M; Kaye, S; Marais, R; Nathanson, KL; O'Dwyer, PJ; Poulin-Costello, M; Ratain, MJ; Schuchter, LM; Schwartz, B; Simantov, R; Xia, C, 2006)
"To determine the safety, maximum tolerated dose, pharmacokinetics, and efficacy, and to evaluate biomarkers, of the multikinase inhibitor sorafenib plus IFN alpha-2a in advanced renal cell carcinoma (RCC) or melanoma."9.12Phase I trial of sorafenib in combination with IFN alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma. ( Angevin, E; Armand, JP; Brendel, E; Chami, L; Escudier, B; Lamuraglia, M; Landreau, V; Lassau, N; Robert, C; Schwartz, B; Soria, JC; Zafarana, E, 2007)
" Additionally, clinical trial databases were examined to identify and summarize ongoing trials of sorafenib in melanoma patients."8.88Sorafenib in melanoma. ( Dummer, R; Karpova, MB; Levesque, MP; Mangana, J, 2012)
" Vemurafenib and sorafenib treatment did not significantly reduce the total CSE1L levels; however, they inhibited ERK1/2 and CSE1L phosphorylation in A375 melanoma cells and HT-29 colorectal cancer cells."7.81Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts. ( Chen, YC; Chin, SY; Chou, CL; Jiang, MC; Lee, WR; Liu, KH; Shen, SC; Shih, YH; Tseng, JT, 2015)
" We previously showed that the multikinase inhibitor sorafenib activated GSK-3β and that this activation attenuated the cytotoxic effects of the drug in various BRAF-mutant melanoma cell lines."7.77Differential modulatory effects of GSK-3β and HDM2 on sorafenib-induced AIF nuclear translocation (programmed necrosis) in melanoma. ( Liu, Q; Mier, JW; Panka, DJ, 2011)
"A 66-year-old man with malignant melanoma was treated with sorafenib, 2 yen 400 mg per day."7.75Multiple colon ulcerations, perforation and death during treatment of malignant melanoma with sorafenib. ( Frieling, T; Heise, J; Wassilew, SW, 2009)
"Dasatinib has both anti-proliferative and anti-invasive effects in melanoma cells and combined with chemotherapy may have clinical benefit in the treatment of malignant melanoma."7.74Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines. ( Clynes, M; Crown, J; Eustace, AJ; O'Donovan, N, 2008)
" We previously demonstrated that the multikinase inhibitor sorafenib induces apoptosis in melanoma cell lines."7.74GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines. ( Atkins, MB; Cho, DC; Mier, JW; Panka, DJ, 2008)
"Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents."6.79Regulation of CD4(+)NKG2D(+) Th1 cells in patients with metastatic melanoma treated with sorafenib: role of IL-15Rα and NKG2D triggering. ( Aupérin, A; Ayyoub, M; Caignard, A; Caillat-Zucman, S; Chaba, K; Chaput, N; Dessen, P; Eggermont, A; Flament, C; Jacquelot, N; Jacques, Y; Mateus, C; Messaoudene, M; Mortier, E; Poirier-Colame, V; Porta, C; Robert, C; Romero, AI; Rusakiewicz, S; Valmori, D; Vielh, P; Zitvogel, L, 2014)
"Sorafenib was given orally at 200 mg BiD for 5 days every week; bevacizumab was administered 5 mg/kg intravenously every 14 days."6.79Phase II study evaluating the efficacy, safety, and pharmacodynamic correlative study of dual antiangiogenic inhibition using bevacizumab in combination with sorafenib in patients with advanced malignant melanoma. ( Beeram, M; Benjamin, D; Ketchum, N; Mahalingam, D; Malik, L; Michalek, J; Mita, A; Rodon, J; Sankhala, K; Sarantopoulos, J; Tolcher, A; Wright, J, 2014)
"Sorafenib is an oral multikinase inhibitor that targets 2 classes of kinases which are known to be involved in both tumor proliferation and angiogenesis."6.44Metastatic melanoma: scientific rationale for sorafenib treatment and clinical results. ( Egberts, F; Hauschild, A; Kahler, KC; Livingstone, E, 2008)
"α-Mangostin is a natural product commonly used in Asia for cosmetic and medicinal applications including topical treatment of acne and skin cancer."5.43Inhibition of Cell Proliferation in an NRAS Mutant Melanoma Cell Line by Combining Sorafenib and α-Mangostin. ( Chen, H; Fisher, DE; Li, Y; Sun, J; Westover, KD; Xia, Y; Zhang, J, 2016)
"Melanoma is the most aggressive and deadly form of cutaneous neoplasm due to its propensity to metastasize."5.43Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma. ( Afaq, F; Athar, M; Diamond, AC; Elmets, CA; Kappes, JC; Katiyar, SK; Pal, HC; Strickland, LR, 2016)
"Melanoma is the most deadly form of cutaneous malignancy, and its incidence rates are rising worldwide."5.42Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. ( Afaq, F; Agarwal, J; Athar, M; Baxter, RD; Elmets, CA; Hunt, KM; Pal, HC, 2015)
"Most metastatic melanomas are refractory to current available therapy, underscoring the need to identify new effective treatments."5.37Fluvastatin enhances sorafenib cytotoxicity in melanoma cells via modulation of AKT and JNK signaling pathways. ( Doudican, NA; Orlow, SJ; Quay, E; Zhang, S, 2011)
"Melanoma is the most lethal human skin cancer."5.36The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. ( Gil, R; Grueso, J; Hernandez-Losa, J; López-Fauqued, M; Moliné, T; Pujol, A; Recio, JA, 2010)
"The aim of the study was to analyse efficacy, safety, and health-related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma."5.22Sorafenib in metastatic uveal melanoma: efficacy, toxicity and health-related quality of life in a multicentre phase II study. ( Delcambre, C; Dutriaux, C; Heutte, N; Joly, F; Lesimple, T; Mouriaux, F; Neidhart-Berard, EM; Parienti, JJ; Penel, N; Peyro Saint Paul, L; Pham, AD; Piperno-Neumann, S; Servois, V; Thyss, A, 2016)
"We observed improved treatment response with CPS in patients with melanoma whose tumors have RAF1 (cRAF), KRAS, or CCND1 amplification, all of which can be attributed to sorafenib targeting CRAF."5.22Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma. ( D'Andrea, K; Flaherty, KT; Khare, S; Kirkwood, JM; Kluger, HM; Lee, SJ; Nathanson, KL; Rimm, DL; Roszik, J; Schuchter, LM; Wilson, MA; Woodman, SE; Wubbenhorst, B; Zhao, F, 2016)
"Patients with metastatic melanoma were enrolled in dose-escalation cohorts to determine the maximum tolerated dose (MTD) of sorafenib (twice daily) in combination with bortezomib (weekly for 3 of 4 weeks)."5.20A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma. ( Aldridge, J; Atkins, MB; Conley, C; Flaherty, KT; Giobbie-Hurder, A; Hodi, FS; Ibrahim, N; Lawrence, DP; McDermott, DF; Mier, JW; Sullivan, RJ, 2015)
" We assessed the association of somatic mutations with clinicopathologic features and clinical outcomes in patients with metastatic melanoma treated on E2603, comparing treatment with carboplatin, paclitaxel ± sorafenib (CP vs."5.19Correlation of somatic mutations and clinical outcome in melanoma patients treated with Carboplatin, Paclitaxel, and sorafenib. ( D'Andrea, K; Flaherty, KT; Kirkwood, JM; Kluger, HM; Lee, SJ; Letrero, R; Nathanson, KL; Rimm, DL; Schuchter, LM; Wilson, MA; Zhao, F, 2014)
"This study was designed to evaluate the safety and feasibility of high-dose interleukin-2 (HD IL-2) followed by sorafenib in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC)."5.19A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma. ( Bhinder, A; Carson, WE; Clinton, SK; Geyer, S; Kendra, K; Lam, E; Lesinski, GB; Mace, TA; Monk, P; Mortazavi, A; Olencki, T; Tahiri, S, 2014)
"In a multicenter phase-II-DeCOG study (NCT00623402) in 10 dermato-oncology centers, 55 patients with metastatic melanoma received a combination of sorafenib (2 x 400 mg/day orally) and pegylated interferon alpha-2b (3 μg/kg body weight 1 x/week subcutaneously)."5.17Cutaneous side effects of combined therapy with sorafenib and pegylated interferon alpha-2b in metastatic melanoma (phase II DeCOG trial). ( Degen, A; Egberts, F; Garbe, C; Gutzmer, R; Hauschild, A; Kilian, K; Poppe, LM; Trefzer, U; Ugurel, S; Weichenthal, M, 2013)
"The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma."5.17Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. ( Atkins, MB; Flaherty, KT; Flaherty, L; Kefford, R; Kirkwood, JM; Lee, SJ; Leming, P; Schuchter, LM; Zhao, F, 2013)
"Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate."5.16A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity. ( Augustine, C; Beasley, GM; Brady, MS; Coleman, AP; Davies, MA; Peterson, BL; Raymond, A; Sanders, G; Selim, MA; Tyler, DS, 2012)
"Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors."5.16Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512. ( Aparicio, AM; Bhatia, S; Lao, CD; Margolin, KA; Moon, J; Othus, M; Ribas, A; Sondak, VK; Weber, JS, 2012)
"Heavily pretreated patients with stage IV melanoma were started on sorafenib 400 mg twice daily (bid)."5.16Sorafenib in advanced melanoma: a critical role for pharmacokinetics? ( Avril, MF; Billemont, B; Blanchet, B; Coriat, R; Franck, N; Goldwasser, F; Lebbe, C; Mir, O; Pécuchet, N; Tod, M; Viguier, M, 2012)
"This phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma."5.16Phase I study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma. ( Bassett, RL; Bedikian, AY; Culotta, KS; Dancey, JE; Davies, MA; Deng, W; Fox, PS; Gupta, S; Huang, S; Hwu, P; Hwu, WJ; Kim, KB; Lazar, AJ; Liu, W; Madden, TL; Ng, CS; Papadopoulos, NE; Prieto, VG; Wright, JJ; Xu, Q, 2012)
" This phase I/II study in patients with advanced melanoma evaluated the potential effect of sorafenib on the pharmacokinetics of midazolam, omeprazole, and dextromethorphan, specific substrates of CYP3A4, CYP2C19, and CYP2D6, respectively."5.15Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. ( Flaherty, KT; Frye, RF; Lathia, C; O'Dwyer, PJ; Redlinger, M; Rosen, M; Schuchter, L, 2011)
"Patients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 μg/kg once per week, and sorafenib 400-mg b."5.15Sorafenib and pegylated interferon-α2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial. ( Becker, JC; Berking, C; Degen, A; Egberts, F; Frey, L; Garbe, C; Gutzmer, R; Hassel, JC; Hauschild, A; Kaehler, KC; Livingstone, E; Mauch, C; Mohr, P; Rass, K; Schadendorf, D; Schenck, F; Trefzer, U; Ugurel, S; Weichenthal, M; Wilhelm, T, 2011)
"The safety of oral sorafenib up to a maximum protocol-specified dose combined with dacarbazine in patients with metastatic, histologically confirmed melanoma was investigated in a phase I dose-escalation study and the activity of the combination was explored in an open-label phase II study."5.15Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. ( Affolter, A; Ahmad, T; Chao, D; Chevreau, C; Corrie, P; Eisen, T; Gibbens, I; Gore, ME; Harries, M; James, MG; Jouary, T; Lorigan, P; Marais, R; Montegriffo, E; Nathan, PD; Negrier, S; Ottensmeier, C; Prendergast, S; Robert, C; Strauss, UP, 2011)
" Sorafenib, carboplatin, and paclitaxel (SCP) has antitumor activity in melanoma patients, but no association was found between response and activating B-Raf V600E mutations."5.14Expression of sorafenib targets in melanoma patients treated with carboplatin, paclitaxel and sorafenib. ( Camp, RL; Flaherty, KT; Jilaveanu, L; Kluger, HM; Lee, SJ; Nathanson, KL; Rimm, DL; Zito, C, 2009)
"Sorafenib monotherapy in patients with metastatic melanoma was explored in this multi-institutional phase II study."5.14A phase II trial of sorafenib in metastatic melanoma with tissue correlates. ( Buckley, M; Christos, PJ; Goldberg, L; Hamilton, A; Liebes, L; Min, C; Osman, I; Ott, PA; Pavlick, AC; Polsky, D; Safarzadeh-Amiri, S; Wright, JJ; Yee, H; Yoon, J, 2010)
"This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma."5.13Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group. ( Agarwala, S; Beeram, M; Cranmer, L; Frenette, G; Gonzalez, R; Hersh, E; Hodi, FS; Jakub, JW; Kirkwood, J; Lewis, K; Linette, GP; McDermott, DF; Patel, K; Puzanov, I; Richards, J; Sosman, JA; Tarantolo, S; White, JM; Xia, C, 2008)
"The effects of sorafenib--an oral multikinase inhibitor targeting the tumour and tumour vasculature--were evaluated in patients with advanced melanoma enrolled in a large multidisease Phase II randomised discontinuation trial (RDT)."5.12Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. ( Ahmad, T; Eisen, T; Flaherty, KT; Gibbens, I; Gore, M; Hackett, S; James, M; Kaye, S; Marais, R; Nathanson, KL; O'Dwyer, PJ; Poulin-Costello, M; Ratain, MJ; Schuchter, LM; Schwartz, B; Simantov, R; Xia, C, 2006)
