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Erschienen in: Clinical Pharmacokinetics 11/2010

01.11.2010 | Review Article

Pharmacokinetic and Pharmacodynamic Perspectives on the Clinical Drug Development of Panitumumab

verfasst von: Dr Bing-Bing Yang, Peggy Lum, Alin Chen, Rosalin Arends, Lorin Roskos, Brian Smith, Juan José Pérez Ruixo

Erschienen in: Clinical Pharmacokinetics | Ausgabe 11/2010

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Abstract

Panitumumab is a recombinant, fully human IgG2 monoclonal antibody directed against the epidermal growth factor receptor (EGFR). It is indicated for use as monotherapy in the treatment of patients with EGFR-expressing metastatic colorectal cancer after disease progression with standard chemotherapy. The currently indicated dose is 6mg/kg given every 2 weeks.
Panitumumab is mainly distributed into the vascular space and exhibits nonlinear pharmacokinetics that are consistent with target-mediated drug disposition, involving saturable binding to EGFR and subsequent internalization and degradation inside the cells. Panitumumab is also cleared in a linear fashion by the reticuloendothelial system, similarly to other endogenous immunoglobulins. After single-dose administration of panitumumab as a 1-hour intravenous infusion, the area under the serum concentration-time curve increases in a greater-than-dose-proportional manner asthe dose increases from 0.75 to 5mg/kg; however, at doses above 2mg/kg, the exposure to panitumumab increases in a dose-proportional manner. Panitumumab pharmacokinetics are not meaningfully affected by the tumour type, EGFR membrane expression, tumour KRAS mutation, sex, age, race or renal or hepatic dysfunction. In addition, irinotecan-containing and paclitaxel/carboplatin-containing chemotherapeutic regimens do not appear to affect panitumumab pharmacokinetics. The results of population pharmacokinetic analyses have shown that bodyweight is the most influential covariate on panitumumab exposure, supporting the current use of bodyweight-adjusted doses (mg/kg). The relationship between the weekly dose of panitumumab and skin rash, an on-target pharmacodynamic effect of EGFR inhibition, reaches a plateau at 2.5 mg/kg, indicating that this is the optimal weekly dose. Two less-frequent dosing regimens (6 mg/kg given every 2 weeks and 9mg/kg given every 3 weeks) achieve steady-state serum trough concentrations similar to those achievedby 2.5mg/kg given every week, ensuring maximal EGFR coverage. Anti-panitumumab antibody production is uncommon and does not appear to have an impact on the pharmacokinetics of panitumumab.
Literatur
1.
Zurück zum Zitat Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001 Feb; 2(2): 127–37PubMedCrossRef Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001 Feb; 2(2): 127–37PubMedCrossRef
2.
Zurück zum Zitat Rowinsky EK. The erbB family: targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors. Annu Rev Med 2004 Feb; 55: 433–57PubMedCrossRef Rowinsky EK. The erbB family: targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors. Annu Rev Med 2004 Feb; 55: 433–57PubMedCrossRef
3.
Zurück zum Zitat Sibilia M, Kroismayr R, Lichtenberger B, et al. The epidermal growth factor receptor: from development to tumorigenesis. Differentiation 2007 Nov; 75(9): 770–87PubMedCrossRef Sibilia M, Kroismayr R, Lichtenberger B, et al. The epidermal growth factor receptor: from development to tumorigenesis. Differentiation 2007 Nov; 75(9): 770–87PubMedCrossRef
4.
Zurück zum Zitat Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005 May; 5(5): 341–54PubMedCrossRef Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005 May; 5(5): 341–54PubMedCrossRef
5.
Zurück zum Zitat Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res 2006 Sep 15; 12(18): 5268–72PubMedCrossRef Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res 2006 Sep 15; 12(18): 5268–72PubMedCrossRef
