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)
| Excerpt | Relevance | Reference |
|---|---|---|
| "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." | 9.22 | Sorafenib 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." | 9.22 | Copy 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)." | 9.20 | A 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." | 9.19 | Correlation 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)." | 9.19 | A 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)." | 9.17 | Cutaneous 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." | 9.17 | Phase 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." | 9.16 | Phase 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)." | 9.16 | Sorafenib 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." | 9.16 | A 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." | 9.16 | Phase 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." | 9.15 | Sorafenib 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." | 9.15 | Interaction 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." | 9.15 | Sorafenib 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." | 9.14 | A 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." | 9.14 | Expression 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." | 9.13 | 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. ( 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)." | 9.12 | Sorafenib 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." | 9.12 | Phase 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." | 8.88 | Sorafenib 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." | 7.81 | Early 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." | 7.77 | Differential 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." | 7.75 | Multiple 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." | 7.74 | Preclinical 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." | 7.74 | GSK-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." | 6.79 | Regulation 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." | 6.79 | 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. ( 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." | 6.44 | Metastatic 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." | 5.43 | Inhibition 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." | 5.43 | Fisetin, 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." | 5.42 | Fisetin, 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." | 5.37 | Fluvastatin 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." | 5.36 | The 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." | 5.22 | Sorafenib 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." | 5.22 | Copy 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)." | 5.20 | A 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." | 5.19 | Correlation 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)." | 5.19 | A 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)." | 5.17 | Cutaneous 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." | 5.17 | Phase 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." | 5.16 | A 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." | 5.16 | Phase 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)." | 5.16 | Sorafenib 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." | 5.16 | Phase 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." | 5.15 | Interaction 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." | 5.15 | Sorafenib 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." | 5.15 | Sorafenib 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." | 5.14 | Expression 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." | 5.14 | A 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." | 5.13 | 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. ( 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)." | 5.12 | Sorafenib 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." | 5.12 | Phase 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." | 4.88 | Sorafenib 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." | 3.81 | Early 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." | 3.79 | Chemosensitivity 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." | 3.77 | Measurements 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." | 3.77 | Glutamatergic 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." | 3.77 | B-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." | 3.77 | Differential 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." | 3.75 | Multiple 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." | 3.74 | Preclinical 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." | 3.74 | Combined 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." | 3.74 | Combination 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." | 3.74 | GSK-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." | 3.66 | Differential 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." | 2.90 | Correlation 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)." | 2.87 | Pimasertib-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." | 2.79 | Regulation 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." | 2.79 | 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. ( 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." | 2.75 | Safety, 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." | 2.52 | Ocular 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." | 2.44 | Metastatic 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." | 2.44 | Sorafenib: 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." | 2.43 | Sorafenib. ( 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." | 1.72 | Cutaneous 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." | 1.43 | Inhibition 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." | 1.43 | B-Raf Inhibition in the Clinic: Present and Future. ( Fiskus, W; Mitsiades, N, 2016) |