"To determine the safety, maximum tolerated dose, pharmacokinetics, and efficacy, and to evaluate biomarkers, of the multikinase inhibitor sorafenib plus IFN alpha-2a in advanced renal cell carcinoma (RCC) or melanoma."5.12Phase I trial of sorafenib in combination with IFN alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma. ( Angevin, E; Armand, JP; Brendel, E; Chami, L; Escudier, B; Lamuraglia, M; Landreau, V; Lassau, N; Robert, C; Schwartz, B; Soria, JC; Zafarana, E, 2007)
" Additionally, clinical trial databases were examined to identify and summarize ongoing trials of sorafenib in melanoma patients."4.88Sorafenib in melanoma. ( Dummer, R; Karpova, MB; Levesque, MP; Mangana, J, 2012)
" Vemurafenib and sorafenib treatment did not significantly reduce the total CSE1L levels; however, they inhibited ERK1/2 and CSE1L phosphorylation in A375 melanoma cells and HT-29 colorectal cancer cells."3.81Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts. ( Chen, YC; Chin, SY; Chou, CL; Jiang, MC; Lee, WR; Liu, KH; Shen, SC; Shih, YH; Tseng, JT, 2015)
"Bortezomib, clusianone 502 (nemorosone), ranpirnase, and sorafenib were efficient in inhibiting the growth of conjunctival melanoma cell lines."3.79Chemosensitivity of conjunctival melanoma cell lines to target-specific chemotherapeutic agents. ( Bornfeld, N; Freistuehler, M; Hilger, RA; Scheulen, M; Steuhl, KP; Westekemper, H, 2013)
"Autophagy was measured in tumor biopsies obtained from metastatic melanoma patients enrolled on a phase II trial of temozolomide and sorafenib and correlated to clinical outcome."3.77Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma. ( Amaravadi, RK; Li, LZ; Lum, JJ; Ma, XH; McAfee, QW; Nathanson, KL; Piao, S; Wang, D, 2011)
"Melanoma cell lines that express GRM1 and either wild-type B-RAF or mutated B-RAF were treated with riluzole, sorafenib, PLX4720, or the combination of riluzole either with sorafenib or with PLX4720."3.77Glutamatergic pathway targeting in melanoma: single-agent and combinatorial therapies. ( Chan, JL; Chen, S; Goydos, JS; Lee, HJ; Namkoong, J; Rosenberg, S; Shin, SS; Wall, BA; Wangari-Talbot, J, 2011)
" Because treatment with the kinase inhibitor sorafenib decreased NHE1 activity in HeLa and HEK cells, we examined the role of B-Raf in regulating NHE1 in malignant melanoma cells."3.77B-Raf associates with and activates the NHE1 isoform of the Na+/H+ exchanger. ( Fliegel, L; Karki, P; Li, X; Schrama, D, 2011)
" We previously showed that the multikinase inhibitor sorafenib activated GSK-3β and that this activation attenuated the cytotoxic effects of the drug in various BRAF-mutant melanoma cell lines."3.77Differential modulatory effects of GSK-3β and HDM2 on sorafenib-induced AIF nuclear translocation (programmed necrosis) in melanoma. ( Liu, Q; Mier, JW; Panka, DJ, 2011)
"A 66-year-old man with malignant melanoma was treated with sorafenib, 2 yen 400 mg per day."3.75Multiple colon ulcerations, perforation and death during treatment of malignant melanoma with sorafenib. ( Frieling, T; Heise, J; Wassilew, SW, 2009)
"Dasatinib has both anti-proliferative and anti-invasive effects in melanoma cells and combined with chemotherapy may have clinical benefit in the treatment of malignant melanoma."3.74Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines. ( Clynes, M; Crown, J; Eustace, AJ; O'Donovan, N, 2008)
"Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture."3.74Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment. ( Busch, S; Garbe, C; Herlyn, M; Kulms, D; Lasithiotakis, K; Maczey, E; Meier, F; Schittek, B, 2007)
"Migration of HUVEC cells, the ability of HUVEC cells to form tubes, and proliferative capacity of a human ocular melanoma cell line were tested in the presence of lenalidomide and sorafenib alone and in combination."3.74Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma. ( Blansfield, JA; Kachala, S; Libutti, SK; Lorang, D; Mangiameli, DP; Muller, GW; Schafer, PH; Stirling, DI, 2007)
" We previously demonstrated that the multikinase inhibitor sorafenib induces apoptosis in melanoma cell lines."3.74GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines. ( Atkins, MB; Cho, DC; Mier, JW; Panka, DJ, 2008)
"Two human melanoma cell lines, MM96 and MM127, were found to be highly sensitive to the toxicity of adenosine (D50 100-150 micrograms/ml) compared with other melanoma lines."3.66Differential effects of NAD, nicotinamide and related compounds upon growth and nucleoside incorporation in human cells. ( Hayward, IP; Parsons, PG, 1983)
"Twenty non-melanoma skin cancer patients with positive HIF-1α and p53 expressions were selected and randomly divided into two groups, the placebo group and the experimental group."2.90Correlation of changes in HIF-1α and p53 expressions with vitamin B3 deficiency in skin cancer patients. ( Liu, T; Mou, Y; Yang, H; Zhang, H, 2019)
"To analyse ophthalmological adverse events associated with mitogen-activated protein kinase kinase (MEK) inhibition with pimasertib treatment for metastatic cutaneous melanoma (CM)."2.87Pimasertib-associated ophthalmological adverse events. ( Boon, CJF; Jager, MJ; Kruit, WHJ; Luyten, GPM; van Dijk, EHC; Vingerling, JR, 2018)
"Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents."2.79Regulation of CD4(+)NKG2D(+) Th1 cells in patients with metastatic melanoma treated with sorafenib: role of IL-15Rα and NKG2D triggering. ( Aupérin, A; Ayyoub, M; Caignard, A; Caillat-Zucman, S; Chaba, K; Chaput, N; Dessen, P; Eggermont, A; Flament, C; Jacquelot, N; Jacques, Y; Mateus, C; Messaoudene, M; Mortier, E; Poirier-Colame, V; Porta, C; Robert, C; Romero, AI; Rusakiewicz, S; Valmori, D; Vielh, P; Zitvogel, L, 2014)
"Sorafenib was given orally at 200 mg BiD for 5 days every week; bevacizumab was administered 5 mg/kg intravenously every 14 days."2.79Phase II study evaluating the efficacy, safety, and pharmacodynamic correlative study of dual antiangiogenic inhibition using bevacizumab in combination with sorafenib in patients with advanced malignant melanoma. ( Beeram, M; Benjamin, D; Ketchum, N; Mahalingam, D; Malik, L; Michalek, J; Mita, A; Rodon, J; Sankhala, K; Sarantopoulos, J; Tolcher, A; Wright, J, 2014)
" Clinical and pharmacodynamic activity was observed in kidney cancer and melanoma."2.75Safety, efficacy, pharmacokinetics, and pharmacodynamics of the combination of sorafenib and tanespimycin. ( Burger, AM; Egorin, MJ; Heilbrun, LK; Horiba, MN; Ivy, P; Li, J; Lorusso, PM; Pacey, S; Sausville, EA; Vaishampayan, UN, 2010)
" Ocular toxicity was assessed and handled according to the Common Terminology Criteria for Adverse Events."2.52Ocular Toxicity in Metastatic Melanoma Patients Treated With Mitogen-Activated Protein Kinase Kinase Inhibitors: A Case Series. ( Alessio, G; Guida, M; Niro, A; Recchimurzo, N; Sborgia, L; Strippoli, S, 2015)
"Sorafenib is an oral multikinase inhibitor that targets 2 classes of kinases which are known to be involved in both tumor proliferation and angiogenesis."2.44Metastatic melanoma: scientific rationale for sorafenib treatment and clinical results. ( Egberts, F; Hauschild, A; Kahler, KC; Livingstone, E, 2008)
"Approved for the treatment of advanced renal cell carcinoma by the US FDA and other regulatory agencies, sorafenib is an agent with multiple targets that may also prove beneficial in other malignancies."2.44Sorafenib: delivering a targeted drug to the right targets. ( Flaherty, KT, 2007)
"Sorafenib is a small molecule inhibitor of several kinases involved in tumour proliferation and tumour angiogenesis including Raf, VEGFR and platelet derived growth factor receptor."2.43Sorafenib. ( Rini, BI, 2006)
"Cutaneous immune-related adverse events (irAEs) occur in more than one-third of patients treated with immune checkpoint inhibitors; they are often the first clinical manifestation, although they may occur months after initiation of therapy."1.72Cutaneous immune-related adverse events and photodamaged skin in patients with metastatic melanoma: could nicotinamide be useful? ( Colombo, J; Covarelli, P; De Giorgi, V; Doni, L; Silvestri, F; Stanganelli, I; Trane, L; Venturi, F; Zuccaro, B, 2022)
"α-Mangostin is a natural product commonly used in Asia for cosmetic and medicinal applications including topical treatment of acne and skin cancer."1.43Inhibition of Cell Proliferation in an NRAS Mutant Melanoma Cell Line by Combining Sorafenib and α-Mangostin. ( Chen, H; Fisher, DE; Li, Y; Sun, J; Westover, KD; Xia, Y; Zhang, J, 2016)
" In BRAF-mutant melanomas, orally bioavailable B-Raf inhibitors, such as vemurafenib, achieve dramatic responses initially, but this is followed by rapid emergence of resistance driven by numerous mechanisms and requiring second-generation treatment approaches."1.43B-Raf Inhibition in the Clinic: Present and Future. ( Fiskus, W; Mitsiades, N, 2016)
"Anal melanoma is a rare malignancy with a poor prognosis."1.43A case series of anal melanoma including the results of treatment with imatinib in selected patients. ( Henderson, M; Heriot, AG; Knowles, J; Lynch, AC; Warrier, SK, 2016)
"Melanoma is the most aggressive and deadly form of cutaneous neoplasm due to its propensity to metastasize."1.43Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma. ( Afaq, F; Athar, M; Diamond, AC; Elmets, CA; Kappes, JC; Katiyar, SK; Pal, HC; Strickland, LR, 2016)
"Melanoma is the most deadly form of cutaneous malignancy, and its incidence rates are rising worldwide."1.42Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. ( Afaq, F; Agarwal, J; Athar, M; Baxter, RD; Elmets, CA; Hunt, KM; Pal, HC, 2015)
"Early diagnosis of malignant melanoma is important for patient survival."1.42Synthesis and evaluation of ¹²³/¹³¹I-Iochlonicotinamide as a novel SPECT probe for malignant melanoma. ( Chang, CC; Chang, CH; Chen, CL; Lin, MH; Liu, RS; Shen, CC; Wang, HE, 2015)
"Metastatic melanoma is associated with a splicing switch to pro-angiogenic VEGF-A, previously shown to be regulated by SRSF1 phosphorylation by SRPK1."1.40Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma. ( Bates, DO; Coupland, SE; Dean, R; Gammons, MV; Lucas, R; Oltean, S, 2014)
"Cutaneous melanoma is a significant cause of morbidity and mortality."1.40Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes. ( Damian, DL; Halliday, GM; Surjana, D; Thompson, BC, 2014)
"Melanoma is highly metastatic, but the mechanism of melanoma cell migration is still unclear."1.40SIRT1 regulates lamellipodium extension and migration of melanoma cells. ( Hayashi, T; Hirobe, T; Hisahara, S; Horimoto, K; Horio, Y; Jimbow, K; Kunimoto, R; Sato, M; Sugino, T; Tanimura, A; Yamashita, T, 2014)
"Cotreatment with sorafenib and diclofenac interrupts a positive feedback signaling loop involving extracellular signal-regulated kinase, cellular phospholipase A2, and COX."1.38Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma. ( Axelrod, M; Capaldo, BJ; Gioeli, D; Jensen, K; Mackey, A; Roller, DG; Weber, MJ, 2012)
"Most metastatic melanomas are refractory to current available therapy, underscoring the need to identify new effective treatments."1.37Fluvastatin enhances sorafenib cytotoxicity in melanoma cells via modulation of AKT and JNK signaling pathways. ( Doudican, NA; Orlow, SJ; Quay, E; Zhang, S, 2011)
"Cutaneous melanoma is a tumor with rising incidence and a very poor prognosis at the disseminated stage."1.37Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition. ( Bedeir, A; Berger, W; Ghassemi, S; Grasl-Kraupp, B; Grusch, M; Heffeter, P; Heinzle, C; Held, G; Holzmann, K; Marian, B; Metzner, T; Micksche, M; Peter-Vörösmarty, B; Pirker, C; Spiegl-Kreinecker, S, 2011)
"Melanoma is the most lethal human skin cancer."1.36The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. ( Gil, R; Grueso, J; Hernandez-Losa, J; López-Fauqued, M; Moliné, T; Pujol, A; Recio, JA, 2010)
"As sorafenib has poor cellular activity against the BRAF V600E mutation, the conclusion that many researchers have arrived at is that sorafenib did not provide a test of the therapeutic value of BRAF inhibition."1.35Development of a novel chemical class of BRAF inhibitors offers new hope for melanoma treatment. ( Flaherty, KT; Smalley, KS, 2009)
"The combined treatment of melanoma cells with sorafenib and rapamycin led to an approximately twofold increase of cell death compared with sorafenib monotreatment (P<0."1.35Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells. ( Flaherty, KT; Garbe, C; Kulms, D; Lasithiotakis, KG; Maczey, E; Meier, FE; Schittek, B; Sinnberg, TW, 2008)