6.
Zurück zum Zitat Salomon DS, Brandt R, Ciardello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995 July; 19(3): 183–232PubMedCrossRef Salomon DS, Brandt R, Ciardello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995 July; 19(3): 183–232PubMedCrossRef
7.
Zurück zum Zitat Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 2005 Apr 10; 23(11): 2445–59PubMedCrossRef Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 2005 Apr 10; 23(11): 2445–59PubMedCrossRef
8.
Zurück zum Zitat Harari PM, Allen GW, Bonner JA. Biology of interactions: antiepidermal growth factor receptor agents. J Clin Oncol 2007 Sept 10; 25(6): 4057–65PubMedCrossRef Harari PM, Allen GW, Bonner JA. Biology of interactions: antiepidermal growth factor receptor agents. J Clin Oncol 2007 Sept 10; 25(6): 4057–65PubMedCrossRef
9.
Zurück zum Zitat Rivera F, Vega-Villegas ME, Lopez-Brea MF, et al. Current situation of panitumumab, matuzumab, nimotuzumab, and zalutumumab. Acta Oncol 2008 Jan; 47(1): 9–19PubMedCrossRef Rivera F, Vega-Villegas ME, Lopez-Brea MF, et al. Current situation of panitumumab, matuzumab, nimotuzumab, and zalutumumab. Acta Oncol 2008 Jan; 47(1): 9–19PubMedCrossRef
10.
Zurück zum Zitat Talavera A, Friemann R, Gómez-Puerta S, et al. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res 2009 Jul 15; 69(14): 5851–9PubMedCrossRef Talavera A, Friemann R, Gómez-Puerta S, et al. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res 2009 Jul 15; 69(14): 5851–9PubMedCrossRef
11.
Zurück zum Zitat Yang XD, Jia XC, Corvalan JR, et al. Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res 1999 Mar 15; 59(6): 1236–43PubMed Yang XD, Jia XC, Corvalan JR, et al. Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res 1999 Mar 15; 59(6): 1236–43PubMed
12.
Zurück zum Zitat Foon KA, Yang XD, Weiner LM, et al. Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 2004 Mar 1; 58(3): 984–90PubMedCrossRef Foon KA, Yang XD, Weiner LM, et al. Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 2004 Mar 1; 58(3): 984–90PubMedCrossRef
13.
Zurück zum Zitat Yang XD, Jia XC, Corvalan JR, et al. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 2001 Apr; 38(1): 17–23PubMedCrossRef Yang XD, Jia XC, Corvalan JR, et al. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 2001 Apr; 38(1): 17–23PubMedCrossRef
14.
Zurück zum Zitat Weiner LM, Belldegrun AS, Crawford J, et al. Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies. Clin Cancer Res 2008 Jan 15; 14(2): 502–8PubMedCrossRef Weiner LM, Belldegrun AS, Crawford J, et al. Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies. Clin Cancer Res 2008 Jan 15; 14(2): 502–8PubMedCrossRef
15.
Zurück zum Zitat Stephenson JJ, Gregory C, Burris H, et al. An open-label clinical trial evaluating safety and pharmacokinetics of two dosing schedules of panitumumab in patients with solid tumors. Clin Colorectal Cancer 2009 Jan; 8(1): 29–37PubMedCrossRef Stephenson JJ, Gregory C, Burris H, et al. An open-label clinical trial evaluating safety and pharmacokinetics of two dosing schedules of panitumumab in patients with solid tumors. Clin Colorectal Cancer 2009 Jan; 8(1): 29–37PubMedCrossRef
16.
Zurück zum Zitat Rowinsky EK, Schwartz GH, Gollob JA, et al. Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol 2004 Aug 1; 22(15): 3003–15PubMedCrossRef Rowinsky EK, Schwartz GH, Gollob JA, et al. Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol 2004 Aug 1; 22(15): 3003–15PubMedCrossRef
17.
Zurück zum Zitat Crawford J, Swanson P, Prager D, et al. Panitumumab, a fully human antibody, combined with paclitaxel and carboplatin versus paclitaxel and carboplatin alone for first-line advanced non-small-cell lung cancer (NSCLC): a primary analysis [abstract no. 1123]. European Journal of Cancer Supplements 2005; 3(2): 324 Crawford J, Swanson P, Prager D, et al. Panitumumab, a fully human antibody, combined with paclitaxel and carboplatin versus paclitaxel and carboplatin alone for first-line advanced non-small-cell lung cancer (NSCLC): a primary analysis [abstract no. 1123]. European Journal of Cancer Supplements 2005; 3(2): 324