| "Anal melanoma is a rare malignancy with a poor prognosis." | 1.43 | A 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." | 1.43 | Fisetin, 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." | 1.42 | Fisetin, 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." | 1.42 | Synthesis 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." | 1.40 | Targeting 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." | 1.40 | Nicotinamide 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." | 1.40 | SIRT1 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." | 1.38 | Synthetic 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." | 1.37 | Fluvastatin 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." | 1.37 | Fibroblast 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." | 1.36 | The 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." | 1.35 | Development 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." | 1.35 | Combined 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) |
| Timeframe | Studies, this research(%) | All Research% |
|---|---|---|
| pre-1990 | 2 (1.64) | 18.7374 |
| 1990's | 1 (0.82) | 18.2507 |
| 2000's | 36 (29.51) | 29.6817 |
| 2010's | 78 (63.93) | 24.3611 |
| 2020's | 5 (4.10) | 2.80 |
| Authors | Studies |
|---|---|
| De Giorgi, V | 1 |
| Colombo, J | 1 |
| Trane, L | 1 |
| Silvestri, F | 1 |
| Venturi, F | 1 |
| Zuccaro, B | 1 |
| Doni, L | 1 |
| Stanganelli, I | 1 |
| Covarelli, P | 1 |
| Moreira, GA | 1 |
| Caetano, MMM | 1 |
| do Vale, JA | 1 |
| de Paiva, JC | 1 |
| Gonçalves, VHS | 1 |
| Almeida, AA | 1 |
| Silva, LVG | 1 |
| Martim, FRG | 1 |
| de Andrade Barros, MV | 1 |
| Guimarães, GR | 1 |
| de Oliveira Santos, L | 1 |
| de Souza, APM | 1 |
| Machado-Neves, M | 1 |
| Teixeira, RR | 1 |
| Silva-Júnior, A | 1 |
| Fietto, JLR | 1 |
| Boroni, M | 1 |
| de Oliveira, LL | 1 |
| Bressan, GC | 1 |
| Zhang, H | 2 |
| Liu, X | 1 |
| Chen, Y | 1 |
| Xu, R | 1 |
| He, S | 1 |
| Malesu, R | 1 |
| Martin, AJ | 1 |
| Lyons, JG | 1 |
| Scolyer, RA | 1 |
| Chen, AC | 1 |
| McKenzie, CA | 1 |
| Madore, J | 1 |
| Halliday, GM | 3 |
| Damian, DL | 4 |
| Lebbé, C | 2 |
| Italiano, A | 1 |
| Houédé, N | 1 |
| Awada, A | 1 |
| Aftimos, P | 1 |
| Lesimple, T | 2 |
| Dinulescu, M | 1 |
| Schellens, JHM | 1 |
| Leijen, S | 1 |
| Rottey, S | 1 |
| Kruse, V | 1 |
| Kefford, R | 2 |
| Raymond, E | 1 |
| Faivre, S | 1 |
| Pages, C | 1 |
| Gomez-Roca, C | 1 |
| Schueler, A | 1 |
| Goodstal, S | 1 |
| Massimini, G | 1 |
| Delord, JP | 1 |
| Lim, SY | 1 |
| Menzies, AM | 1 |
| Rizos, H | 1 |
| Minocha, R | 1 |
| Liu, T | 1 |
| Yang, H | 1 |
| Mou, Y | 1 |
| van Dijk, EHC | 1 |
| Kruit, WHJ | 1 |
| Jager, MJ | 1 |
| Luyten, GPM | 1 |
| Vingerling, JR | 1 |
| Boon, CJF | 1 |
| Buonvicino, D | 1 |
| Mazzola, F | 1 |
| Zamporlini, F | 1 |
| Resta, F | 1 |
| Ranieri, G | 1 |
| Camaioni, E | 1 |
| Muzzi, M | 1 |
| Zecchi, R | 1 |
| Pieraccini, G | 1 |
| Dölle, C | 1 |
| Calamante, M | 1 |
| Bartolucci, G | 1 |
| Ziegler, M | 1 |
| Stecca, B | 1 |
| Raffaelli, N | 1 |
| Chiarugi, A | 1 |
| Itzhaki, O | 1 |
| Greenberg, E | 1 |
| Shalmon, B | 1 |
| Kubi, A | 1 |
| Treves, AJ | 1 |
| Shapira-Frommer, R | 1 |
| Avivi, C | 1 |
| Ortenberg, R | 1 |
| Ben-Ami, E | 1 |
| Schachter, J | 1 |
| Besser, MJ | 1 |
| Markel, G | 1 |
| Pavlick, AC | 2 |
| Bahadoran, P | 3 |
| Allegra, M | 3 |
| Le Duff, F | 1 |
| Long-Mira, E | 1 |
| Hofman, P | 1 |
| Giacchero, D | 2 |
| Passeron, T | 2 |
| Lacour, JP | 2 |
| Ballotti, R | 3 |
| Degen, A | 3 |
| Weichenthal, M | 2 |
| Ugurel, S | 2 |
| Trefzer, U | 2 |
| Kilian, K | 1 |
| Garbe, C | 5 |
| Egberts, F | 3 |
| Poppe, LM | 1 |
| Hauschild, A | 5 |
| Gutzmer, R | 3 |
| Botton, T | 1 |
| Yeh, I | 1 |
| Nelson, T | 1 |
| Vemula, SS | 1 |
| Sparatta, A | 1 |
| Garrido, MC | 1 |
| Rocchi, S | 1 |
| McCalmont, TH | 1 |
| LeBoit, PE | 1 |
| Burton, EA | 1 |
| Bollag, G | 2 |
| Bastian, BC | 1 |
| Romero, AI | 1 |
| Chaput, N | 1 |
| Poirier-Colame, V | 1 |
| Rusakiewicz, S | 1 |
| Jacquelot, N | 1 |
| Chaba, K | 1 |
| Mortier, E | 1 |
| Jacques, Y | 1 |
| Caillat-Zucman, S | 1 |
| Flament, C | 1 |
| Caignard, A | 1 |
| Messaoudene, M | 1 |
| Aupérin, A | 1 |
| Vielh, P | 1 |
| Dessen, P | 1 |
| Porta, C | 1 |
| Mateus, C | 1 |
| Ayyoub, M | 1 |
| Valmori, D | 1 |
| Eggermont, A | 1 |
| Robert, C | 3 |
| Zitvogel, L | 1 |
| Li, B | 1 |
| Wang, G | 1 |
| Yang, M | 1 |
| Xu, Z | 1 |
| Zeng, B | 1 |
| Wang, H | 1 |
| Shen, J | 1 |
| Chen, K | 1 |
| Zhu, W | 1 |
| Kunimoto, R | 1 |
| Jimbow, K | 1 |
| Tanimura, A | 1 |
| Sato, M | 1 |
| Horimoto, K | 1 |
| Hayashi, T | 1 |
| Hisahara, S | 1 |
| Sugino, T | 1 |
| Hirobe, T | 1 |
| Yamashita, T | 1 |
| Horio, Y | 1 |
| Monk, P | 1 |
| Lam, E | 1 |
| Mortazavi, A | 1 |
| Kendra, K | 1 |
| Lesinski, GB | 1 |
| Mace, TA | 1 |
| Geyer, S | 1 |
| Carson, WE | 1 |
| Tahiri, S | 1 |
| Bhinder, A | 1 |
| Clinton, SK | 1 |
| Olencki, T | 1 |
| Holderfield, M | 1 |
| Nagel, TE | 1 |
| Stuart, DD | 1 |
| Wilson, MA | 2 |
| Zhao, F | 3 |
| Letrero, R | 2 |
| D'Andrea, K | 2 |
| Rimm, DL | 4 |
| Kirkwood, JM | 4 |
| Kluger, HM | 4 |
| Lee, SJ | 4 |
| Schuchter, LM | 5 |
| Flaherty, KT | 11 |
| Nathanson, KL | 6 |
| Niederkorn, A | 1 |
| Wackernagel, W | 1 |
| Artl, M | 1 |
| Schwantzer, G | 1 |
| Aigner, B | 1 |
| Richtig, E | 1 |
| Thompson, BC | 1 |
| Surjana, D | 1 |
| Mahalingam, D | 1 |
| Malik, L | 1 |
| Beeram, M | 2 |
| Rodon, J | 1 |
| Sankhala, K | 1 |
| Mita, A | 1 |
| Benjamin, D | 1 |
| Ketchum, N | 1 |
| Michalek, J | 1 |
| Tolcher, A | 1 |
| Wright, J | 1 |
| Sarantopoulos, J | 1 |
| Gammons, MV | 1 |
| Lucas, R | 1 |
| Dean, R | 1 |
| Coupland, SE | 1 |
| Oltean, S | 1 |
| Bates, DO | 1 |
| Leguerney, I | 1 |
| Scoazec, JY | 1 |
| Gadot, N | 1 |
| Robin, N | 1 |
| Pénault-Llorca, F | 1 |
| Victorin, S | 1 |
| Lassau, N | 2 |
| Chang, CC | 1 |
| Chang, CH | 1 |
| Shen, CC | 1 |
| Chen, CL | 1 |
| Liu, RS | 1 |
| Lin, MH | 1 |
| Wang, HE | 1 |
| Leight, JL | 1 |
| Tokuda, EY | 1 |
| Jones, CE | 1 |
| Lin, AJ | 1 |
| Anseth, KS | 1 |
| Sullivan, RJ | 1 |
| Ibrahim, N | 1 |
| Lawrence, DP | 1 |
| Aldridge, J | 1 |
| Giobbie-Hurder, A | 1 |
| Hodi, FS | 2 |
| Conley, C | 1 |
| Mier, JW | 4 |
| Atkins, MB | 4 |
| McDermott, DF | 2 |
| Lee, WR | 1 |
| Shen, SC | 1 |
| Shih, YH | 1 |
| Chou, CL | 1 |
| Tseng, JT | 1 |
| Chin, SY | 1 |
| Liu, KH | 1 |
| Chen, YC | 1 |
| Jiang, MC | 1 |
| Niro, A | 1 |
| Strippoli, S | 1 |
| Alessio, G | 1 |
| Sborgia, L | 1 |
| Recchimurzo, N | 1 |
| Guida, M | 1 |
| Pal, HC | 2 |
| Baxter, RD | 1 |
| Hunt, KM | 1 |
| Agarwal, J | 1 |
| Elmets, CA | 2 |
| Athar, M | 2 |
| Afaq, F | 2 |
| Khare, S | 1 |
| Roszik, J | 1 |
| Woodman, SE | 2 |
| Wubbenhorst, B | 1 |
| Diamond, AC | 1 |
| Strickland, LR | 1 |
| Kappes, JC | 1 |
| Katiyar, SK | 1 |
| Knowles, J | 1 |
| Lynch, AC | 1 |
| Warrier, SK | 1 |
| Henderson, M | 1 |
| Heriot, AG | 1 |
| Fiskus, W | 1 |
| Mitsiades, N | 1 |
| Okano, S | 1 |
| Xia, Y | 1 |
| Li, Y | 1 |
| Westover, KD | 1 |