Research

Studies (122)

TimeframeStudies, this research(%)All Research%
pre-19902 (1.64)18.7374
1990's1 (0.82)18.2507
2000's36 (29.51)29.6817
2010's78 (63.93)24.3611
2020's5 (4.10)2.80

Authors

AuthorsStudies
De Giorgi, V1
Colombo, J1
Trane, L1
Silvestri, F1
Venturi, F1
Zuccaro, B1
Doni, L1
Stanganelli, I1
Covarelli, P1
Moreira, GA1
Caetano, MMM1
do Vale, JA1
de Paiva, JC1
Gonçalves, VHS1
Almeida, AA1
Silva, LVG1
Martim, FRG1
de Andrade Barros, MV1
Guimarães, GR1
de Oliveira Santos, L1
de Souza, APM1
Machado-Neves, M1
Teixeira, RR1
Silva-Júnior, A1
Fietto, JLR1
Boroni, M1
de Oliveira, LL1
Bressan, GC1
Zhang, H2
Liu, X1
Chen, Y1
Xu, R1
He, S1
Malesu, R1
Martin, AJ1
Lyons, JG1
Scolyer, RA1
Chen, AC1
McKenzie, CA1
Madore, J1
Halliday, GM3
Damian, DL4
Lebbé, C2
Italiano, A1
Houédé, N1
Awada, A1
Aftimos, P1
Lesimple, T2
Dinulescu, M1
Schellens, JHM1
Leijen, S1
Rottey, S1
Kruse, V1
Kefford, R2
Raymond, E1
Faivre, S1
Pages, C1
Gomez-Roca, C1
Schueler, A1
Goodstal, S1
Massimini, G1
Delord, JP1
Lim, SY1
Menzies, AM1
Rizos, H1
Minocha, R1
Liu, T1
Yang, H1
Mou, Y1
van Dijk, EHC1
Kruit, WHJ1
Jager, MJ1
Luyten, GPM1
Vingerling, JR1
Boon, CJF1
Buonvicino, D1
Mazzola, F1
Zamporlini, F1
Resta, F1
Ranieri, G1
Camaioni, E1
Muzzi, M1
Zecchi, R1
Pieraccini, G1
Dölle, C1
Calamante, M1
Bartolucci, G1
Ziegler, M1
Stecca, B1
Raffaelli, N1
Chiarugi, A1
Itzhaki, O1
Greenberg, E1
Shalmon, B1
Kubi, A1
Treves, AJ1
Shapira-Frommer, R1
Avivi, C1
Ortenberg, R1
Ben-Ami, E1
Schachter, J1
Besser, MJ1
Markel, G1
Pavlick, AC2
Bahadoran, P3
Allegra, M3
Le Duff, F1
Long-Mira, E1
Hofman, P1
Giacchero, D2
Passeron, T2
Lacour, JP2
Ballotti, R3
Degen, A3
Weichenthal, M2
Ugurel, S2
Trefzer, U2
Kilian, K1
Garbe, C5
Egberts, F3
Poppe, LM1
Hauschild, A5
Gutzmer, R3
Botton, T1
Yeh, I1
Nelson, T1
Vemula, SS1
Sparatta, A1
Garrido, MC1
Rocchi, S1
McCalmont, TH1
LeBoit, PE1
Burton, EA1
Bollag, G2
Bastian, BC1
Romero, AI1
Chaput, N1
Poirier-Colame, V1
Rusakiewicz, S1
Jacquelot, N1
Chaba, K1
Mortier, E1
Jacques, Y1
Caillat-Zucman, S1
Flament, C1
Caignard, A1
Messaoudene, M1
Aupérin, A1
Vielh, P1
Dessen, P1
Porta, C1
Mateus, C1
Ayyoub, M1
Valmori, D1
Eggermont, A1
Robert, C3
Zitvogel, L1
Li, B1
Wang, G1
Yang, M1
Xu, Z1
Zeng, B1
Wang, H1
Shen, J1
Chen, K1
Zhu, W1
Kunimoto, R1
Jimbow, K1
Tanimura, A1
Sato, M1
Horimoto, K1
Hayashi, T1
Hisahara, S1
Sugino, T1
Hirobe, T1
Yamashita, T1
Horio, Y1
Monk, P1
Lam, E1
Mortazavi, A1
Kendra, K1
Lesinski, GB1
Mace, TA1
Geyer, S1
Carson, WE1
Tahiri, S1
Bhinder, A1
Clinton, SK1
Olencki, T1
Holderfield, M1
Nagel, TE1
Stuart, DD1
Wilson, MA2
Zhao, F3
Letrero, R2
D'Andrea, K2
Rimm, DL4
Kirkwood, JM4
Kluger, HM4
Lee, SJ4
Schuchter, LM5
Flaherty, KT11
Nathanson, KL6
Niederkorn, A1
Wackernagel, W1
Artl, M1
Schwantzer, G1
Aigner, B1
Richtig, E1
Thompson, BC1
Surjana, D1
Mahalingam, D1
Malik, L1
Beeram, M2
Rodon, J1
Sankhala, K1
Mita, A1
Benjamin, D1
Ketchum, N1
Michalek, J1
Tolcher, A1
Wright, J1
Sarantopoulos, J1
Gammons, MV1
Lucas, R1
Dean, R1
Coupland, SE1
Oltean, S1
Bates, DO1
Leguerney, I1
Scoazec, JY1
Gadot, N1
Robin, N1
Pénault-Llorca, F1
Victorin, S1
Lassau, N2
Chang, CC1
Chang, CH1
Shen, CC1
Chen, CL1
Liu, RS1
Lin, MH1
Wang, HE1
Leight, JL1
Tokuda, EY1
Jones, CE1
Lin, AJ1
Anseth, KS1
Sullivan, RJ1
Ibrahim, N1
Lawrence, DP1
Aldridge, J1
Giobbie-Hurder, A1
Hodi, FS2
Conley, C1
Mier, JW4
Atkins, MB4
McDermott, DF2
Lee, WR1
Shen, SC1
Shih, YH1
Chou, CL1
Tseng, JT1
Chin, SY1
Liu, KH1
Chen, YC1
Jiang, MC1
Niro, A1
Strippoli, S1
Alessio, G1
Sborgia, L1
Recchimurzo, N1
Guida, M1
Pal, HC2
Baxter, RD1
Hunt, KM1
Agarwal, J1
Elmets, CA2
Athar, M2
Afaq, F2
Khare, S1
Roszik, J1
Woodman, SE2
Wubbenhorst, B1
Diamond, AC1
Strickland, LR1
Kappes, JC1
Katiyar, SK1
Knowles, J1
Lynch, AC1
Warrier, SK1
Henderson, M1
Heriot, AG1
Fiskus, W1
Mitsiades, N1
Okano, S1
Xia, Y1
Li, Y1
Westover, KD1
Sun, J1
Chen, H1
Zhang, J1
Fisher, DE1
Mouriaux, F1
Servois, V1
Parienti, JJ1
Thyss, A2
Dutriaux, C1
Neidhart-Berard, EM1
Penel, N1
Delcambre, C1
Peyro Saint Paul, L1
Pham, AD1
Heutte, N1
Piperno-Neumann, S1
Joly, F1
Tran, MA1
Smith, CD2
Kester, M1
Robertson, GP2
Kahler, KC1
Livingstone, E2
Fecher, LA1
Amaravadi, R1
Alexandrescu, DT1
McClure, R1
Farzanmehr, H1
Dasanu, CA1
Melnikova, VO1
Bar-Eli, M1
Lopez, V1
Pinazo, I1
Marti, N1
Monteagudo, C1
Jorda, E1
Smalley, KS2
Xiao, M1
Villanueva, J1
Nguyen, TK1
Van Belle, P1
Elder, DE1
Wang, Y1
Herlyn, M3
Eustace, AJ1
Crown, J1
Clynes, M1
O'Donovan, N1
Quintás-Cardama, A1
Lazar, AJ2
Kim, K1
Ross, M1
Hwu, P2
Poust, J1
Jilaveanu, L1
Zito, C1
Camp, RL2
Yang, J1
Zaja-Milatovic, S1
Thu, YM1
Lee, F1
Smykla, R1
Richmond, A1
Dhomen, N1
Marais, R4
Frieling, T1
Heise, J1
Wassilew, SW1
Greguric, I3
Taylor, SR2
Denoyer, D3
Ballantyne, P1
Berghofer, P1
Roselt, P3
Pham, TQ1
Mattner, F1
Bourdier, T1
Neels, OC3
Dorow, DS3
Loc'h, C1
Hicks, RJ3
Katsifis, A3
Subbiah, V1
Wolff, JE1
Jilaveanu, LB1
Zito, CR1
Aziz, SA1
Conrad, PJ1
Schmitz, JC1
Sznol, M1
López-Fauqued, M1
Gil, R1
Grueso, J1
Hernandez-Losa, J1
Pujol, A1
Moliné, T1
Recio, JA1
Kim, HJ1
Jung, MH2
Kim, H3
El-Gamal, MI4
Sim, TB1
Lee, SH1
Hong, JH2
Hah, JM3
Cho, JH1
Choi, JH1
Yoo, KH5
Oh, CH5
Karreth, FA1
DeNicola, GM1
Winter, SP1
Tuveson, DA2
Lee, J1
Yu, H3
Chung, JY1
Sim, T3
Aide, N1
Bertsch, A1
Jung, S1
Zerck, A1
Pfeifer, N1
Nahnsen, S1
Henneges, C1
Nordheim, A1
Kohlbacher, O1
Wellbrock, C1
Hurlstone, A1
Handolias, D1
Hamilton, AL1
Salemi, R1
Tan, A1
Moodie, K1
Kerr, L1
Dobrovic, A1
McArthur, GA1
Vaishampayan, UN1
Burger, AM1
Sausville, EA1
Heilbrun, LK1
Li, J1
Horiba, MN1
Egorin, MJ1
Ivy, P1
Pacey, S1
Lorusso, PM1
Augustine, CK1
Toshimitsu, H1
Jung, SH1
Zipfel, PA1
Yoo, JS1
Yoshimoto, Y1
Selim, MA3
Burchette, J1
Beasley, GM2
McMahon, N1
Padussis, J1
Pruitt, SK1
Ali-Osman, F1
Tyler, DS3
Satzger, I1
Voelker, B1
Kapp, A1
Wallach, I1
Jaitly, N1
Lilien, R1
Niessner, H1
Beck, D1
Sinnberg, T1
Lasithiotakis, K2
Maczey, E3
Gogel, J1
Venturelli, S1
Berger, A1
Mauthe, M1
Toulany, M1
Flaherty, K1
Schaller, M1
Schadendorf, D2
Proikas-Cezanne, T1
Schittek, B3
Kulms, D3
Meier, F2
Solit, D1
Rosen, N1
Potdevin, T1
Kirby, L1
Raymond, AK1
Puri, PK1
Nelson, KC1
Ott, PA1
Hamilton, A1
Min, C1
Safarzadeh-Amiri, S1
Goldberg, L1
Yoon, J1
Yee, H1
Buckley, M1
Christos, PJ1
Wright, JJ2
Polsky, D1
Osman, I1
Liebes, L1
Becker, JC1
Schenck, F1
Frey, L1
Wilhelm, T1
Hassel, JC1
Mauch, C1
Berking, C1
Rass, K1
Mohr, P1
Kaehler, KC1
Ma, XH1
Piao, S1
Wang, D1
McAfee, QW1
Lum, JJ1
Li, LZ1
Amaravadi, RK1
Karki, P1
Li, X1
Schrama, D1
Fliegel, L1
Lathia, C1
Frye, RF1
Schuchter, L1
Redlinger, M1
Rosen, M1
O'Dwyer, PJ2
Kim, MH1
Kim, M1
Heo, J1
Breitbach, CJ1
Moon, A1
Kim, CW1
Patt, R1
Kim, MK1
Lee, YK1
Oh, SY1
Woo, HY1
Parato, K1
Rintoul, J1
Falls, T1
Hickman, T1
Rhee, BG1
Bell, JC1
Kirn, DH1
Hwang, TH1
Lee, WS1
Bourcier, C1
Griseri, P1
Grépin, R1
Bertolotto, C2
Mazure, N1
Pagès, G1
Boulinguez, S1
Eisen, T2
Affolter, A1
Lorigan, P1
Corrie, P1
Ottensmeier, C1
Chevreau, C1
Chao, D1
Nathan, PD1
Jouary, T1
Harries, M1
Negrier, S1
Montegriffo, E1
Ahmad, T2
Gibbens, I2
James, MG1
Strauss, UP1
Prendergast, S1
Gore, ME1
Metzner, T1
Bedeir, A1
Held, G1
Peter-Vörösmarty, B1
Ghassemi, S1
Heinzle, C1
Spiegl-Kreinecker, S1
Marian, B1
Holzmann, K1
Grasl-Kraupp, B1
Pirker, C1
Micksche, M1
Berger, W1
Heffeter, P1
Grusch, M1
Lee, HJ1
Wall, BA1
Wangari-Talbot, J1
Shin, SS1
Rosenberg, S1
Chan, JL1
Namkoong, J1
Goydos, JS1
Chen, S1
Liu, Q1
Panka, DJ3
Choi, HS1
Cho, HG1
Zhang, S1
Doudican, NA1
Quay, E1
Orlow, SJ1
Park, JH1
Lee, YS1
Ségalen, C1
Deville, A1
Ortonne, JP1
Davies, MA2
Fox, PS1
Papadopoulos, NE1
Bedikian, AY1
Hwu, WJ1
Prieto, VG1
Culotta, KS1
Madden, TL1
Xu, Q1
Huang, S1
Deng, W1
Ng, CS1
Gupta, S1
Liu, W1
Dancey, JE1
Bassett, RL1
Kim, KB1
Margolin, KA2
Moon, J2
Flaherty, LE1
Lao, CD2
Akerley, WL1
Othus, M2
Sosman, JA2
Sondak, VK2
Mangana, J1
Levesque, MP1
Karpova, MB1
Dummer, R1
Coleman, AP1
Raymond, A1
Sanders, G1
Peterson, BL1
Brady, MS1
Augustine, C1
Pécuchet, N1
Mir, O1
Billemont, B1
Blanchet, B1
Franck, N1
Viguier, M1
Coriat, R1
Tod, M1
Avril, MF1
Goldwasser, F1
Westekemper, H1
Freistuehler, M1
Bornfeld, N1
Steuhl, KP1
Scheulen, M1
Hilger, RA1
Roller, DG1
Axelrod, M1
Capaldo, BJ1
Jensen, K1
Mackey, A1
Weber, MJ1
Gioeli, D1
Bhatia, S1
Weber, JS1
Aparicio, AM1
Ribas, A1
Flaherty, L1
Leming, P1
WOODS, M1
BURK, D1
Karasarides, M1
Chiloeches, A1
Hayward, R1
Niculescu-Duvaz, D1
Scanlon, I1
Friedlos, F1
Ogilvie, L1
Hedley, D1
Martin, J1
Marshall, CJ1
Springer, CJ1
Sharma, A1
Trivedi, NR1
Zimmerman, MA1
Wang, W1
Rini, BI1
Gore, M1
Kaye, S1
Hackett, S1
James, M1
Xia, C2
Simantov, R1
Schwartz, B2
Poulin-Costello, M1
Ratain, MJ1
Gollob, JA1
Wilhelm, S1
Carter, C2
Kelley, SL1
Murphy, DA1
Makonnen, S1
Lassoued, W1
Feldman, MD1
Lee, WM1
Escudier, B1
Angevin, E1
Soria, JC1
Chami, L1
Lamuraglia, M1
Zafarana, E1
Landreau, V1
Brendel, E1
Armand, JP1
Busch, S1
Kumar, SM1
Edwards, R1
Chen, L1
Kazianis, S1
Brafford, P1
Acs, G1
Xu, X1
Mangiameli, DP1
Blansfield, JA1
Kachala, S1
Lorang, D1
Schafer, PH1
Muller, GW1
Stirling, DI1
Libutti, SK1
Cho, DC1
Lasithiotakis, KG1
Sinnberg, TW1
Meier, FE1
Moncrieff, M1
Shannon, K1
Hong, A1
Hersey, P1
Thompson, J1
Gonzalez, R1
Linette, GP1
Richards, J1
Jakub, JW1
Tarantolo, S1
Agarwala, S1
Frenette, G1
Puzanov, I1
Cranmer, L1
Lewis, K1
Kirkwood, J1
White, JM1
Patel, K1
Hersh, E1
Parsons, PG1
Hayward, IP1
Thomas, CD1
Stern, S1
Chaplin, DJ1
Guichard, M1