| Sun, J | 1 |
| Chen, H | 1 |
| Zhang, J | 1 |
| Fisher, DE | 1 |
| Mouriaux, F | 1 |
| Servois, V | 1 |
| Parienti, JJ | 1 |
| Thyss, A | 2 |
| Dutriaux, C | 1 |
| Neidhart-Berard, EM | 1 |
| Penel, N | 1 |
| Delcambre, C | 1 |
| Peyro Saint Paul, L | 1 |
| Pham, AD | 1 |
| Heutte, N | 1 |
| Piperno-Neumann, S | 1 |
| Joly, F | 1 |
| Tran, MA | 1 |
| Smith, CD | 2 |
| Kester, M | 1 |
| Robertson, GP | 2 |
| Kahler, KC | 1 |
| Livingstone, E | 2 |
| Fecher, LA | 1 |
| Amaravadi, R | 1 |
| Alexandrescu, DT | 1 |
| McClure, R | 1 |
| Farzanmehr, H | 1 |
| Dasanu, CA | 1 |
| Melnikova, VO | 1 |
| Bar-Eli, M | 1 |
| Lopez, V | 1 |
| Pinazo, I | 1 |
| Marti, N | 1 |
| Monteagudo, C | 1 |
| Jorda, E | 1 |
| Smalley, KS | 2 |
| Xiao, M | 1 |
| Villanueva, J | 1 |
| Nguyen, TK | 1 |
| Van Belle, P | 1 |
| Elder, DE | 1 |
| Wang, Y | 1 |
| Herlyn, M | 3 |
| Eustace, AJ | 1 |
| Crown, J | 1 |
| Clynes, M | 1 |
| O'Donovan, N | 1 |
| Quintás-Cardama, A | 1 |
| Lazar, AJ | 2 |
| Kim, K | 1 |
| Ross, M | 1 |
| Hwu, P | 2 |
| Poust, J | 1 |
| Jilaveanu, L | 1 |
| Zito, C | 1 |
| Camp, RL | 2 |
| Yang, J | 1 |
| Zaja-Milatovic, S | 1 |
| Thu, YM | 1 |
| Lee, F | 1 |
| Smykla, R | 1 |
| Richmond, A | 1 |
| Dhomen, N | 1 |
| Marais, R | 4 |
| Frieling, T | 1 |
| Heise, J | 1 |
| Wassilew, SW | 1 |
| Greguric, I | 3 |
| Taylor, SR | 2 |
| Denoyer, D | 3 |
| Ballantyne, P | 1 |
| Berghofer, P | 1 |
| Roselt, P | 3 |
| Pham, TQ | 1 |
| Mattner, F | 1 |
| Bourdier, T | 1 |
| Neels, OC | 3 |
| Dorow, DS | 3 |
| Loc'h, C | 1 |
| Hicks, RJ | 3 |
| Katsifis, A | 3 |
| Subbiah, V | 1 |
| Wolff, JE | 1 |
| Jilaveanu, LB | 1 |
| Zito, CR | 1 |
| Aziz, SA | 1 |
| Conrad, PJ | 1 |
| Schmitz, JC | 1 |
| Sznol, M | 1 |
| López-Fauqued, M | 1 |
| Gil, R | 1 |
| Grueso, J | 1 |
| Hernandez-Losa, J | 1 |
| Pujol, A | 1 |
| Moliné, T | 1 |
| Recio, JA | 1 |
| Kim, HJ | 1 |
| Jung, MH | 2 |
| Kim, H | 3 |
| El-Gamal, MI | 4 |
| Sim, TB | 1 |
| Lee, SH | 1 |
| Hong, JH | 2 |
| Hah, JM | 3 |
| Cho, JH | 1 |
| Choi, JH | 1 |
| Yoo, KH | 5 |
| Oh, CH | 5 |
| Karreth, FA | 1 |
| DeNicola, GM | 1 |
| Winter, SP | 1 |
| Tuveson, DA | 2 |
| Lee, J | 1 |
| Yu, H | 3 |
| Chung, JY | 1 |
| Sim, T | 3 |
| Aide, N | 1 |
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| McArthur, GA | 1 |
| Vaishampayan, UN | 1 |
| Burger, AM | 1 |
| Sausville, EA | 1 |
| Heilbrun, LK | 1 |
| Li, J | 1 |
| Horiba, MN | 1 |
| Egorin, MJ | 1 |
| Ivy, P | 1 |
| Pacey, S | 1 |
| Lorusso, PM | 1 |
| Augustine, CK | 1 |
| Toshimitsu, H | 1 |
| Jung, SH | 1 |
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| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours[NCT00982865] | Phase 1 | 182 participants (Actual) | Interventional | 2007-12-31 | Completed | ||
| 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) | Interventional | 2018-04-30 | Not 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 1 | 17 participants (Actual) | Interventional | 2006-11-08 | Completed | ||
| 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 2 | 14 participants (Actual) | Interventional | 2006-08-31 | Completed | ||
| A Phase I Expanded Cohort Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma[NCT01078961] | Phase 1 | 11 participants (Actual) | Interventional | 2010-09-30 | Completed | ||
| A Phase II Study of BAY 43-9006 (NSC 724772) in Unresectable Stage III and IV Melanoma (IND 69,869)[NCT00119249] | Phase 2 | 74 participants (Anticipated) | Interventional | 2005-06-30 | Completed | ||
| 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 2 | 83 participants (Actual) | Interventional | 2005-04-30 | Completed | ||
| Sorafenib Administered Using a High-dose, Pulsatile Regimen in Patients With Advanced Solid Malignancies: a Phase I Exposure Escalation Study[NCT02636426] | Phase 1 | 17 participants (Actual) | Interventional | 2015-09-30 | Completed | ||
| Phase II Trial of BAY 43-9006 (Sorafenib; NSC-724772) in Combination With Carboplatin and Paclitaxel in Patients With Metastatic Uveal Melanoma[NCT00329641] | Phase 2 | 25 participants (Actual) | Interventional | 2011-02-28 | Completed | ||
| 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 3 | 823 participants (Actual) | Interventional | 2005-06-30 | Completed | ||
| Randomized Phase II Trial Assessing the Combination of Nexavar® (Sorafenib), and Gemcitabine/Oxaliplatin in Patients Treated for Advanced (Unresectable/Metastatic) Hepatocellular Carcinoma.[NCT00941967] | Phase 2 | 78 participants (Actual) | Interventional | 2008-12-31 | Completed | ||
| 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 2 | 21 participants (Actual) | Interventional | 2012-02-22 | Completed | ||
| 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 2 | 101 participants (Actual) | Interventional | 2005-04-30 | Completed | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
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
| Intervention | Subjects (Number) |
|---|---|
| MSC1936369B Regimen 1 | 2 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 6 |
| MSC1936369B Regimen 3 Once Daily (QD) | 0 |
| MSC1936369B Regimen 3 Twice Daily | 6 |
(NCT00982865)
Timeframe: Baseline up to 253 weeks
| Intervention | Subjects (Number) |
|---|---|
| MSC1936369B Regimen 1 | 10 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 14 |
| MSC1936369B Regimen 3 Once Daily (QD) | 2 |
| MSC1936369B Regimen 3 Twice Daily | 2 |
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
| Intervention | Hours (h) (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 28 mg | 4.781 | 6.750 |
| MSC1936369B 3.5 mg | 3.346 | 4.985 |
| MSC1936369B 68 mg | 5.335 | 6.926 |
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
| Intervention | Hours (h) (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 120 mg | 5.247 | 3.964 | 3.038 |
| MSC1936369B 14 mg | 4.599 | 3.236 | 2.811 |
| MSC1936369B 45 mg | 5.389 | 4.688 | 2.931 |
| MSC1936369B 7 mg | 3.405 | 9.249 | 2.959 |
| MSC1936369B 94 mg | 5.351 | 5.672 | 2.842 |
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
| Intervention | Hour (h) (Geometric Mean) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 4.452 | 6.123 |
| MSC1936369B 90 mg | 4.898 | 4.534 |
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
| Intervention | Hours (h) (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 7 mg | 2.594 | 2.335 |
| MSC1936369B 14 mg | 5.119 | 4.443 |
| MSC1936369B 28 mg | 5.115 | 6.646 |
| MSC1936369B 45 mg | 4.187 | 5.277 |
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