Clinical Trials (13)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours[NCT00982865]Phase 1182 participants (Actual)Interventional2007-12-31Completed
Detection of Plasmatic Cell-free BRAF and NRAS Mutations: a New Tool for Monitoring Patients With Metastatic Malignant Melanoma Treated With Targeted Therapies or Immunotherapy ( MALT )[NCT03493230]35 participants (Anticipated)Interventional2018-04-30Not yet recruiting
A Phase I Study of Bolus High Dose Interleukin-2 With Sorafenib (BAY 43-9006) in Patients With Unresectable or Metastatic Clear Cell Renal Carcinoma (RCC) and Metastatic Melanoma[NCT00418496]Phase 117 participants (Actual)Interventional2006-11-08Completed
A Phase II, Pharmacokinetic (PK), Pharmacodynamic (PD) and Biological Correlative Study of the Efficacy and Safety of Dual Antiangiogenic Inhibition Using Bevacizumab and Sorafenib in Patients With Advanced Malignant Melanoma[NCT00387751]Phase 214 participants (Actual)Interventional2006-08-31Completed
A Phase I Expanded Cohort Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma[NCT01078961]Phase 111 participants (Actual)Interventional2010-09-30Completed
A Phase II Study of BAY 43-9006 (NSC 724772) in Unresectable Stage III and IV Melanoma (IND 69,869)[NCT00119249]Phase 274 participants (Anticipated)Interventional2005-06-30Completed
A Phase II, Multi-center, Open-label, Uncontrolled Study to Evaluate the Efficacy and Safety of BAY 43-9006 Given Daily in Combination With Repeated 21-Day Cycles of Dacarbazine (DTIC) Chemotherapy in Subjects With Advanced Metastatic Melanoma.[NCT00492297]Phase 283 participants (Actual)Interventional2005-04-30Completed
Sorafenib Administered Using a High-dose, Pulsatile Regimen in Patients With Advanced Solid Malignancies: a Phase I Exposure Escalation Study[NCT02636426]Phase 117 participants (Actual)Interventional2015-09-30Completed
Phase II Trial of BAY 43-9006 (Sorafenib; NSC-724772) in Combination With Carboplatin and Paclitaxel in Patients With Metastatic Uveal Melanoma[NCT00329641]Phase 225 participants (Actual)Interventional2011-02-28Completed
A Double-Blind, Randomized, Placebo-Controlled Phase III Trial of Carboplatin, Paclitaxel and Sorafenib Versus Carboplatin, Paclitaxel and Placebo in Patients With Unresectable Locally Advanced or Stage IV Melanoma[NCT00110019]Phase 3823 participants (Actual)Interventional2005-06-30Completed
Randomized Phase II Trial Assessing the Combination of Nexavar® (Sorafenib), and Gemcitabine/Oxaliplatin in Patients Treated for Advanced (Unresectable/Metastatic) Hepatocellular Carcinoma.[NCT00941967]Phase 278 participants (Actual)Interventional2008-12-31Completed
Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated CLL With Four or Six Cycles of Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide Followed by Lenalidomide Consolidation/ Maintenance[NCT01723839]Phase 221 participants (Actual)Interventional2012-02-22Completed
Phase II Randomized, Placebo Controlled Study of Sorafenib in Repeated Cycles of 21 Days in Combination With Dacarbazine (DTIC) Chemotherapy in Subjects With Unresectable Stage III or Stage IV Melanoma[NCT00110994]Phase 2101 participants (Actual)Interventional2005-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21

DLT was defined as any of following toxicities at any dose level according to using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) v3.0(CTCAE), probably or possibly related to trial medication by investigator or sponsor: a)Any Grade 3 or more non-haematological toxicity excluding: (i)Grade 3 asymptomatic increase in liver function tests (Aspartate Aminotransferase, Alanine transaminase, Alkaline Phosphatase reversible within 7 days for subjects without liver involvement, or grade 4 for subjects with liver involvement; (ii)Grade 3 vomiting if it is encountered despite adequate and optimal therapy (e.g. serotonin [5HT3] antagonists and corticosteroids); (iii)Grade 3 diarrhoea if it is encountered despite adequate and optimal anti diarrhoea therapy; b)Grade 4 neutropenia of >5 days duration or febrile neutropenia lasting for more than 1 day; c)Grade 4 thrombocytopenia >1 day or grade 3 with bleeding; d)Any treatment delay >2 weeks due to drug-related AEs. (NCT00982865)
Timeframe: Day 1 up to Day 21 of Cycle 1

InterventionSubjects (Number)
MSC1936369B Regimen 12
MSC1936369B Regimen 2 (Without Food Effect + With Food Effect)6
MSC1936369B Regimen 3 Once Daily (QD)0
MSC1936369B Regimen 3 Twice Daily6

Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death

(NCT00982865)
Timeframe: Baseline up to 253 weeks

InterventionSubjects (Number)
MSC1936369B Regimen 110
MSC1936369B Regimen 2 (Without Food Effect + With Food Effect)14
MSC1936369B Regimen 3 Once Daily (QD)2
MSC1936369B Regimen 3 Twice Daily2

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. As AUCextra was >20% of AUC0-inf, t1/2 derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,
InterventionHours (h) (Geometric Mean)
C1D1C1D12
MSC1936369B 28 mg4.7816.750
MSC1936369B 3.5 mg3.3464.985
MSC1936369B 68 mg5.3356.926

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. As AUCextra was >20% of AUC0-inf, t1/2 derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,,,
InterventionHours (h) (Geometric Mean)
C1D1C1D12C3D1
MSC1936369B 120 mg5.2473.9643.038
MSC1936369B 14 mg4.5993.2362.811
MSC1936369B 45 mg5.3894.6882.931
MSC1936369B 7 mg3.4059.2492.959
MSC1936369B 94 mg5.3515.6722.842

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect)

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
InterventionHour (h) (Geometric Mean)
FastedFed
MSC1936369B 150 mg4.4526.123
MSC1936369B 90 mg4.8984.534

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect)

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. As AUCextra was >20% of AUC0-inf, t1/2 derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,
InterventionHours (h) (Geometric Mean)
C1D1C1D15
MSC1936369B 7 mg2.5942.335
MSC1936369B 14 mg5.1194.443
MSC1936369B 28 mg5.1156.646
MSC1936369B 45 mg4.1875.277

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect)

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. As AUCextra was >20% of AUC0-inf, t1/2 derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

InterventionHours (h) (Geometric Mean)
C1D15C3D1
MSC1936369B 5 mg2.9412.732

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect)

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. As AUCextra was >20% of AUC0-inf, t1/2 derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,
InterventionHours (h) (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 120 mg5.0574.8512.863
MSC1936369B 150 mg4.9045.4792.418
MSC1936369B 195 mg5.6416.0162.628
MSC1936369B 68 mg3.3056.4413.477
MSC1936369B 255 mg4.3134.8472.260
MSC1936369B 94 mg4.8265.1932.853

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
InterventionHour (h) (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 60 mg4.2365.2591.780
MSC1936369B 90 mg4.0975.5992.680

Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
InterventionHour (h) (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 45 mg2.0502.8903.144
MSC1936369B 60 mg2.5093.2652.636
MSC1936369B 75 mg2.8143.2103.260

Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect)

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
InterventionLiter (Geometric Mean)
FastedFed
MSC1936369B 150 mg288.1235.2
MSC1936369B 90 mg402.4393.6

Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect)

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. As AUCextra was >20% of AUC0-inf, Vz/F derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,
InterventionLiter (Geometric Mean)
C1D1C1D15
MSC1936369B 14 mg473.32555.9
MSC1936369B 28 mg319.40432.5
MSC1936369B 45 mg331.36378.0
MSC1936369B 7 mg339.58454.6

Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect)

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. As AUCextra was >20% of AUC0-inf, Vz/F derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

InterventionLiter (Geometric Mean)
C1D15C3D1
MSC1936369B 5 mg252.7352.10

Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect)

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. As AUCextra was >20% of AUC0-inf, Vz/F derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,
InterventionLiter (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 120 mg361.12646.9201.39
MSC1936369B 150 mg463.92642.1212.92
MSC1936369B 195 mg440.55464.2274.24
MSC1936369B 255 mg377.28295.1144.24
MSC1936369B 68 mg366.00406.6206.07
MSC1936369B 94 mg428.99385.6244.16

Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
InterventionLiter (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 60 mg292.61366.5137.0
MSC1936369B 90 mg336.38507.7292.5

Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
InterventionLiter (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 45 mg339.51297.9571.8
MSC1936369B 60 mg292.59315.0392.9
MSC1936369B 75 mg340.43437.6362.6

Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. As AUCextra was >20% of AUC0-inf, Vz/F derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,
InterventionLiter (Geometric Mean)
C1D1C1D12
MSC1936369B 28 mg336.32365.1
MSC1936369B 3.5 mg640.60507.8
MSC1936369B 68 mg307.90357.8

Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. As AUCextra was >20% of AUC0-inf, Vz/F derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,,,
InterventionLiter (Geometric Mean)
C1D1C1D12C3D1
MSC1936369B 120 mg361.99351.4316.63
MSC1936369B 14 mg396.76291.9422.04
MSC1936369B 45 mg378.56333.9348.19
MSC1936369B 7 mg561.27594.5928.91
MSC1936369B 94 mg389.49416.3438.91

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,
InterventionPercentage of AUC 0-∞ (Geometric Mean)
C1D1C1D12
MSC1936369B 1.5 mg42.2333.84
MSC1936369B 68 mg4.086.56

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,,,,,,,
InterventionPercentage of AUC 0-∞ (Geometric Mean)
C1D1C1D12C3D1
MSC1936369B 1 mg81.3350.6055.15
MSC1936369B 120 mg5.282.9726.05
MSC1936369B 14 mg5.317.8315.84
MSC1936369B 2.5 mg43.4540.6055.79
MSC1936369B 28 mg5.396.5728.06
MSC1936369B 3.5 mg26.8021.2732.85
MSC1936369B 45 mg3.528.1727.67
MSC1936369B 7 mg13.0819.8221.27
MSC1936369B 94 mg4.097.9416.54

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 2 (With Food Effect)

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: AUCextra = (1- [AUC0-t / AUC0-inf])*100. AUCextra was reported in terms of percentage of AUC0-inf. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
InterventionPercentage of AUC 0-∞ (Geometric Mean)
FastedFed
MSC1936369B 150 mg1.749.96
MSC1936369B 90 mg2.542.21

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 2 (Without Food Effect)

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

InterventionPercentage of AUC 0-∞ (Geometric Mean)
C1D15
MSC1936369B 1 mg40.86

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 2 (Without Food Effect)

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
InterventionPercentage of AUC 0-∞ (Geometric Mean)
C1D1C1D15
MSC1936369B 45 mg1.462.96
MSC1936369B 14 mg12.1712.45

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 2 (Without Food Effect)

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,,,,,,
InterventionPercentage of AUC 0-∞ (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 120 mg2.945.8216.22
MSC1936369B 150 mg2.644.8217.54
MSC1936369B 195 mg4.365.7723.45
MSC1936369B 2 mg55.7833.3433.93
MSC1936369B 255 mg3.575.2211.15
MSC1936369B 28 mg3.296.8926.32
MSC1936369B 3.5 mg31.6335.2933.77
MSC1936369B 5 mg27.2521.9317.27
MSC1936369B 68 mg2.665.0015.35
MSC1936369B 7 mg15.1019.4520.68
MSC1936369B 94 mg2.603.4018.02

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: AUCextra = (1- [AUC0-t / AUC0-inf])*100. AUCextra was reported in terms of percentage of AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
Interventionpercentage of AUC 0-∞ (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 60 mg1.887.959.11
MSC1936369B 90 mg2.114.2817.56

Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily

AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: AUCextra = (1- [AUC0-t / AUC0-inf])*100. AUCextra was reported in terms of percentage of AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
InterventionPercentage of AUC 0-∞ (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 45 mg16.8211.7830.63
MSC1936369B 60 mg7.7014.1416.43
MSC1936369B 75 mg10.9019.1921.34

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D12
MSC1936369B 1.5 mg6.29.4
MSC1936369B 68 mg1699.72108.2

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,,,,,,,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D12C3D1
MSC1936369B 1 mg136.238.315.4
MSC1936369B 120 mg2773.52022.83477.6
MSC1936369B 14 mg234.1206.3134.5
MSC1936369B 2.5 mg55.543.847.6
MSC1936369B 28 mg574.2805.6489.8
MSC1936369B 3.5 mg31.447.534.4
MSC1936369B 45 mg924.2960.71072.1
MSC1936369B 7 mg61.3105.655.5
MSC1936369B 94 mg1836.42257.61056.0

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect)

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
Interventionhour*ng/mL (Geometric Mean)
FastedFed
MSC1936369B 150 mg3344.35633.8
MSC1936369B 90 mg1580.61495.7

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect)

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

Interventionhour*ng/mL (Geometric Mean)
C1D15
MSC1936369B 1 mg15.7

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect)

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15
MSC1936369B 45 mg820.4933.9
MSC1936369B 14 mg218.4172.2

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect)

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,,,,,,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 120 mg2424.22129.02461.3
MSC1936369B 195 mg3602.23900.83452.9
MSC1936369B 2 mg23.433.315.4
MSC1936369B 255 mg4300.36232.15651.1
MSC1936369B 28 mg646.9669.1415.6
MSC1936369B 3.5 mg23.621.941.2
MSC1936369B 150 mg2287.82029.92796.2
MSC1936369B 5 mg59.1102.049.5
MSC1936369B 68 mg885.81665.21655.1
MSC1936369B 7 mg90.389.758.1
MSC1936369B 94 mg1525.61893.21584.8

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 60 mg1253.11753.91597.0
MSC1936369B 90 mg1581.41517.11400.3

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 45 mg527.6674.1696.0
MSC1936369B 60 mg742.31004.2700.8
MSC1936369B 75 mg939.9978.41285.7

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: : Regimen 2 (Without Food Effect)

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15
MSC1936369B 14 mg188.4161.5
MSC1936369B 45 mg808.0906.3

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: : Regimen 2 (Without Food Effect)

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,,,,,,,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 1 mg1.94.30.5
MSC1936369B 120 mg2287.01862.32053.6
MSC1936369B 150 mg2216.52086.62171.2
MSC1936369B 195 mg3415.63436.82484.5
MSC1936369B 2 mg8.222.210.2
MSC1936369B 255 mg4041.35765.94906.3
MSC1936369B 28 mg625.7621.2306.2
MSC1936369B 3.5 mg6.713.826.2
MSC1936369B 5 mg67.979.340.5
MSC1936369B 68 mg861.11553.91394.7
MSC1936369B 7 mg74.467.846.1
MSC1936369B 94 mg1484.61826.21299.3

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 1

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

Interventionhour*nanogram per milliliter (h*ng/mL) (Geometric Mean)
C1D1C1D12
MSC1936369B 68 mg1624.81900.3

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 1

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,,,,,,,,
Interventionhour*nanogram per milliliter (h*ng/mL) (Geometric Mean)
C1D1C1D12C3D1
MSC1936369B 1.5 mg5.26.02.7
MSC1936369B 120 mg2292.41682.42064.1
MSC1936369B 14 mg213.9182.0113.2
MSC1936369B 2.5 mg18.526.021.0
MSC1936369B 28 mg531.3691.9334.9
MSC1936369B 3.5 mg22.735.923.0
MSC1936369B 45 mg889.0880.0666.3
MSC1936369B 1 mg4.67.06.9
MSC1936369B 7 mg52.783.645.2
MSC1936369B 94 mg1748.11991.4876.7

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 2 (With Food Effect)

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
Interventionhour*ng/mL (Geometric Mean)
FastedFed
MSC1936369B 150 mg32865072.9
MSC1936369B 90 mg1509.61458.3

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 3 Once Daily

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 60 mg1229.31532.41392.3
MSC1936369B 90 mg1544.91428.81122.5