| Intervention | Hours (h) (Geometric Mean) | |
|---|---|---|
| C1D15 | C3D1 | |
| MSC1936369B 5 mg | 2.941 | 2.732 |
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
| Intervention | Hours (h) (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 120 mg | 5.057 | 4.851 | 2.863 |
| MSC1936369B 150 mg | 4.904 | 5.479 | 2.418 |
| MSC1936369B 195 mg | 5.641 | 6.016 | 2.628 |
| MSC1936369B 68 mg | 3.305 | 6.441 | 3.477 |
| MSC1936369B 255 mg | 4.313 | 4.847 | 2.260 |
| MSC1936369B 94 mg | 4.826 | 5.193 | 2.853 |
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
| Intervention | Hour (h) (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 4.236 | 5.259 | 1.780 |
| MSC1936369B 90 mg | 4.097 | 5.599 | 2.680 |
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
| Intervention | Hour (h) (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 2.050 | 2.890 | 3.144 |
| MSC1936369B 60 mg | 2.509 | 3.265 | 2.636 |
| MSC1936369B 75 mg | 2.814 | 3.210 | 3.260 |
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
| Intervention | Liter (Geometric Mean) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 288.1 | 235.2 |
| MSC1936369B 90 mg | 402.4 | 393.6 |
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
| Intervention | Liter (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 14 mg | 473.32 | 555.9 |
| MSC1936369B 28 mg | 319.40 | 432.5 |
| MSC1936369B 45 mg | 331.36 | 378.0 |
| MSC1936369B 7 mg | 339.58 | 454.6 |
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
| Intervention | Liter (Geometric Mean) | |
|---|---|---|
| C1D15 | C3D1 | |
| MSC1936369B 5 mg | 252.7 | 352.10 |
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
| Intervention | Liter (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 120 mg | 361.12 | 646.9 | 201.39 |
| MSC1936369B 150 mg | 463.92 | 642.1 | 212.92 |
| MSC1936369B 195 mg | 440.55 | 464.2 | 274.24 |
| MSC1936369B 255 mg | 377.28 | 295.1 | 144.24 |
| MSC1936369B 68 mg | 366.00 | 406.6 | 206.07 |
| MSC1936369B 94 mg | 428.99 | 385.6 | 244.16 |
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
| Intervention | Liter (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 292.61 | 366.5 | 137.0 |
| MSC1936369B 90 mg | 336.38 | 507.7 | 292.5 |
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
| Intervention | Liter (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 339.51 | 297.9 | 571.8 |
| MSC1936369B 60 mg | 292.59 | 315.0 | 392.9 |
| MSC1936369B 75 mg | 340.43 | 437.6 | 362.6 |
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
| Intervention | Liter (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 28 mg | 336.32 | 365.1 |
| MSC1936369B 3.5 mg | 640.60 | 507.8 |
| MSC1936369B 68 mg | 307.90 | 357.8 |
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
| Intervention | Liter (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 120 mg | 361.99 | 351.4 | 316.63 |
| MSC1936369B 14 mg | 396.76 | 291.9 | 422.04 |
| MSC1936369B 45 mg | 378.56 | 333.9 | 348.19 |
| MSC1936369B 7 mg | 561.27 | 594.5 | 928.91 |
| MSC1936369B 94 mg | 389.49 | 416.3 | 438.91 |
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
| Intervention | Percentage of AUC 0-∞ (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 1.5 mg | 42.23 | 33.84 |
| MSC1936369B 68 mg | 4.08 | 6.56 |
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
| Intervention | Percentage of AUC 0-∞ (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 1 mg | 81.33 | 50.60 | 55.15 |
| MSC1936369B 120 mg | 5.28 | 2.97 | 26.05 |
| MSC1936369B 14 mg | 5.31 | 7.83 | 15.84 |
| MSC1936369B 2.5 mg | 43.45 | 40.60 | 55.79 |
| MSC1936369B 28 mg | 5.39 | 6.57 | 28.06 |
| MSC1936369B 3.5 mg | 26.80 | 21.27 | 32.85 |
| MSC1936369B 45 mg | 3.52 | 8.17 | 27.67 |
| MSC1936369B 7 mg | 13.08 | 19.82 | 21.27 |
| MSC1936369B 94 mg | 4.09 | 7.94 | 16.54 |
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
| Intervention | Percentage of AUC 0-∞ (Geometric Mean) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 1.74 | 9.96 |
| MSC1936369B 90 mg | 2.54 | 2.21 |
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
| Intervention | Percentage of AUC 0-∞ (Geometric Mean) |
|---|---|
| C1D15 | |
| MSC1936369B 1 mg | 40.86 |
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
| Intervention | Percentage of AUC 0-∞ (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 45 mg | 1.46 | 2.96 |
| MSC1936369B 14 mg | 12.17 | 12.45 |
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
| Intervention | Percentage of AUC 0-∞ (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 120 mg | 2.94 | 5.82 | 16.22 |
| MSC1936369B 150 mg | 2.64 | 4.82 | 17.54 |
| MSC1936369B 195 mg | 4.36 | 5.77 | 23.45 |
| MSC1936369B 2 mg | 55.78 | 33.34 | 33.93 |
| MSC1936369B 255 mg | 3.57 | 5.22 | 11.15 |
| MSC1936369B 28 mg | 3.29 | 6.89 | 26.32 |
| MSC1936369B 3.5 mg | 31.63 | 35.29 | 33.77 |
| MSC1936369B 5 mg | 27.25 | 21.93 | 17.27 |
| MSC1936369B 68 mg | 2.66 | 5.00 | 15.35 |
| MSC1936369B 7 mg | 15.10 | 19.45 | 20.68 |
| MSC1936369B 94 mg | 2.60 | 3.40 | 18.02 |
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
| Intervention | percentage of AUC 0-∞ (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 1.88 | 7.95 | 9.11 |
| MSC1936369B 90 mg | 2.11 | 4.28 | 17.56 |
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
| Intervention | Percentage of AUC 0-∞ (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 16.82 | 11.78 | 30.63 |
| MSC1936369B 60 mg | 7.70 | 14.14 | 16.43 |
| MSC1936369B 75 mg | 10.90 | 19.19 | 21.34 |
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
| Intervention | hour*ng/mL (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 1.5 mg | 6.2 | 9.4 |
| MSC1936369B 68 mg | 1699.7 | 2108.2 |
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
| Intervention | hour*ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 1 mg | 136.2 | 38.3 | 15.4 |
| MSC1936369B 120 mg | 2773.5 | 2022.8 | 3477.6 |
| MSC1936369B 14 mg | 234.1 | 206.3 | 134.5 |
| MSC1936369B 2.5 mg | 55.5 | 43.8 | 47.6 |
| MSC1936369B 28 mg | 574.2 | 805.6 | 489.8 |
| MSC1936369B 3.5 mg | 31.4 | 47.5 | 34.4 |
| MSC1936369B 45 mg | 924.2 | 960.7 | 1072.1 |
| MSC1936369B 7 mg | 61.3 | 105.6 | 55.5 |
| MSC1936369B 94 mg | 1836.4 | 2257.6 | 1056.0 |
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
| Intervention | hour*ng/mL (Geometric Mean) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 3344.3 | 5633.8 |
| MSC1936369B 90 mg | 1580.6 | 1495.7 |
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
| Intervention | hour*ng/mL (Geometric Mean) |
|---|---|
| C1D15 | |
| MSC1936369B 1 mg | 15.7 |
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
| Intervention | hour*ng/mL (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 45 mg | 820.4 | 933.9 |
| MSC1936369B 14 mg | 218.4 | 172.2 |
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
| Intervention | hour*ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 120 mg | 2424.2 | 2129.0 | 2461.3 |
| MSC1936369B 195 mg | 3602.2 | 3900.8 | 3452.9 |
| MSC1936369B 2 mg | 23.4 | 33.3 | 15.4 |
| MSC1936369B 255 mg | 4300.3 | 6232.1 | 5651.1 |
| MSC1936369B 28 mg | 646.9 | 669.1 | 415.6 |
| MSC1936369B 3.5 mg | 23.6 | 21.9 | 41.2 |
| MSC1936369B 150 mg | 2287.8 | 2029.9 | 2796.2 |
| MSC1936369B 5 mg | 59.1 | 102.0 | 49.5 |
| MSC1936369B 68 mg | 885.8 | 1665.2 | 1655.1 |
| MSC1936369B 7 mg | 90.3 | 89.7 | 58.1 |
| MSC1936369B 94 mg | 1525.6 | 1893.2 | 1584.8 |
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
| Intervention | hour*ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 1253.1 | 1753.9 | 1597.0 |
| MSC1936369B 90 mg | 1581.4 | 1517.1 | 1400.3 |
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
| Intervention | hour*ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 527.6 | 674.1 | 696.0 |
| MSC1936369B 60 mg | 742.3 | 1004.2 | 700.8 |
| MSC1936369B 75 mg | 939.9 | 978.4 | 1285.7 |
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
| Intervention | hour*ng/mL (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 14 mg | 188.4 | 161.5 |
| MSC1936369B 45 mg | 808.0 | 906.3 |
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
| Intervention | hour*ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 1 mg | 1.9 | 4.3 | 0.5 |
| MSC1936369B 120 mg | 2287.0 | 1862.3 | 2053.6 |
| MSC1936369B 150 mg | 2216.5 | 2086.6 | 2171.2 |
| MSC1936369B 195 mg | 3415.6 | 3436.8 | 2484.5 |
| MSC1936369B 2 mg | 8.2 | 22.2 | 10.2 |
| MSC1936369B 255 mg | 4041.3 | 5765.9 | 4906.3 |
| MSC1936369B 28 mg | 625.7 | 621.2 | 306.2 |
| MSC1936369B 3.5 mg | 6.7 | 13.8 | 26.2 |
| MSC1936369B 5 mg | 67.9 | 79.3 | 40.5 |
| MSC1936369B 68 mg | 861.1 | 1553.9 | 1394.7 |
| MSC1936369B 7 mg | 74.4 | 67.8 | 46.1 |
| MSC1936369B 94 mg | 1484.6 | 1826.2 | 1299.3 |
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
| Intervention | hour*nanogram per milliliter (h*ng/mL) (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 68 mg | 1624.8 | 1900.3 |
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
| Intervention | hour*nanogram per milliliter (h*ng/mL) (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 1.5 mg | 5.2 | 6.0 | 2.7 |
| MSC1936369B 120 mg | 2292.4 | 1682.4 | 2064.1 |
| MSC1936369B 14 mg | 213.9 | 182.0 | 113.2 |
| MSC1936369B 2.5 mg | 18.5 | 26.0 | 21.0 |
| MSC1936369B 28 mg | 531.3 | 691.9 | 334.9 |
| MSC1936369B 3.5 mg | 22.7 | 35.9 | 23.0 |
| MSC1936369B 45 mg | 889.0 | 880.0 | 666.3 |
| MSC1936369B 1 mg | 4.6 | 7.0 | 6.9 |
| MSC1936369B 7 mg | 52.7 | 83.6 | 45.2 |
| MSC1936369B 94 mg | 1748.1 | 1991.4 | 876.7 |
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
| Intervention | hour*ng/mL (Geometric Mean) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 3286 | 5072.9 |
| MSC1936369B 90 mg | 1509.6 | 1458.3 |
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
| Intervention | hour*ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 1229.3 | 1532.4 | 1392.3 |
| MSC1936369B 90 mg | 1544.9 | 1428.8 | 1122.5 |
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
| Intervention | hour*ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 407.2 | 589.3 | 450.0 |
| MSC1936369B 60 mg | 681.4 | 838.8 | 577.0 |
| MSC1936369B 75 mg | 791.1 | 710.3 | 1005.0 |
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
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 68 mg | 357.39 | 413.58 |
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
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 1 mg | 2.02 | 2.92 | 2.00 |
| MSC1936369B 1.5 mg | 3.20 | 2.69 | 2.90 |
| MSC1936369B 120 mg | 428.85 | 425.26 | 652.70 |
| MSC1936369B 14 mg | 62.32 | 54.47 | 51.30 |
| MSC1936369B 2.5 mg | 4.21 | 6.29 | 5.60 |
| MSC1936369B 28 mg | 126.21 | 150.67 | 84.70 |
| MSC1936369B 3.5 mg | 6.69 | 9.75 | 8.06 |
| MSC1936369B 45 mg | 212.96 | 175.94 | 167.75 |
| MSC1936369B 7 mg | 12.60 | 21.93 | 10.90 |
| MSC1936369B 94 mg | 325.99 | 602.12 | 282.44 |
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
| Intervention | ng/mL (Geometric Mean) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 1158.00 | 370.70 |
| MSC1936369B 90 mg | 321.14 | 305.94 |
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
| Intervention | ng/mL (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 14 mg | 39.19 | 34.87 |
| MSC1936369B 45 mg | 321.85 | 286.88 |
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
| Intervention | ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 120 mg | 605.11 | 492.81 | 568.49 |
| MSC1936369B 150 mg | 539.02 | 450.29 | 795.86 |
| MSC1936369B 195 mg | 680.87 | 629.85 | 773.14 |
| MSC1936369B 2 mg | 2.87 | 7.77 | 4.30 |
| MSC1936369B 255 mg | 990.92 | 1535.60 | 2344.91 |
| MSC1936369B 28 mg | 187.98 | 131.71 | 96.60 |
| MSC1936369B 3.5 mg | 4.55 | 4.21 | 6.56 |
| MSC1936369B 1 mg | 1.65 | 2.28 | 1.25 |
| MSC1936369B 5 mg | 17.26 | 18.78 | 14.81 |
| MSC1936369B 68 mg | 306.63 | 539.17 | 710.94 |
| MSC1936369B 7 mg | 30.90 | 18.47 | 16.10 |
| MSC1936369B 94 mg | 373.59 | 432.46 | 532.80 |
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
| Intervention | ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 241.27 | 316.08 | 473.27 |
| MSC1936369B 90 mg | 402.77 | 324.80 | 376.62 |
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
| Intervention | ng/mL (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 132.57 | 178.09 | 139.60 |
| MSC1936369B 60 mg | 206.46 | 231.12 | 157.46 |
| MSC1936369B 75 mg | 263.08 | 190.42 | 329.28 |
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])
| Intervention | Subjects (Number) | |||
|---|---|---|---|---|
| CR | PR | SD | PD | |
| MSC1936369B Regimen 1 | 0 | 0 | 19 | 20 |
| MSC1936369B Regimen 2 and Regimen 2 Food Effect | 0 | 4 | 34 | 33 |
| MSC1936369B Regimen 3 Once Daily (QD) | 0 | 2 | 9 | 4 |
| MSC1936369B Regimen 3 Twice Daily | 1 | 6 | 14 | 12 |
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