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 3 Twice Daily

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
Interventionhour*ng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 45 mg407.2589.3450.0
MSC1936369B 60 mg681.4838.8577.0
MSC1936369B 75 mg791.1710.31005.0

Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1

Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours (h) post-dose on Cycle 1(C1) Day 1 (D1), Cycle 1 Day 12 (D12) and Cycle 3 (C3) Day 1

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
C1D1C1D12
MSC1936369B 68 mg357.39413.58

Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1

Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours (h) post-dose on Cycle 1(C1) Day 1 (D1), Cycle 1 Day 12 (D12) and Cycle 3 (C3) Day 1

,,,,,,,,,
Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
C1D1C1D12C3D1
MSC1936369B 1 mg2.022.922.00
MSC1936369B 1.5 mg3.202.692.90
MSC1936369B 120 mg428.85425.26652.70
MSC1936369B 14 mg62.3254.4751.30
MSC1936369B 2.5 mg4.216.295.60
MSC1936369B 28 mg126.21150.6784.70
MSC1936369B 3.5 mg6.699.758.06
MSC1936369B 45 mg212.96175.94167.75
MSC1936369B 7 mg12.6021.9310.90
MSC1936369B 94 mg325.99602.12282.44

Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect)

Cmax was obtained directly from the concentration versus time curve. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
Interventionng/mL (Geometric Mean)
FastedFed
MSC1936369B 150 mg1158.00370.70
MSC1936369B 90 mg321.14305.94

Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect)

Cmax was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
Interventionng/mL (Geometric Mean)
C1D1C1D15
MSC1936369B 14 mg39.1934.87
MSC1936369B 45 mg321.85286.88

Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect)

Cmax was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,,,,,,,
Interventionng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 120 mg605.11492.81568.49
MSC1936369B 150 mg539.02450.29795.86
MSC1936369B 195 mg680.87629.85773.14
MSC1936369B 2 mg2.877.774.30
MSC1936369B 255 mg990.921535.602344.91
MSC1936369B 28 mg187.98131.7196.60
MSC1936369B 3.5 mg4.554.216.56
MSC1936369B 1 mg1.652.281.25
MSC1936369B 5 mg17.2618.7814.81
MSC1936369B 68 mg306.63539.17710.94
MSC1936369B 7 mg30.9018.4716.10
MSC1936369B 94 mg373.59432.46532.80

Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily

Cmax was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
Interventionng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 60 mg241.27316.08473.27
MSC1936369B 90 mg402.77324.80376.62

Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily

Cmax was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
Interventionng/mL (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 45 mg132.57178.09139.60
MSC1936369B 60 mg206.46231.12157.46
MSC1936369B 75 mg263.08190.42329.28

Number of Subjects With Clinical Benefit (Complete Response [CR], Partial Response [PR] or Stable Disease [SD}) and Progressive Disease (PD) Based on the Best Overall Response (BOR)

Number of subjects with clinical benefit (CR, PR, or SD) and PD according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) was reported. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: defined as at least a 30% decrease in sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD:defined as at least a 20% increase in sum of longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of longest diameter while on study. (NCT00982865)
Timeframe: Baseline until disease progression (assessed up to end of treatment [253 weeks])

,,,
InterventionSubjects (Number)
CRPRSDPD
MSC1936369B Regimen 1001920
MSC1936369B Regimen 2 and Regimen 2 Food Effect043433
MSC1936369B Regimen 3 Once Daily (QD)0294
MSC1936369B Regimen 3 Twice Daily161412

Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events

Any clinically significant changes in laboratory evaluations and vital signs were recorded as treatment emergent adverse events. The clinical laboratory parameters that were assessed included: Hematological parameters, Blood chemistry parameters, Urinalysis and the vital signs that were assessed included: Blood pressure, Heart rate, Temperature and Weight. SAF analysis was used. (NCT00982865)
Timeframe: Baseline up to 253 weeks

,,,
InterventionSubjects (Number)
Haemoglobin decreasedAnaemiaLymphopeniaThrombocytopeniaPlatelet count decreasedNeutropeniaLeukopeniaPancytopeniaHyponatraemiaHypokalaemiaHyperkalaemiaHypocalcaemiaHypercalcaemiaHypomagnesaemiaHypophosphataemiaHepatic enzyme increasedHepatic function abnormalAlanine aminotransferase increasedAspartate aminotransferase increasedBlood alkaline phosphatase increasedHyperbilirubinaemiaBlood lactate dehydrogenase increasedBlood creatine phosphokinase increasedBlood creatinine increasedBlood 25-hydroxycholecalciferol decreasedVitamin D decreasedBlood parathyroid hormone increasedHyperglycaemiaC-reactive protein increasedProteinuriaHyperthyroidismHypoalbuminaemiaWeight increasedWeight decreasedHyperthermiaHypertensionHypotensionHeart rate increasedTachycardiaBlood potassium increased
MSC1936369B Regimen 111033000004120200001111101010000306173131
MSC1936369B Regimen 2 (Without Food Effect + With Food Effect)223761400110073321111010211111100438551000
MSC1936369B Regimen 3 Once Daily (QD)0302001002000200000000100000010004012020
MSC1936369B Regimen 3 Twice Daily0301010112010000022101500000011232140000

Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation

AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 253 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs. (NCT00982865)
Timeframe: Baseline up to 253 weeks

,,,
InterventionSubjects (Number)
TEAEsSerious TEAEsTEAEs leading to discontinuation
MSC1936369B Regimen 1472313
MSC1936369B Regimen 2 (Without Food Effect + With Food Effect)824522
MSC1936369B Regimen 3 Once Daily (QD)1582
MSC1936369B Regimen 3 Twice Daily34216

Phosphorylated Extra-Cellular Signal-Regulated Kinase (pERK) Fold Change in Peripheral Blood Monocyte Cells (PBMC) and Tot ERK Fold Change in Peripheral Blood Monocyte Cells (PBMC)

(NCT00982865)
Timeframe: Pre-dose on C1D1, C1D2, C1D5, C1D8; 2, 4, 8 h post-dose on C1D1; pre-dose, 2, 8, 24 h post-dose on C1D12-15; pre-dose, 2, 4 h post-dose on C1D3

,
Interventionfold change (Mean)
C1D1, Pre-dose (pERK)C1D1, 2 h post-dose (pERK)C1D1, 8 h post-dose (pERK)C1D2, Pre-dose (pERK)C1D8, Pre-dose (pERK)C1D12-15, Pre-dose (pERK)C1D12-15, 2 h Post-dose (pERK)C1D12-15, 8 h Post-dose (pERK)C1D12-15, 24 h Post-dose (pERK)C1D1, Pre-dose (Tot ERK)C1D1, 2 h post-dose (Tot ERK)C1D1, 8 h post-dose (Tot ERK)C1D2, Pre-dose (Tot ERK)C1D8, Pre-dose (Tot ERK)C1D12-15, Pre-dose (Tot ERK)C1D12-15, 2 h Post-dose (Tot ERK)C1D12-15, 8 h Post-dose (Tot ERK)C1D12-15, 24 h Post-dose (Tot ERK)
MSC1936369B Regimen 3 Once Daily4.1211.1781.8783.0812.5413.2411.4711.9022.5981.021.0781.0781.0130.9441.3331.3351.0441.048
MSC1936369B Regimen 3 Twice Daily3.6291.2491.8212.0692.2352.161.3151.982.0431.0861.0791.0981.1081.0491.0471.0591.0261.068

Phosphorylated Extra-Cellular Signal-Regulated Kinase (pERK) Fold Change in Peripheral Blood Monocyte Cells (PBMC) and Tot ERK Fold Change in Peripheral Blood Monocyte Cells (PBMC)

(NCT00982865)
Timeframe: Pre-dose on C1D1, C1D2, C1D5, C1D8; 2, 4, 8 h post-dose on C1D1; pre-dose, 2, 8, 24 h post-dose on C1D12-15; pre-dose, 2, 4 h post-dose on C1D3

Interventionfold change (Mean)
C1D1, Pre-dose (pERK)C1D1, 2 h post-dose (pERK)C1D1, 4 h post-dose (pERK)C1D1, 8 h post-dose (pERK)C1D2, Pre-dose (pERK)C1D8, Pre-dose (pERK)C1D12-15, Pre-dose (pERK)C1D12-15, 2 h Post-dose (pERK)C1D12-15, 8 h Post-dose (pERK)C1D12-15, 24 h Post-dose (pERK)C3D1, Pre-dose (pERK)C3D1, 2 h Post-dose (pERK)C3D1, 4 h Post-dose (pERK)C1D1, Pre-dose (Tot ERK)C1D1, 2 h post-dose (Tot ERK)C1D1, 4 h post-dose (Tot ERK)C1D1, 8 h post-dose (Tot ERK)C1D2, Pre-dose (Tot ERK)C1D8, Pre-dose (Tot ERK)C1D12-15, Pre-dose (Tot ERK)C1D12-15, 2 h Post-dose (Tot ERK)C1D12-15, 8 h Post-dose (Tot ERK)C1D12-15, 24 h Post-dose (Tot ERK)C3D1, Pre-dose (Tot ERK)C3D1, 2 h Post-dose (Tot ERK)C3D1, 4 h Post-dose (Tot ERK)
MSC1936369B Regimen 2 (Without Food Effect + With Food Effect)3.9371.3053.4221.4542.4112.8683.2651.2931.6532.4763.7161.2882.6881.0751.0691.0121.0951.131.1081.1181.1251.0411.0451.1381.2511.052

Phosphorylated Extra-Cellular Signal-Regulated Kinase (pERK) Fold Change in Peripheral Blood Monocyte Cells (PBMC) and Tot ERK Fold Change in Peripheral Blood Monocyte Cells (PBMC)

(NCT00982865)
Timeframe: Pre-dose on C1D1, C1D2, C1D5, C1D8; 2, 4, 8 h post-dose on C1D1; pre-dose, 2, 8, 24 h post-dose on C1D12-15; pre-dose, 2, 4 h post-dose on C1D3

Interventionfold change (Mean)
C1D1, Pre-dose (pERK)C1D1, 2 h post-dose (pERK)C1D1, 4 h post-dose (pERK)C1D1, 8 h post-dose (pERK)C1D2, Pre-dose (pERK)C1D5, Pre-dose (pERK)C1D8, Pre-dose (pERK)C1D12-15, Pre-dose (pERK)C1D12-15, 2 h Post-dose (pERK)C1D12-15, 8 h Post-dose (pERK)C1D12-15, 24 h Post-dose (pERK)C3D1, Pre-dose (pERK)C3D1, 2 h Post-dose (pERK)C3D1, 4 h Post-dose (pERK)C1D1, Pre-dose (Tot ERK)C1D1, 2 h post-dose (Tot ERK)C1D1, 4 h post-dose (Tot ERK)C1D1, 8 h post-dose (Tot ERK)C1D2, Pre-dose (Tot ERK)C1D5, Pre-dose (Tot ERK)C1D8, Pre-dose (Tot ERK)C1D12-15, Pre-dose (Tot ERK)C1D12-15, 2 h Post-dose (Tot ERK)C1D12-15, 8 h Post-dose (Tot ERK)C1D12-15, 24 h Post-dose (Tot ERK)C3D1, Pre-dose (Tot ERK)C3D1, 2 h Post-dose (Tot ERK)C3D1, 4 h Post-dose (Tot ERK)
MSC1936369B Regimen 14.5241.2353.8281.4542.8532.7224.483.2571.2521.5142.7685.1791.7953.1061.11.0631.0591.0581.0751.1631.2331.2231.040.9941.0471.0741.0870.674

Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

InterventionHours (h) (Median)
C1D1C1D12
MSC1936369B 68 mg1.0001.000

Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,,,,,,,,
InterventionHours (h) (Median)
C1D1C1D12C3D1
MSC1936369B 1 mg1.5001.6331.52
MSC1936369B 1.5 mg0.7500.5330.500
MSC1936369B 120 mg1.0171.0832.000
MSC1936369B 14 mg1.0001.5001.500
MSC1936369B 2.5 mg1.5001.0001.52
MSC1936369B 28 mg1.5001.0001.000
MSC1936369B 3.5 mg1.5001.0001.000
MSC1936369B 45 mg1.0172.0001.508
MSC1936369B 7 mg1.5001.0171.517
MSC1936369B 94 mg1.4831.5001.767

Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect)

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
InterventionHours (h) (Median)
FastedFed
MSC1936369B 150 mg1.0006.000
MSC1936369B 90 mg1.6002.033

Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect)

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
InterventionHours (h) (Median)
C1D1C1D15
MSC1936369B 14 mg1.5001.500
MSC1936369B 45 mg0.5001.500

Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect)

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,,,,,,,
InterventionHours (h) (Median)
C1D1C1D15C3D1
MSC1936369B 1 mg1.5001.5001.250
MSC1936369B 120 mg1.2502.0001.042
MSC1936369B 150 mg1.5001.5171.333
MSC1936369B 195 mg1.2501.2501.000
MSC1936369B 2 mg1.0170.9672.000
MSC1936369B 255 mg2.0001.4581.000
MSC1936369B 28 mg1.0001.0171.50
MSC1936369B 3.5 mg1.5002.0001.258
MSC1936369B 5 mg1.0000.6671.000
MSC1936369B 68 mg1.0001.2500.500
MSC1936369B 7 mg0.5331.0082.500
MSC1936369B 94 mg1.5001.5002.000

Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
InterventionHours (h) (Median)
C1D1C1D15C3D1
MSC1936369B 60 mg1.0332.5002.000
MSC1936369B 90 mg1.5001.4921.000

Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
InterventionHours (h) (Median)
C1D1C1D15C3D1
MSC1936369B 45 mg1.5001.5001.467
MSC1936369B 60 mg1.0001.5001.183
MSC1936369B 75 mg0.6671.5001.467

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. As AUCextra was >20% of AUC0-inf, CL/f derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,
InterventionLiter per hour (Geometric Mean)
C1D1C1D12
MSC1936369B 28 mg48.7637.49
MSC1936369B 3.5 mg132.6970.60
MSC1936369B 68 mg40.0135.80

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. As AUCextra was >20% of AUC0-inf, CL/f derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1

,,,,
InterventionLiter per hour (Geometric Mean)
C1D1C1D12C3D1
MSC1936369B 120 mg47.8261.4472.25
MSC1936369B 14 mg59.8062.53104.07
MSC1936369B 45 mg48.6949.3782.35
MSC1936369B 7 mg114.2644.55217.56
MSC1936369B 94 mg50.4550.88107.06

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect)

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. Summarized data over Day 1 and Day 2 was reported. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2

,
InterventionLiter per hour (Geometric Mean)
FastedFed
MSC1936369B 150 mg44.8526.62
MSC1936369B 90 mg56.9460.17

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect)

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. As AUCextra was >20% of AUC0-inf, CL/f derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,
InterventionLiter per hour (Geometric Mean)
C1D1C1D15
MSC1936369B 14 mg64.0986.72
MSC1936369B 28 mg43.2845.10
MSC1936369B 45 mg54.8549.65
MSC1936369B 7 mg90.76134.9