| Intervention | Subjects (Number) | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Haemoglobin decreased | Anaemia | Lymphopenia | Thrombocytopenia | Platelet count decreased | Neutropenia | Leukopenia | Pancytopenia | Hyponatraemia | Hypokalaemia | Hyperkalaemia | Hypocalcaemia | Hypercalcaemia | Hypomagnesaemia | Hypophosphataemia | Hepatic enzyme increased | Hepatic function abnormal | Alanine aminotransferase increased | Aspartate aminotransferase increased | Blood alkaline phosphatase increased | Hyperbilirubinaemia | Blood lactate dehydrogenase increased | Blood creatine phosphokinase increased | Blood creatinine increased | Blood 25-hydroxycholecalciferol decreased | Vitamin D decreased | Blood parathyroid hormone increased | Hyperglycaemia | C-reactive protein increased | Proteinuria | Hyperthyroidism | Hypoalbuminaemia | Weight increased | Weight decreased | Hyperthermia | Hypertension | Hypotension | Heart rate increased | Tachycardia | Blood potassium increased | |
| MSC1936369B Regimen 1 | 1 | 10 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 6 | 1 | 7 | 3 | 1 | 3 | 1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 2 | 23 | 7 | 6 | 1 | 4 | 0 | 0 | 1 | 10 | 0 | 7 | 3 | 3 | 2 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 4 | 3 | 8 | 5 | 5 | 1 | 0 | 0 | 0 |
| MSC1936369B Regimen 3 Once Daily (QD) | 0 | 3 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 4 | 0 | 1 | 2 | 0 | 2 | 0 |
| MSC1936369B Regimen 3 Twice Daily | 0 | 3 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1 | 0 | 1 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 3 | 2 | 1 | 4 | 0 | 0 | 0 | 0 |
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
| Intervention | Subjects (Number) | ||
|---|---|---|---|
| TEAEs | Serious TEAEs | TEAEs leading to discontinuation | |
| MSC1936369B Regimen 1 | 47 | 23 | 13 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 82 | 45 | 22 |
| MSC1936369B Regimen 3 Once Daily (QD) | 15 | 8 | 2 |
| MSC1936369B Regimen 3 Twice Daily | 34 | 21 | 6 |
(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
| Intervention | fold 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 Daily | 4.121 | 1.178 | 1.878 | 3.081 | 2.541 | 3.241 | 1.471 | 1.902 | 2.598 | 1.02 | 1.078 | 1.078 | 1.013 | 0.944 | 1.333 | 1.335 | 1.044 | 1.048 |
| MSC1936369B Regimen 3 Twice Daily | 3.629 | 1.249 | 1.821 | 2.069 | 2.235 | 2.16 | 1.315 | 1.98 | 2.043 | 1.086 | 1.079 | 1.098 | 1.108 | 1.049 | 1.047 | 1.059 | 1.026 | 1.068 |
(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
| Intervention | fold 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) | 3.937 | 1.305 | 3.422 | 1.454 | 2.411 | 2.868 | 3.265 | 1.293 | 1.653 | 2.476 | 3.716 | 1.288 | 2.688 | 1.075 | 1.069 | 1.012 | 1.095 | 1.13 | 1.108 | 1.118 | 1.125 | 1.041 | 1.045 | 1.138 | 1.251 | 1.052 |
(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
| Intervention | fold 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 1 | 4.524 | 1.235 | 3.828 | 1.454 | 2.853 | 2.722 | 4.48 | 3.257 | 1.252 | 1.514 | 2.768 | 5.179 | 1.795 | 3.106 | 1.1 | 1.063 | 1.059 | 1.058 | 1.075 | 1.163 | 1.233 | 1.223 | 1.04 | 0.994 | 1.047 | 1.074 | 1.087 | 0.674 |
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
| Intervention | Hours (h) (Median) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 68 mg | 1.000 | 1.000 |
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
| Intervention | Hours (h) (Median) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 1 mg | 1.500 | 1.633 | 1.52 |
| MSC1936369B 1.5 mg | 0.750 | 0.533 | 0.500 |
| MSC1936369B 120 mg | 1.017 | 1.083 | 2.000 |
| MSC1936369B 14 mg | 1.000 | 1.500 | 1.500 |
| MSC1936369B 2.5 mg | 1.500 | 1.000 | 1.52 |
| MSC1936369B 28 mg | 1.500 | 1.000 | 1.000 |
| MSC1936369B 3.5 mg | 1.500 | 1.000 | 1.000 |
| MSC1936369B 45 mg | 1.017 | 2.000 | 1.508 |
| MSC1936369B 7 mg | 1.500 | 1.017 | 1.517 |
| MSC1936369B 94 mg | 1.483 | 1.500 | 1.767 |
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
| Intervention | Hours (h) (Median) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 1.000 | 6.000 |
| MSC1936369B 90 mg | 1.600 | 2.033 |
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
| Intervention | Hours (h) (Median) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 14 mg | 1.500 | 1.500 |
| MSC1936369B 45 mg | 0.500 | 1.500 |
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
| Intervention | Hours (h) (Median) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 1 mg | 1.500 | 1.500 | 1.250 |
| MSC1936369B 120 mg | 1.250 | 2.000 | 1.042 |
| MSC1936369B 150 mg | 1.500 | 1.517 | 1.333 |
| MSC1936369B 195 mg | 1.250 | 1.250 | 1.000 |
| MSC1936369B 2 mg | 1.017 | 0.967 | 2.000 |
| MSC1936369B 255 mg | 2.000 | 1.458 | 1.000 |
| MSC1936369B 28 mg | 1.000 | 1.017 | 1.50 |
| MSC1936369B 3.5 mg | 1.500 | 2.000 | 1.258 |
| MSC1936369B 5 mg | 1.000 | 0.667 | 1.000 |
| MSC1936369B 68 mg | 1.000 | 1.250 | 0.500 |
| MSC1936369B 7 mg | 0.533 | 1.008 | 2.500 |
| MSC1936369B 94 mg | 1.500 | 1.500 | 2.000 |
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
| Intervention | Hours (h) (Median) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 1.033 | 2.500 | 2.000 |
| MSC1936369B 90 mg | 1.500 | 1.492 | 1.000 |
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
| Intervention | Hours (h) (Median) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 1.500 | 1.500 | 1.467 |
| MSC1936369B 60 mg | 1.000 | 1.500 | 1.183 |
| MSC1936369B 75 mg | 0.667 | 1.500 | 1.467 |
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
| Intervention | Liter per hour (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D12 | |
| MSC1936369B 28 mg | 48.76 | 37.49 |
| MSC1936369B 3.5 mg | 132.69 | 70.60 |
| MSC1936369B 68 mg | 40.01 | 35.80 |
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
| Intervention | Liter per hour (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D12 | C3D1 | |
| MSC1936369B 120 mg | 47.82 | 61.44 | 72.25 |
| MSC1936369B 14 mg | 59.80 | 62.53 | 104.07 |
| MSC1936369B 45 mg | 48.69 | 49.37 | 82.35 |
| MSC1936369B 7 mg | 114.26 | 44.55 | 217.56 |
| MSC1936369B 94 mg | 50.45 | 50.88 | 107.06 |
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
| Intervention | Liter per hour (Geometric Mean) | |
|---|---|---|
| Fasted | Fed | |
| MSC1936369B 150 mg | 44.85 | 26.62 |
| MSC1936369B 90 mg | 56.94 | 60.17 |
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
| Intervention | Liter per hour (Geometric Mean) | |
|---|---|---|
| C1D1 | C1D15 | |
| MSC1936369B 14 mg | 64.09 | 86.72 |
| MSC1936369B 28 mg | 43.28 | 45.10 |
| MSC1936369B 45 mg | 54.85 | 49.65 |
| MSC1936369B 7 mg | 90.76 | 134.9 |
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
| Intervention | Liter per hour (Geometric Mean) | |
|---|---|---|
| C1D15 | C3D1 | |
| MSC1936369B 5 mg | 59.55 | 89.34 |
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
| Intervention | Liter per hour (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 120 mg | 49.50 | 92.42 | 48.76 |
| MSC1936369B 150 mg | 65.57 | 81.22 | 61.04 |
| MSC1936369B 195 mg | 54.13 | 53.49 | 72.33 |
| MSC1936369B 255 mg | 60.63 | 42.20 | 44.23 |
| MSC1936369B 68 mg | 76.77 | 43.76 | 41.08 |
| MSC1936369B 94 mg | 61.61 | 51.47 | 59.31 |
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
| Intervention | Liter per hour (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 60 mg | 47.88 | 48.31 | 53.36 |
| MSC1936369B 90 mg | 56.91 | 62.85 | 75.63 |
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
| Intervention | Liter per hour (Geometric Mean) | ||
|---|---|---|---|
| C1D1 | C1D15 | C3D1 | |
| MSC1936369B 45 mg | 114.82 | 71.44 | 126.1 |
| MSC1936369B 60 mg | 80.83 | 66.89 | 103.3 |
| MSC1936369B 75 mg | 83.86 | 94.48 | 77.09 |
"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
| Intervention | participants (Number) |
|---|---|
| Bevacizumab and Sorafenib | 11 |
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)
| Intervention | days (Number) |
|---|---|
| Sorafenib + Dacarbazine | 420 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib + Dacarbazine | 255 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib + Dacarbazine | 327 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib + Dacarbazine | 93 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib + Dacarbazine | 259 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib + Dacarbazine | 102 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib + Dacarbazine | 102 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib + Dacarbazine | 48 |
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
| Intervention | participants (Number) | ||
|---|---|---|---|
| DC based on overall best response | DC at 6 months | DC at 12 months | |
| Sorafenib + Dacarbazine | 41 | 38 | 38 |
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
| Intervention | participants (Number) | ||||
|---|---|---|---|---|---|
| Overall response (CR+PR) | Complete response (CR) | Partial response (PR) | Stable disease (SD) | Progressive disease (PD) | |
| Sorafenib + Dacarbazine | 10 | 1 | 9 | 31 | 34 |
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
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| PFS at month 3 | PFS at month 6 | PFS at month 12 | |
| Sorafenib + Dacarbazine | 56.63 | 33.73 | 10.84 |
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
| Intervention | Percent of population (Number) |
|---|---|
| Sorafenib, Carboplatin, Paclitaxel | 29 |
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
| Intervention | Percentage of population (Number) |
|---|---|
| Sorafenib, Carboplatin, Paclitaxel | 42 |
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
| Intervention | participants (Number) |
|---|---|
| Sorafenib, Carboplatin, Paclitaxel | 0 |
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)
| Intervention | Participants with a given type of AE (Number) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Calcium, serum-low (hypocalcemia) | Cataract | Diarrhea | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Hemoglobin | Infec w/ Gr 3/4 neut-Urinary tract | Leukocytes (total WBC) | Lymphopenia | Mucositis/stomatitis (func/symp) - Pharynx | Neuropathy: sensory | Neutrophils/granulocytes (ANC/AGC) | Platelets | Pruritus/itching | Rash/desquamation | Vision-blurred vision | |
| Intervention | 1 | 1 | 2 | 1 | 1 | 2 | 1 | 4 | 2 | 1 | 2 | 10 | 4 | 1 | 5 | 1 |
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.
| Intervention | proportion (Number) |
|---|---|
| Arm I (Carboplatin + Paclitaxel + Sorafenib) | 0.205 |
| Arm II (Carboplatin + Paclitaxel+Placebo) | 0.182 |
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.
| Intervention | months (Median) |
|---|---|
| Arm I (Carboplatin + Paclitaxel + Sorafenib) | 11.1 |
| Arm II (Carboplatin + Paclitaxel+Placebo) | 11.3 |
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.
| Intervention | months (Median) |
|---|---|
| Arm I (Carboplatin + Paclitaxel + Sorafenib) | 4.9 |
| Arm II (Carboplatin + Paclitaxel+Placebo) | 4.2 |
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
| Intervention | Percentage of Participants (Number) |
|---|---|
| FCR With Lenalidomide | 45 |
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
| Intervention | Percentage of Participants (Number) |
|---|---|
| FCR With Lenalidomide | 95 |
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
| Intervention | scores on a scale (Mean) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | -0.015 |
| Placebo + Dacarbazine | -0.019 |
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
| Intervention | scores on a scale (Mean) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | -0.004 |
| Placebo + Dacarbazine | -0.008 |
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
| Intervention | scores on a scale (Mean) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | -2.00 |
| Placebo + Dacarbazine | -8.146 |
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
| Intervention | scores on a scale (Mean) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | 0.558 |
| Placebo + Dacarbazine | -4.425 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | 188 |
| Placebo + Dacarbazine | 161 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | 319 |
| Placebo + Dacarbazine | 359 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | 148 |
| Placebo + Dacarbazine | 82 |
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)
| Intervention | days (Median) |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | 148 |
| Placebo + Dacarbazine | 82 |
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
| Intervention | participants (Number) | |||
|---|---|---|---|---|
| missing | better | no change | worse | |
| Placebo + Dacarbazine | 1 | 2 | 34 | 13 |
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | 1 | 1 | 34 | 15 |
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
| Intervention | participants (Number) | ||||
|---|---|---|---|---|---|
| CR | PR | SD | PD | Not Evaluated | |
| Placebo + Dacarbazine | 0 | 6 | 22 | 21 | 1 |
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine | 0 | 12 | 24 | 15 | 0 |
15 reviews available for niacinamide and Melanoma
| Article | Year |
|---|---|
Nicotinamide for skin cancer chemoprevention.