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect)

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. As AUCextra was >20% of AUC0-inf, CL/f derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

InterventionLiter per hour (Geometric Mean)
C1D15C3D1
MSC1936369B 5 mg59.5589.34

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect)

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. As AUCextra was >20% of AUC0-inf, CL/f derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,,,,,
InterventionLiter per hour (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 120 mg49.5092.4248.76
MSC1936369B 150 mg65.5781.2261.04
MSC1936369B 195 mg54.1353.4972.33
MSC1936369B 255 mg60.6342.2044.23
MSC1936369B 68 mg76.7743.7641.08
MSC1936369B 94 mg61.6151.4759.31

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

,
InterventionLiter per hour (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 60 mg47.8848.3153.36
MSC1936369B 90 mg56.9162.8575.63

Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. (NCT00982865)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1

,,
InterventionLiter per hour (Geometric Mean)
C1D1C1D15C3D1
MSC1936369B 45 mg114.8271.44126.1
MSC1936369B 60 mg80.8366.89103.3
MSC1936369B 75 mg83.8694.4877.09

Response

"Clinical biologic activity of treatment, defined as the sum of complete response, partial response, and prolonged stable disease for ≥ 16 weeks, upon treatment with the combination of sorafenib and bevacizumab, in patients with advanced metastatic melanoma previously treated with immunotherapy or in previously untreated patients who are not appropriate candidates to receive IL-2-based treatment.~Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started of the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started." (NCT00387751)
Timeframe: 4 months

Interventionparticipants (Number)
Bevacizumab and Sorafenib11

Duration of Complete Response

Duration of complete response was the number of days from the date that a complete response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes). (NCT00492297)
Timeframe: from confirmed CR until PD (median 259 days)

Interventiondays (Number)
Sorafenib + Dacarbazine420

Duration of Partial Response

Duration of partial response was the number of days from the date that a partial response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes). (NCT00492297)
Timeframe: from confirmed PR until PD (median 259 days)

Interventiondays (Median)
Sorafenib + Dacarbazine255

Duration of Response

Duration of Response was assessed in subjects who showed a Partial Response (PR) or Complete Response (CR). It was defined as the time from the first documented objective response to Progressive Disease (PD), or death if before documented progression. Duration of response for subjects who have not progressed or died at the time of analysis was censored at the date of last tumor assessment. (NCT00492297)
Timeframe: from confirmed Complete Response (CR) or Partial Response (PR) until Progressive Disease (PD) (median 259 days)

Interventiondays (Median)
Sorafenib + Dacarbazine327

Duration of Stable Disease

Duration of Stable Disease (DSD), defined as the time from the first documented objective evidence of Stable Disease (SD) to disease progression (DP) or death if death occurred before DP, was assessed in subjects who showed SD as best response. DSD for subjects who had not progressed or died was censored at the date of last tumor assessment. (NCT00492297)
Timeframe: from start of therapy to PD, only in non-responders (median 259 days)

Interventiondays (Median)
Sorafenib + Dacarbazine93

Overall Survival

Overall Survival was the number of days from the date that combination treatment started until the date of death. (NCT00492297)
Timeframe: from start of treatment until death (median 259 days)

Interventiondays (Median)
Sorafenib + Dacarbazine259

Progression-free Survival

Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation. (NCT00492297)
Timeframe: from start of treatment until progression or death before progression (median 259 days)

Interventiondays (Median)
Sorafenib + Dacarbazine102

Time to Progression

Time to Progression was the number of days from the start of therapy to progression (if patient progressed then censored=no) or to the last observation at which the patient was known to have not progressed, that is, the last observation with a best response of CR, PR, or SD. (NCT00492297)
Timeframe: From start of treatment until progression (median 259 days)

Interventiondays (Median)
Sorafenib + Dacarbazine102

Time to Response

Time to Response in subjects who achieved an objective response (PR or CR with confirmation) was measured from the date of starting study combination treatment until the earliest date that the response was first documented. (NCT00492297)
Timeframe: start of therapy to confirmed CR or PR (median 259 days)

Interventiondays (Median)
Sorafenib + Dacarbazine48

Disease Control (DC)

DC was defined as the total number of subjects whose best response was not progressive disease (PD) (total number of CRs + total number of PRs + total number of Stable Diseases (SD)). The DC at specific time points could also be calculated as the total number of subjects whose response was not PD at that time point. (NCT00492297)
Timeframe: after start of treatment, at 6 months and 12 months

Interventionparticipants (Number)
DC based on overall best responseDC at 6 monthsDC at 12 months
Sorafenib + Dacarbazine413838

Overall Best Response

Best Overall Response (BOR): Best tumor response achieved during or within 30 days after active therapy confirmed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR): The disappearance of all target and non-target lesions. Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD was defined as steady state of disease, PD was defined as an increase of at least 20% increase in the sum of the LD of target lesions or appearance of new lesions. (NCT00492297)
Timeframe: during or within 30 days after active therapy

Interventionparticipants (Number)
Overall response (CR+PR)Complete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)
Sorafenib + Dacarbazine10193134

Percentage of Subjects With Progression-free Survival at Specific Time-points

Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation. (NCT00492297)
Timeframe: from start of treatment until progression or death before progression after 3, 6 and 12 months

Interventionpercentage of participants (Number)
PFS at month 3PFS at month 6PFS at month 12
Sorafenib + Dacarbazine56.6333.7310.84

6-month Progression-free Survival

Measured from the date of registration to the first of progression or death due to any cause with patients last known to be alive and progression-free censored at the date of last contact (NCT00329641)
Timeframe: Every 6 weeks for the first 8 cycles of therapy, and then every 9 weeks until disease progression for up to 3 years after registration or until death

InterventionPercent of population (Number)
Sorafenib, Carboplatin, Paclitaxel29

One-year Overall Survival

Measured from date of registration to study until death due to any caused with observations last known to be alive censored at the date of last contact (NCT00329641)
Timeframe: Every 6-9 weeks until progression, after progression every six months for first two years and annually thereafter up to 3 for up to 3 years after registration or until death

InterventionPercentage of population (Number)
Sorafenib, Carboplatin, Paclitaxel42

Response Rate (Complete and Partial Response)

Complete response corresponds to complete disappearance of all measurable and non-measurable lesions with no new lesions. Partial response corresponds to greater than or equal to 30fi decrease of sum of longest diameter of all target measurable lesions with no new lesion and non unequivocal progression of non-measurable disease. (NCT00329641)
Timeframe: Every 6 weeks for the first 8 cycles of therapy, then every three cycles (9 weeks) until progression

Interventionparticipants (Number)
Sorafenib, Carboplatin, Paclitaxel0

Toxicity

Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event (NCT00329641)
Timeframe: Weekly during the first cycle of therapy, then prior to each cycle (one cycle = 3 weeks)

InterventionParticipants with a given type of AE (Number)
Calcium, serum-low (hypocalcemia)CataractDiarrheaFatigue (asthenia, lethargy, malaise)Febrile neutropeniaHemoglobinInfec w/ Gr 3/4 neut-Urinary tractLeukocytes (total WBC)LymphopeniaMucositis/stomatitis (func/symp) - PharynxNeuropathy: sensoryNeutrophils/granulocytes (ANC/AGC)PlateletsPruritus/itchingRash/desquamationVision-blurred vision
Intervention11211214212104151

Objective Response (Complete and Partial Response) Rate

Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Objective response =complete response (CR) + partial response (PR). Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of longest diameters. (NCT00110019)
Timeframe: Tumor response was assessed after every 2 cycles during cycle 1 through 10. After cycle 10, tumor response was assessed after every 3 cycles.

Interventionproportion (Number)
Arm I (Carboplatin + Paclitaxel + Sorafenib)0.205
Arm II (Carboplatin + Paclitaxel+Placebo)0.182

Overall Survival

Overall survival is defined as time from study entry to death from any cause. The comparison of overall survival was conducted in intention-to-treat population. (NCT00110019)
Timeframe: Survival was assessed every 3 months if patient is < 2 years from study entry. Every 6 months is patient is 2-5 years from study entry.

Interventionmonths (Median)
Arm I (Carboplatin + Paclitaxel + Sorafenib)11.1
Arm II (Carboplatin + Paclitaxel+Placebo)11.3

Progression-free Survival

Progression-free survival was defined as time from study entry to disease progression or death from any cause, whichever occurred first. Patients without disease progression were censored at last date of assessment. Disease progression was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. (NCT00110019)
Timeframe: Tumor response was assessed after every 2 cycles during cycle 1 through 10, and every 3 cycles after cycle 10. Survival was assessed every 3 months if patient is < 2 years from study entry, and every 6 months if 2-5 years from study entry.

Interventionmonths (Median)
Arm I (Carboplatin + Paclitaxel + Sorafenib)4.9
Arm II (Carboplatin + Paclitaxel+Placebo)4.2

Complete Response

Analysis of the Primary Endpoint: The complete responses will be estimated by the number of patients with CR divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 4 cycles

InterventionPercentage of Participants (Number)
FCR With Lenalidomide45

Overall Response Rate

Analysis of the other Secondary Endpoints: The overall response rate will be estimated by the number of patients with complete and partial responses divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 6 cycles

InterventionPercentage of Participants (Number)
FCR With Lenalidomide95

Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment

European Quality of Life 5-dimensional (EQ-5D) is a self-administered questionnaire developed to measure health status across 5 dimensions: Mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). The five dimensions are summarized into a single score, the EQ-5D index score, which ranges between 0 and 1, with 0 representing the worst imaginable health state or death and 1 representing perfect health. (NCT00110994)
Timeframe: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days

Interventionscores on a scale (Mean)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine-0.015
Placebo + Dacarbazine-0.019

Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the Visit at Which Best Response Was First Noted

European Quality of Life 5-dimensional (EQ-5D) is a self-administered questionnaire developed to measure health status across 5 dimensions: Mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). The five dimensions are summarized into a single score, the EQ-5D index score, which ranges between 0 and 1, with 0 representing the worst imaginable health state or death and 1 representing perfect health. (NCT00110994)
Timeframe: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days

Interventionscores on a scale (Mean)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine-0.004
Placebo + Dacarbazine-0.008

Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the End of Treatment

European Quality of Life Visual Analogue Scale (EQ-VAS) is a self-administered test that records the respondents' self-rated health status on a visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Responders specify their scales by indicating a position along a continuous line between 0 and 100. (NCT00110994)
Timeframe: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days

Interventionscores on a scale (Mean)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine-2.00
Placebo + Dacarbazine-8.146

Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the Visit at Which Best Response Was First Noted

European Quality of Life Visual Analogue Scale (EQ-VAS) is a self-administered test that records the respondents' self-rated health status on a visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Responders specify their scales by indicating a position along a continuous line between 0 and 100. (NCT00110994)
Timeframe: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days

Interventionscores on a scale (Mean)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine0.558
Placebo + Dacarbazine-4.425

Duration of Response (DOR)

Duration of response was defined as the time from the first documented objective response of Partial Response (PR: At least a 30% decrease in the sum of the longest diameter [SLD] of target lesions, taking as reference the baseline SLD or better) or Complete Response (CR: Disappearance of all target lesions), whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. (NCT00110994)
Timeframe: Time from initial response to documented tumor progression or death (median time of 188 days)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine188
Placebo + Dacarbazine161

Overall Survival (OS)

Overall Survival (OS) was calculated as the number of days from date of randomization to death date. Subjects who had not died at the time of analysis were censored at their last contact date. (NCT00110994)
Timeframe: Time from randomization to death (the maximum treatment duration of 71.1 weeks)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine319
Placebo + Dacarbazine359

Progression Free Survival (PFS)

PFS was calculated as the time (days) from date of randomization to date of first observed DP (per modified Response Evaluation Criteria In Solid Tumors [RECIST] or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease) or death due to any cause, if death occurred before progression was documented. The actual date of tumor assessments was used for this calculation. PFS for subjects without progression or death was censored at the last date of tumor evaluation. PFS for subjects who had no tumor assessments after baseline and did not die was censored at 1 day. (NCT00110994)
Timeframe: Time from randomization to documented tumor progression or death (the maximum treatment duration of 71.1 weeks)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine148
Placebo + Dacarbazine82

Time to Progression (TTP)

TTP was calculated as the time (days) from date of randomization to date of first observed disease progression (per modified RECIST or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease). The actual dates of tumor assessments were used for this calculation. TTP for subjects without disease progression at the time of analysis, including subjects with death prior to progression, was censored at the last date of tumor evaluation. TTP for subjects who had no tumor assessments after baseline was censored at 1 day. (NCT00110994)
Timeframe: Time from randomization to documented tumor progression (median time of 148 days)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine148
Placebo + Dacarbazine82

Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to the Visit When the Best Tumor Response Was Noted

Change in ECOG PS is defined as an improvement (increase) or worsening (decrease) of at least one grade from the baseline ECOG score (from 0 [fully active] to 5 [dead]). Change in ECOG PS was recorded at the visit at which best confirmed response (BCR) using the modified RECIST (PR, CR, stable disease or Progressive Disease (PD)) was first noted (the change was 7% for both Sorafenib and Placebo). The BCR is the BCR recorded from the start of the treatment until DP/recurrence (taking as reference for DP, the smallest measurements recorded since treatment started). (NCT00110994)
Timeframe: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days

,
Interventionparticipants (Number)
missingbetterno changeworse
Placebo + Dacarbazine123413
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine113415

Number of Participants in Tumor Response Categories

Tumor response was defined as the best response (confirmed complete response [CR], partial response [PR], stable disease [SD], or progressive disease [PD]) assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). PR: At least a 30% decrease in the sum of the longest diameter [SLD] of target lesions, taking as reference the baseline SLD. CR: Disappearance of all target lesions. SD: Does not qualify for CR or PR. PD: at least a 20% increase in SLD taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. (NCT00110994)
Timeframe: Every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days

,
Interventionparticipants (Number)
CRPRSDPDNot Evaluated
Placebo + Dacarbazine0622211
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine01224150

Reviews

15 reviews available for niacinamide and Melanoma

ArticleYear
Nicotinamide for skin cancer chemoprevention.
    The Australasian journal of dermatology, 2017, Volume: 58, Issue:3

    Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; DNA Repair; Humans; Immune Tolerance; Keratosis, Ac

2017
Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma.
    Cancer, 2017, 06-01, Volume: 123, Issue:S11

    Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Com

2017
Melanoma and nonmelanoma skin cancer chemoprevention: A role for nicotinamide?
    Photodermatology, photoimmunology & photomedicine, 2018, Volume: 34, Issue:1

    Topics: Animals; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; DNA Repair; Humans; Immunomodulation; Mela

2018
Mechanism and consequences of RAF kinase activation by small-molecule inhibitors.
    British journal of cancer, 2014, Aug-12, Volume: 111, Issue:4

    Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Enzyme Activation; Humans; Indoles; Melano

2014
Ocular Toxicity in Metastatic Melanoma Patients Treated With Mitogen-Activated Protein Kinase Kinase Inhibitors: A Case Series.
    American journal of ophthalmology, 2015, Volume: 160, Issue:5

    Topics: Aged; Female; Humans; Male; Melanoma; Melanoma, Cutaneous Malignant; Middle Aged; Mitogen-Activated

2015
[New molecular target therapy for thyroid neoplasms and malignant melanomas].
    Nihon Jibiinkoka Gakkai kaiho, 2015, Volume: 118, Issue:11

    Topics: Antibodies, Monoclonal; Antineoplastic Agents; Clinical Trials as Topic; Humans; Indoles; Ipilimumab

2015
Metastatic melanoma: scientific rationale for sorafenib treatment and clinical results.
    Onkologie, 2008, Volume: 31, Issue:7

    Topics: Antineoplastic Agents; Benzenesulfonates; Clinical Trials as Topic; Evidence-Based Medicine; Humans;

2008
BRAF signaling and targeted therapies in melanoma.
    Hematology/oncology clinics of North America, 2009, Volume: 23, Issue:3

    Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; C

2009
BRAF as therapeutic target in melanoma.
    Biochemical pharmacology, 2010, Sep-01, Volume: 80, Issue:5

    Topics: Antineoplastic Agents; Benzenesulfonates; Humans; Melanoma; Niacinamide; Phenylurea Compounds; Proto

2010
Does basal cell carcinoma belong to the spectrum of sorafenib-induced epithelial skin cancers?
    Dermatology (Basel, Switzerland), 2010, Volume: 221, Issue:3

    Topics: Aged; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Basal Cell; Carcinoma, Renal Cell; Female

2010
Sorafenib in melanoma.
    Expert opinion on investigational drugs, 2012, Volume: 21, Issue:4

    Topics: Animals; Benzenesulfonates; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Melanoma

2012
Sorafenib.
    Expert opinion on pharmacotherapy, 2006, Volume: 7, Issue:4

    Topics: Animals; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Carcinoma, Renal Cell;

2006
Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway.
    Seminars in oncology, 2006, Volume: 33, Issue:4

    Topics: Animals; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Renal Cell; Cell Transformation, Neopl

2006
[Clinical studies with sorafenib (Nexavar) in metastatic melanoma].
    Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 2007, Volume: 5, Issue:4

    Topics: Antineoplastic Agents; Benzenesulfonates; Clinical Trials as Topic; Humans; Melanoma; Niacinamide; P

2007
Sorafenib: delivering a targeted drug to the right targets.
    Expert review of anticancer therapy, 2007, Volume: 7, Issue:5

    Topics: Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Clinical

2007

Trials

26 trials available for niacinamide and Melanoma

ArticleYear
Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial.
    Targeted oncology, 2021, Volume: 16, Issue:1

    Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Melanoma; Middle Aged; Niacinamide; Protein Ki

2021
Correlation of changes in HIF-1α and p53 expressions with vitamin B3 deficiency in skin cancer patients.
    Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia, 2019, Volume: 154, Issue:5

    Topics: Administration, Oral; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, al

2019
Pimasertib-associated ophthalmological adverse events.
    Acta ophthalmologica, 2018, Volume: 96, Issue:7

    Topics: Aged; Antineoplastic Agents; Color Perception Tests; Cross-Sectional Studies; Drug-Related Side Effe

2018
Cutaneous side effects of combined therapy with sorafenib and pegylated interferon alpha-2b in metastatic melanoma (phase II DeCOG trial).
    Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 2013, Volume: 11, Issue:9

    Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Causality; Comorbidity; Drug Eruptions; Female

2013
Regulation of CD4(+)NKG2D(+) Th1 cells in patients with metastatic melanoma treated with sorafenib: role of IL-15Rα and NKG2D triggering.
    Cancer research, 2014, Jan-01, Volume: 74, Issue:1

    Topics: Adult; Aged; CD4 Antigens; Cell Growth Processes; Female; Humans; Interleukin-15; Interleukin-15 Rec

2014
A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma.
    Journal of immunotherapy (Hagerstown, Md. : 1997), 2014, Volume: 37, Issue:3

    Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Female; Humans;

2014
Correlation of somatic mutations and clinical outcome in melanoma patients treated with Carboplatin, Paclitaxel, and sorafenib.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2014, Jun-15, Volume: 20, Issue:12

    Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Double-Blind

2014
Phase II study evaluating the efficacy, safety, and pharmacodynamic correlative study of dual antiangiogenic inhibition using bevacizumab in combination with sorafenib in patients with advanced malignant melanoma.
    Cancer chemotherapy and pharmacology, 2014, Volume: 74, Issue:1

    Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Pro

2014
A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma.
    The oncologist, 2015, Volume: 20, Issue:6

    Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Disease-Free Survival; Dose

2015
Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2016, Jan-15, Volume: 22, Issue:2

    Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; DNA Copy Number

2016
Sorafenib in metastatic uveal melanoma: efficacy, toxicity and health-related quality of life in a multicentre phase II study.
    British journal of cancer, 2016, Jun-28, Volume: 115, Issue:1

    Topics: Aged; Antineoplastic Agents; Disease-Free Survival; Female; Humans; Male; Melanoma; Niacinamide; Phe

2016
Expression of sorafenib targets in melanoma patients treated with carboplatin, paclitaxel and sorafenib.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2009, Feb-01, Volume: 15, Issue:3

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Carboplatin; Cell Line, Tumor; Di

2009
Safety, efficacy, pharmacokinetics, and pharmacodynamics of the combination of sorafenib and tanespimycin.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2010, Jul-15, Volume: 16, Issue:14

    Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Benzoquinones; Clini

2010
A phase II trial of sorafenib in metastatic melanoma with tissue correlates.
    PloS one, 2010, Dec-29, Volume: 5, Issue:12

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Benzenesulfonates; Cyclin D1; DNA Mutational

2010
Sorafenib and pegylated interferon-α2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial.
    Annals of oncology : official journal of the European Society for Medical Oncology, 2011, Volume: 22, Issue:7

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocol

2011
Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study.
    Cancer chemotherapy and pharmacology, 2011, Volume: 68, Issue:5

    Topics: Antineoplastic Agents; Area Under Curve; Benzenesulfonates; Cytochrome P-450 Enzyme System; Dextrome

2011
Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies.
    British journal of cancer, 2011, Jul-26, Volume: 105, Issue:3

    Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Dacarbazine; Disease

2011
Phase I study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2012, Feb-15, Volume: 18, Issue:4

    Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Female; Humans; Male

2012
Randomized phase II trial of sorafenib with temsirolimus or tipifarnib in untreated metastatic melanoma (S0438).
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2012, Feb-15, Volume: 18, Issue:4

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; F

2012
A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity.
    Annals of surgical oncology, 2012, Volume: 19, Issue:12

    Topics: Antineoplastic Combined Chemotherapy Protocols; Extremities; Female; Follow-Up Studies; Humans; Male

2012
Sorafenib in advanced melanoma: a critical role for pharmacokinetics?
    British journal of cancer, 2012, Jul-24, Volume: 107, Issue:3

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Benzenesulfonates; Disease-Free Survival; Fem

2012
Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.
    PloS one, 2012, Volume: 7, Issue:11

    Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Pharmacological; Carboplatin; Dise

2012
Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013, Jan-20, Volume: 31, Issue:3

    Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Double-Blind Met

2013
Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis.
    British journal of cancer, 2006, Sep-04, Volume: 95, Issue:5

    Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Benzenesulfonates; DNA Primers; Female; Gen

2006
Phase I trial of sorafenib in combination with IFN alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2007, Mar-15, Volume: 13, Issue:6

    Topics: Adult; Aged; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Biomarke

2007
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.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008, May-01, Volume: 26, Issue:13

    Topics: Administration, Oral; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy

2008

Other Studies

81 other studies available for niacinamide and Melanoma

ArticleYear
Cutaneous immune-related adverse events and photodamaged skin in patients with metastatic melanoma: could nicotinamide be useful?
    Clinical and experimental dermatology, 2022, Volume: 47, Issue:8

    Topics: Humans; Immunotherapy; Melanoma; Neoplasms, Second Primary; Niacinamide; Retrospective Studies; Skin

2022
The SRPK inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl) isonicotinamide (SRPIN340) increases the immune response against metastatic melanoma in mice.
    Biochemical pharmacology, 2022, Volume: 203

    Topics: Animals; Humans; Immunity; Melanoma; Mice; Niacinamide; Piperidines; Protein Serine-Threonine Kinase

2022
KDOAM-25 Overcomes Resistance to MEK Inhibitors by Targeting KDM5B in Uveal Melanoma.
    BioMed research international, 2022, Volume: 2022

    Topics: Annexins; Cell Line, Tumor; Cell Proliferation; Epigenesis, Genetic; Glycine; Histones; Humans; Jumo

2022
Nicotinamide for skin cancer chemoprevention: effects of nicotinamide on melanoma in vitro and in vivo.
    Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology, 2020, Feb-19, Volume: 19, Issue:2

    Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Movement; Cell Surviv

2020
Identification of the Nicotinamide Salvage Pathway as a New Toxification Route for Antimetabolites.
    Cell chemical biology, 2018, 04-19, Volume: 25, Issue:4

    Topics: Animals; Antimetabolites, Antineoplastic; Cell Line, Tumor; Cell Survival; Glycolysis; Humans; Melan

2018
Nicotinamide inhibits vasculogenic mimicry, an alternative vascularization pathway observed in highly aggressive melanoma.
    PloS one, 2013, Volume: 8, Issue:2

    Topics: Blood Vessels; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Gene Expression Profiling; Humans;

2013
Innovations in the treatment of melanoma.
    Journal of the National Comprehensive Cancer Network : JNCCN, 2004, Volume: 2 Suppl 3

    Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Cancer Vaccines; DNA, Antisense; Genetic Therapy; Hu

2004
Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013, Jul-01, Volume: 31, Issue:19

    Topics: Aged; Antineoplastic Agents; Arginine; Back; Cell Survival; Enzyme Activation; Extracellular Signal-

2013
Recurrent BRAF kinase fusions in melanocytic tumors offer an opportunity for targeted therapy.
    Pigment cell & melanoma research, 2013, Volume: 26, Issue:6

    Topics: Adolescent; Adult; Child, Preschool; Enzyme Activation; Female; Gene Rearrangement; Humans; Indoles;

2013
Overman rearrangement and Pomeranz-Fritsch reaction for the synthesis of benzoazepinoisoquinolones to discover novel antitumor agents.
    European journal of medicinal chemistry, 2013, Volume: 70

    Topics: Antineoplastic Agents; Benzazepines; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationshi

2013
SIRT1 regulates lamellipodium extension and migration of melanoma cells.
    The Journal of investigative dermatology, 2014, Volume: 134, Issue:6

    Topics: Animals; Cell Movement; Female; Gene Expression Regulation, Neoplastic; Melanoma; Melanoma, Experime

2014
Response of patients with metastatic uveal melanoma to combined treatment with fotemustine and sorafenib.
    Acta ophthalmologica, 2014, Volume: 92, Issue:8

    Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Liver Neoplasms; Lymphatic Met

2014
Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.
    Experimental dermatology, 2014, Volume: 23, Issue:7

    Topics: Cell Line, Tumor; Cell Survival; Cells, Cultured; DNA Damage; DNA Repair; Humans; Melanocytes; Melan

2014
Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma.
    British journal of cancer, 2014, Jul-29, Volume: 111, Issue:3

    Topics: Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Gene Knockdown Techniques; Humans; Melanoma; Mic

2014
Molecular ultrasound imaging using contrast agents targeting endoglin, vascular endothelial growth factor receptor 2 and integrin.
    Ultrasound in medicine & biology, 2015, Volume: 41, Issue:1

    Topics: Animals; Biomarkers, Tumor; Cell Line, Tumor; Contrast Media; Endoglin; Female; Integrin alphaV; Int

2015
Synthesis and evaluation of ¹²³/¹³¹I-Iochlonicotinamide as a novel SPECT probe for malignant melanoma.
    Bioorganic & medicinal chemistry, 2015, May-01, Volume: 23, Issue:9

    Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Iodine

2015
Multifunctional bioscaffolds for 3D culture of melanoma cells reveal increased MMP activity and migration with BRAF kinase inhibition.
    Proceedings of the National Academy of Sciences of the United States of America, 2015, Apr-28, Volume: 112, Issue:17

    Topics: Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Collagenases; Humans; Hydrogels; Indoles;

2015
Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts.
    Journal of translational medicine, 2015, Jun-13, Volume: 13

    Topics: Animals; Antibodies, Neoplasm; Cell Line, Tumor; Cell Proliferation; Cellular Apoptosis Susceptibili

2015
Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.
    Oncotarget, 2015, Sep-29, Volume: 6, Issue:29

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Blotting, Western; Caspase 3; Ce

2015
Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma.
    Oncotarget, 2016, Jan-12, Volume: 7, Issue:2

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Blotting, Western; Cadherins; Cell Line, Tu

2016
A case series of anal melanoma including the results of treatment with imatinib in selected patients.
    Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, 2016, Volume: 18, Issue:9

    Topics: Adult; Aged; Aged, 80 and over; Anal Canal; Antineoplastic Agents; Anus Neoplasms; Dacarbazine; Dige

2016
B-Raf Inhibition in the Clinic: Present and Future.
    Annual review of medicine, 2016, Volume: 67

    Topics: Antineoplastic Agents; Colonic Neoplasms; Drug Resistance, Neoplasm; Humans; Imidazoles; Indoles; MA

2016
Inhibition of Cell Proliferation in an NRAS Mutant Melanoma Cell Line by Combining Sorafenib and α-Mangostin.
    PloS one, 2016, Volume: 11, Issue:5

    Topics: Cell Line, Tumor; Cell Proliferation; Genes, ras; Humans; Melanoma; Niacinamide; Phenylurea Compound

2016
Combining nanoliposomal ceramide with sorafenib synergistically inhibits melanoma and breast cancer cell survival to decrease tumor development.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2008, Jun-01, Volume: 14, Issue:11

    Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates; Blotting, Western; Bre

2008
Effectively targeting BRAF in melanoma: a formidable challenge.
    Pigment cell & melanoma research, 2008, Volume: 21, Issue:4

    Topics: Antineoplastic Agents; Benzenesulfonates; Clinical Trials as Topic; Drug Delivery Systems; Drug Eval

2008
Secondary erythrocytosis produced by the tyrosine kinase inhibitors sunitinib and sorafenib.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008, Aug-20, Volume: 26, Issue:24

    Topics: Aged, 80 and over; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Carcinoma, R

2008
Searching for the Achilles' heel of melanoma cells: new treatment modalities.
    Pigment cell & melanoma research, 2008, Volume: 21, Issue:5