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.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Com | 2017 |
Melanoma and nonmelanoma skin cancer chemoprevention: A role for nicotinamide?
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.
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.
Topics: Aged; Female; Humans; Male; Melanoma; Melanoma, Cutaneous Malignant; Middle Aged; Mitogen-Activated | 2015 |
[New molecular target therapy for thyroid neoplasms and malignant melanomas].
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Clinical Trials as Topic; Humans; Indoles; Ipilimumab | 2015 |
Metastatic melanoma: scientific rationale for sorafenib treatment and clinical results.
Topics: Antineoplastic Agents; Benzenesulfonates; Clinical Trials as Topic; Evidence-Based Medicine; Humans; | 2008 |
BRAF signaling and targeted therapies in melanoma.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; C | 2009 |
BRAF as therapeutic target in melanoma.
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?
Topics: Aged; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Basal Cell; Carcinoma, Renal Cell; Female | 2010 |
Sorafenib in melanoma.
Topics: Animals; Benzenesulfonates; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Melanoma | 2012 |
Sorafenib.
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.
Topics: Animals; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Renal Cell; Cell Transformation, Neopl | 2006 |
[Clinical studies with sorafenib (Nexavar) in metastatic melanoma].
Topics: Antineoplastic Agents; Benzenesulfonates; Clinical Trials as Topic; Humans; Melanoma; Niacinamide; P | 2007 |
Sorafenib: delivering a targeted drug to the right targets.
Topics: Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Clinical | 2007 |
26 trials available for niacinamide and Melanoma
| Article | Year |
|---|---|
Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial.
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.
Topics: Administration, Oral; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, al | 2019 |
Pimasertib-associated ophthalmological adverse events.
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).
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.
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.
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.
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.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Pro | 2014 |
A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma.
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.
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.
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Carboplatin; Cell Line, Tumor; Di | 2009 |
Safety, efficacy, pharmacokinetics, and pharmacodynamics of the combination of sorafenib and tanespimycin.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Benzoquinones; Clini | 2010 |
A phase II trial of sorafenib in metastatic melanoma with tissue correlates.
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.
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.
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.
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.
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).
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Extremities; Female; Follow-Up Studies; Humans; Male | 2012 |
Sorafenib in advanced melanoma: a critical role for pharmacokinetics?
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.
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Double-Blind Met | 2013 |
Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis.
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.
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.
Topics: Administration, Oral; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy | 2008 |
81 other studies available for niacinamide and Melanoma
| Article | Year |
|---|---|
Cutaneous immune-related adverse events and photodamaged skin in patients with metastatic melanoma: could nicotinamide be useful?
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.
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.
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.
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.
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.
Topics: Blood Vessels; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Gene Expression Profiling; Humans; | 2013 |
Innovations in the treatment of melanoma.
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.
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.
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.
Topics: Antineoplastic Agents; Benzazepines; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationshi | 2013 |
SIRT1 regulates lamellipodium extension and migration of melanoma cells.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates; Blotting, Western; Bre | 2008 |
Effectively targeting BRAF in melanoma: a formidable challenge.
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.
Topics: Aged, 80 and over; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Carcinoma, R | 2008 |
Searching for the Achilles' heel of melanoma cells: new treatment modalities.
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.
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.
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.
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.
Topics: Aged; Antineoplastic Agents; Anus Neoplasms; Benzenesulfonates; Dacarbazine; Humans; Male; Melanoma; | 2008 |
Targeting metastatic melanoma.
Topics: Antibodies, Monoclonal; Antigens, CD; Antineoplastic Agents; Benzenesulfonates; Cancer Vaccines; Cli | 2008 |
Molecular determinants of melanoma malignancy: selecting targets for improved efficacy of chemotherapy.
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.
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.
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.
Topics: Animals; Drug Discovery; Humans; Kidney; Melanoma; Metabolic Clearance Rate; Mice; Niacinamide; Posi | 2009 |
Rapid response to therapy of neurocutaneous melanosis with leptomeningeal melanoma.
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.
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.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates; Blotting, Wes | 2010 |
Synthesis and antiproliferative activity of pyrrolo[3,2-b]pyridine derivatives against melanoma.
Topics: Antineoplastic Agents; Benzenesulfonates; Cell Line; Humans; Melanoma; Niacinamide; Phenylurea Compo | 2010 |
C-Raf inhibits MAPK activation and transformation by B-Raf(V600E).
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.
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.
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.
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.
Topics: Adult; Aged; Antineoplastic Agents; Benzamides; Benzenesulfonates; Female; Humans; Imatinib Mesylate | 2010 |
Sorafenib, a multikinase inhibitor, enhances the response of melanoma to regional chemotherapy.
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.
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.
Topics: Antineoplastic Agents; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Benzenesulfonates; C | 2011 |
Oncogenic RAF: a brief history of time.
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.
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.
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.
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.
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.
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.
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.
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.
Topics: Animals; Antibodies; Antineoplastic Agents; Apoptosis; Autophagy; Benzamides; Benzenesulfonates; Cel | 2011 |
[News on melanoma from the 2010 Dermatology Days in Paris].
Topics: Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Biomarkers, Tumor; Chemotherapy, | 2011 |
Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates; | 2011 |
Setting up a kinase discovery and development project.
Topics: Adenosine Triphosphate; Animals; Crystallography, X-Ray; Drug Discovery; Drug Evaluation, Preclinica | 2012 |
Glutamatergic pathway targeting in melanoma: single-agent and combinatorial therapies.
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.
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.
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.
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.
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?
Topics: Adolescent; Antineoplastic Agents; Benzenesulfonates; Butadienes; Cell Survival; Dacarbazine; Drug T | 2011 |
Chemosensitivity of conjunctival melanoma cell lines to target-specific chemotherapeutic agents.
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.
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.
Topics: Animals; Carbohydrate Metabolism; Carcinoma, Ehrlich Tumor; Carcinoma, Krebs 2; Glycolysis; Melanoma | 1963 |
B-RAF is a therapeutic target in melanoma.
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.
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.
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).
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.
Topics: Androstadienes; Apoptosis; Benzenesulfonates; Blotting, Western; Cell Line, Tumor; Cell Proliferatio | 2007 |
Mutant V600E BRAF increases hypoxia inducible factor-1alpha expression in melanoma.
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.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Cell Movement; Cell Prol | 2007 |
GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines.
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.
Topics: Androstadienes; Apoptosis; Benzenesulfonates; Butadienes; Cell Line, Tumor; Cell Proliferation; Chro | 2008 |
Dramatic reduction of chronic lymphoedema of the lower limb with sorafenib therapy.
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.
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.
Topics: Adenocarcinoma; Animals; Carbon Dioxide; Emulsions; Female; Fluorocarbons; Humans; Hydrocarbons, Bro | 1996 |