    Topics: Animals; Antineoplastic Agents; Apoptosis; Benzenesulfonates; Clinical Trials as Topic; Enzyme Inhib

2008
Follicular hyperplasia on the face subsequent to therapy with sorafenib. A new skin side effect.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2009, Volume: 23, Issue:8

    Topics: Aged, 80 and over; Antineoplastic Agents; Benzenesulfonates; Humans; Hyperplasia; Lung Neoplasms; Ma

2009
CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations.
    Oncogene, 2009, Jan-08, Volume: 28, Issue:1

    Topics: Apoptosis; Benzenesulfonates; Cell Line, Tumor; Drug Resistance, Neoplasm; Gene Knockdown Techniques

2009
Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines.
    Journal of translational medicine, 2008, Sep-29, Volume: 6

    Topics: Antineoplastic Agents; Apoptosis; Benzenesulfonates; Blotting, Western; Cell Cycle; Cell Line, Tumor

2008
Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib.
    Nature clinical practice. Oncology, 2008, Volume: 5, Issue:12

    Topics: Aged; Antineoplastic Agents; Anus Neoplasms; Benzenesulfonates; Dacarbazine; Humans; Male; Melanoma;

2008
Targeting metastatic melanoma.
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2008, Dec-15, Volume: 65, Issue:24 Suppl 9

    Topics: Antibodies, Monoclonal; Antigens, CD; Antineoplastic Agents; Benzenesulfonates; Cancer Vaccines; Cli

2008
Molecular determinants of melanoma malignancy: selecting targets for improved efficacy of chemotherapy.
    Molecular cancer therapeutics, 2009, Volume: 8, Issue:3

    Topics: Animals; Antineoplastic Agents; Benzenesulfonates; Biomarkers, Tumor; Dacarbazine; Drug Delivery Sys

2009
Multiple colon ulcerations, perforation and death during treatment of malignant melanoma with sorafenib.
    Deutsche medizinische Wochenschrift (1946), 2009, Volume: 134, Issue:28-29

    Topics: Abdomen, Acute; Aged; Antineoplastic Agents; Benzenesulfonates; Colectomy; Colonic Diseases; Diarrhe

2009
Development of a novel chemical class of BRAF inhibitors offers new hope for melanoma treatment.
    Future oncology (London, England), 2009, Volume: 5, Issue:6

    Topics: Animals; Antineoplastic Agents; Benzamides; Benzenesulfonates; Cell Line, Tumor; Humans; Imatinib Me

2009
Discovery of [18F]N-(2-(diethylamino)ethyl)-6-fluoronicotinamide: a melanoma positron emission tomography imaging radiotracer with high tumor to body contrast ratio and rapid renal clearance.
    Journal of medicinal chemistry, 2009, Sep-10, Volume: 52, Issue:17

    Topics: Animals; Drug Discovery; Humans; Kidney; Melanoma; Metabolic Clearance Rate; Mice; Niacinamide; Posi

2009
Rapid response to therapy of neurocutaneous melanosis with leptomeningeal melanoma.
    Pediatric blood & cancer, 2010, Volume: 54, Issue:1

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Child, Preschool; Cyclophosphamid

2010
C-Raf is associated with disease progression and cell proliferation in a subset of melanomas.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2009, Sep-15, Volume: 15, Issue:18

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzenesulfonates; Cell Line, Tumor; Cell Proliferation;

2009
The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells.
    International journal of cancer, 2010, Apr-01, Volume: 126, Issue:7

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates; Blotting, Wes

2010
Synthesis and antiproliferative activity of pyrrolo[3,2-b]pyridine derivatives against melanoma.
    Bioorganic & medicinal chemistry letters, 2010, Jan-01, Volume: 20, Issue:1

    Topics: Antineoplastic Agents; Benzenesulfonates; Cell Line; Humans; Melanoma; Niacinamide; Phenylurea Compo

2010
C-Raf inhibits MAPK activation and transformation by B-Raf(V600E).
    Molecular cell, 2009, Nov-13, Volume: 36, Issue:3

    Topics: Animals; Benzenesulfonates; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell

2009
Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines.
    Bioorganic & medicinal chemistry letters, 2010, Mar-01, Volume: 20, Issue:5

    Topics: Antineoplastic Agents; Benzenesulfonates; Binding Sites; Cell Line, Tumor; Crystallography, X-Ray; D

2010
High-contrast PET of melanoma using (18)F-MEL050, a selective probe for melanin with predominantly renal clearance.
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2010, Volume: 51, Issue:3

    Topics: Animals; Autoradiography; Cell Line, Tumor; Cell Transformation, Neoplastic; Contrast Media; Female;

2010
Optimal de novo design of MRM experiments for rapid assay development in targeted proteomics.
    Journal of proteome research, 2010, May-07, Volume: 9, Issue:5

    Topics: Algorithms; Animals; Artificial Intelligence; Benzenesulfonates; Cell Line, Tumor; Chromatography, H

2010
Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT.
    British journal of cancer, 2010, Apr-13, Volume: 102, Issue:8

    Topics: Adult; Aged; Antineoplastic Agents; Benzamides; Benzenesulfonates; Female; Humans; Imatinib Mesylate

2010
Sorafenib, a multikinase inhibitor, enhances the response of melanoma to regional chemotherapy.
    Molecular cancer therapeutics, 2010, Volume: 9, Issue:7

    Topics: Animals; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Apoptosi

2010
A structure-based approach for mapping adverse drug reactions to the perturbation of underlying biological pathways.
    PloS one, 2010, Aug-23, Volume: 5, Issue:8

    Topics: Breast Neoplasms; Computational Biology; Databases, Factual; Diabetes Mellitus, Type 2; Drug-Related

2010
The farnesyl transferase inhibitor lonafarnib inhibits mTOR signaling and enforces sorafenib-induced apoptosis in melanoma cells.
    The Journal of investigative dermatology, 2011, Volume: 131, Issue:2

    Topics: Antineoplastic Agents; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Benzenesulfonates; C

2011
Oncogenic RAF: a brief history of time.
    Pigment cell & melanoma research, 2010, Volume: 23, Issue:6

    Topics: Benzenesulfonates; Drug Screening Assays, Antitumor; Enzyme Activation; Extracellular Signal-Regulat

2010
Improved detection of regional melanoma metastasis using 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide, a melanin-specific PET probe, by perilesional administration.
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2011, Volume: 52, Issue:1

    Topics: Animals; Fluorine Radioisotopes; Lymphatic Metastasis; Melanins; Melanoma; Mice; Mice, Inbred C57BL;

2011
Regional squamous cell carcinomas following systemic sorafenib therapy and isolated limb infusion for regionally advanced metastatic melanoma of the limb.
    Archives of dermatology, 2010, Volume: 146, Issue:12

    Topics: Aged; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Squamous Cell; Drug Administration Routes

2010
Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2011, May-15, Volume: 17, Issue:10

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Autophagy; Benzenesulfonates; Cell Count; C

2011
B-Raf associates with and activates the NHE1 isoform of the Na+/H+ exchanger.
    The Journal of biological chemistry, 2011, Apr-15, Volume: 286, Issue:15

    Topics: Amino Acid Substitution; Animals; Benzenesulfonates; Cation Transport Proteins; Cell Movement; Cell

2011
Structure based design and syntheses of amino-1H-pyrazole amide derivatives as selective Raf kinase inhibitors in melanoma cells.
    Bioorganic & medicinal chemistry, 2011, Mar-15, Volume: 19, Issue:6

    Topics: Amides; Antineoplastic Agents; Benzenesulfonates; Binding Sites; Cell Line, Tumor; Computer Simulati

2011
Sequential therapy with JX-594, a targeted oncolytic poxvirus, followed by sorafenib in hepatocellular carcinoma: preclinical and clinical demonstration of combination efficacy.
    Molecular therapy : the journal of the American Society of Gene Therapy, 2011, Volume: 19, Issue:6

    Topics: Animals; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Cell Line, Tumor; Fema

2011
Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines.
    European journal of medicinal chemistry, 2011, Volume: 46, Issue:8

    Topics: Animals; Antineoplastic Agents; Benzenesulfonates; Cell Line, Tumor; Cell Proliferation; Drug Screen

2011
Constitutive ERK activity induces downregulation of tristetraprolin, a major protein controlling interleukin8/CXCL8 mRNA stability in melanoma cells.
    American journal of physiology. Cell physiology, 2011, Volume: 301, Issue:3

    Topics: Animals; Antibodies; Antineoplastic Agents; Apoptosis; Autophagy; Benzamides; Benzenesulfonates; Cel

2011
[News on melanoma from the 2010 Dermatology Days in Paris].
    Annales de dermatologie et de venereologie, 2011, Volume: 138, Issue:5 Suppl 1

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Biomarkers, Tumor; Chemotherapy,

2011
Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition.
    The Journal of investigative dermatology, 2011, Volume: 131, Issue:10

    Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates;

2011
Setting up a kinase discovery and development project.
    Current topics in microbiology and immunology, 2012, Volume: 355

    Topics: Adenosine Triphosphate; Animals; Crystallography, X-Ray; Drug Discovery; Drug Evaluation, Preclinica

2012
Glutamatergic pathway targeting in melanoma: single-agent and combinatorial therapies.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2011, Nov-15, Volume: 17, Issue:22

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Cell Cycle; Cell Line, T

2011
Differential modulatory effects of GSK-3β and HDM2 on sorafenib-induced AIF nuclear translocation (programmed necrosis) in melanoma.
    Molecular cancer, 2011, Sep-19, Volume: 10

    Topics: Animals; Antineoplastic Agents; Apoptosis; Apoptosis Inducing Factor; Apoptosis Regulatory Proteins;

2011
Design, synthesis, and antiproliferative activity of 3,4-diarylpyrazole-1-carboxamide derivatives against melanoma cell line.
    Archiv der Pharmazie, 2011, Volume: 344, Issue:11

    Topics: Antineoplastic Agents; Benzenesulfonates; Cell Line, Tumor; Cell Proliferation; Drug Screening Assay

2011
Fluvastatin enhances sorafenib cytotoxicity in melanoma cells via modulation of AKT and JNK signaling pathways.
    Anticancer research, 2011, Volume: 31, Issue:10

    Topics: Anthracenes; Benzenesulfonates; Cell Death; Cell Line, Tumor; Cell Proliferation; Chromones; Drug Sc

2011
New imidazo[2,1-b]thiazole derivatives: synthesis, in vitro anticancer evaluation, and in silico studies.
    European journal of medicinal chemistry, 2011, Volume: 46, Issue:12

    Topics: Antineoplastic Agents; Benzenesulfonates; Cell Line, Tumor; Cell Proliferation; Drug Screening Assay

2011
Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?
    Experimental dermatology, 2011, Volume: 20, Issue:12

    Topics: Adolescent; Antineoplastic Agents; Benzenesulfonates; Butadienes; Cell Survival; Dacarbazine; Drug T

2011
Chemosensitivity of conjunctival melanoma cell lines to target-specific chemotherapeutic agents.
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2013, Volume: 251, Issue:1

    Topics: Antineoplastic Agents; Benzophenones; Boronic Acids; Bortezomib; Cell Proliferation; Conjunctival Ne

2013
Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma.
    Molecular cancer therapeutics, 2012, Volume: 11, Issue:11

    Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Death; Cell Line, Tumor;

2012
INHIBITION OF TUMOR CELL GLYCOLYSIS BY DPNH2, AND REVERSAL OF THE INHIBITION BY DPN, PYRUVATE OR METHYLENE BLUE.
    Zeitschrift fur Naturforschung. Teil B, Chemie, Biochemie, Biophysik, Biologie und verwandte Gebiete, 1963, Volume: 18

    Topics: Animals; Carbohydrate Metabolism; Carcinoma, Ehrlich Tumor; Carcinoma, Krebs 2; Glycolysis; Melanoma

1963
B-RAF is a therapeutic target in melanoma.
    Oncogene, 2004, Aug-19, Volume: 23, Issue:37

    Topics: Benzenesulfonates; Cell Line, Tumor; Humans; Melanoma; Niacinamide; Phenylurea Compounds; Proto-Onco

2004
Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors.
    Cancer research, 2005, Mar-15, Volume: 65, Issue:6

    Topics: Animals; Apoptosis; Benzenesulfonates; Cell Growth Processes; Cell Line, Tumor; Humans; MAP Kinase S

2005
The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells.
    Cancer research, 2006, Feb-01, Volume: 66, Issue:3

    Topics: Apoptosis; Apoptosis Regulatory Proteins; bcl-Associated Death Protein; Benzenesulfonates; Caspases;

2006
Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006).
    The American journal of pathology, 2006, Volume: 169, Issue:5

    Topics: Animals; Antineoplastic Agents; Apoptosis; Benzenesulfonates; Carcinoma, Renal Cell; Cell Proliferat

2006
Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment.
    The British journal of dermatology, 2007, Volume: 156, Issue:6

    Topics: Androstadienes; Apoptosis; Benzenesulfonates; Blotting, Western; Cell Line, Tumor; Cell Proliferatio

2007
Mutant V600E BRAF increases hypoxia inducible factor-1alpha expression in melanoma.
    Cancer research, 2007, Apr-01, Volume: 67, Issue:7

    Topics: Benzenesulfonates; Cell Hypoxia; Cell Line, Tumor; Cell Survival; Gene Expression Profiling; Gene Ex

2007
Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma.
    Journal of translational medicine, 2007, Jul-18, Volume: 5

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Cell Movement; Cell Prol

2007
GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines.
    The Journal of biological chemistry, 2008, Jan-11, Volume: 283, Issue:2

    Topics: Apoptosis; Benzenesulfonates; Cell Adhesion; Cell Death; Cell Line, Tumor; Glycogen Synthase Kinase

2008
Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells.
    The Journal of investigative dermatology, 2008, Volume: 128, Issue:8

    Topics: Androstadienes; Apoptosis; Benzenesulfonates; Butadienes; Cell Line, Tumor; Cell Proliferation; Chro

2008
Dramatic reduction of chronic lymphoedema of the lower limb with sorafenib therapy.
    Melanoma research, 2008, Volume: 18, Issue:2

    Topics: Adult; Antineoplastic Agents; Benzenesulfonates; Female; Humans; Lower Extremity; Lymphatic Metastas

2008
Differential effects of NAD, nicotinamide and related compounds upon growth and nucleoside incorporation in human cells.
    Biochemical pharmacology, 1983, Mar-01, Volume: 32, Issue:5

    Topics: Adenosine; Cell Division; Cell Line; DNA Repair; DNA, Neoplasm; Fibroblasts; Humans; Melanoma; NAD;

1983
Transient perfusion and radiosensitizing effect after nicotinamide, carbogen, and perflubron emulsion administration.
    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 1996, Volume: 39, Issue:3

    Topics: Adenocarcinoma; Animals; Carbon Dioxide; Emulsions; Female; Fluorocarbons; Humans; Hydrocarbons, Bro

1996