18.
Zurück zum Zitat Hecht JR, Patnaik A, Berlin J, et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer 2007 Sep 1; 110(5): 980–8PubMedCrossRef Hecht JR, Patnaik A, Berlin J, et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer 2007 Sep 1; 110(5): 980–8PubMedCrossRef
19.
Zurück zum Zitat Berlin J, Posey J, Tchekmedyian S, et al. Panitumumab with irinotecan/ leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer. Clin Colorectal Cancer 2007 Mar; 6(6): 427–32PubMedCrossRef Berlin J, Posey J, Tchekmedyian S, et al. Panitumumab with irinotecan/ leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer. Clin Colorectal Cancer 2007 Mar; 6(6): 427–32PubMedCrossRef
21.
Zurück zum Zitat Hecht JR, Mitchell E, Neubauer MA, et al. Lack of correlation between epidermal growth factor receptor status and response to panitumumab monotherapy in metastatic colorectal cancer. Clin Cancer Res 2010 Apr 1; 16(7): 2205–13PubMedCrossRef Hecht JR, Mitchell E, Neubauer MA, et al. Lack of correlation between epidermal growth factor receptor status and response to panitumumab monotherapy in metastatic colorectal cancer. Clin Cancer Res 2010 Apr 1; 16(7): 2205–13PubMedCrossRef
22.
Zurück zum Zitat Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007 May 1; 25(13): 1658–64PubMedCrossRef Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007 May 1; 25(13): 1658–64PubMedCrossRef
23.
Zurück zum Zitat Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003 Jan; 3(1): 11–22PubMedCrossRef Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003 Jan; 3(1): 11–22PubMedCrossRef
24.
Zurück zum Zitat Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 2007 Apr; 7(4): 295–308PubMedCrossRef Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 2007 Apr; 7(4): 295–308PubMedCrossRef
25.
Zurück zum Zitat Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008 Apr 1; 26(10): 1626–34PubMedCrossRef Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008 Apr 1; 26(10): 1626–34PubMedCrossRef
26.
Zurück zum Zitat Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 2007 Mar 15; 67(6): 2643–8PubMedCrossRef Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 2007 Mar 15; 67(6): 2643–8PubMedCrossRef
27.
Zurück zum Zitat De Roock W, Piessevaux H, De Schutter J, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008 Mar; 19(3): 508–15PubMedCrossRef De Roock W, Piessevaux H, De Schutter J, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008 Mar; 19(3): 508–15PubMedCrossRef
28.
Zurück zum Zitat Vectibix® (panitumumab): package insert. Thousand Oaks (CA): Amgen Inc., 2010 Vectibix® (panitumumab): package insert. Thousand Oaks (CA): Amgen Inc., 2010
29.
Zurück zum Zitat Erbitux® (cetuximab): package insert. New York: ImClone LLC, and Princeton (NJ): Bristol-Myers Squibb, 2010 Mar Erbitux® (cetuximab): package insert. New York: ImClone LLC, and Princeton (NJ): Bristol-Myers Squibb, 2010 Mar
30.
Zurück zum Zitat Douillard J, Siena S, Cassidy J, et al. Randomized phase 3 study of panitumumab with FOLFOX4 vs FOLFOX4 alone as first-line treatment in patients with metastatic colorectal cancer: the PRIME trial [abstract no. LBA 10]. Annual Congress, European Cancer Organisation and European Society for Medical Oncology; 2009 Sep 20–24; Berlin Douillard J, Siena S, Cassidy J, et al. Randomized phase 3 study of panitumumab with FOLFOX4 vs FOLFOX4 alone as first-line treatment in patients with metastatic colorectal cancer: the PRIME trial [abstract no. LBA 10]. Annual Congress, European Cancer Organisation and European Society for Medical Oncology; 2009 Sep 20–24; Berlin
31.
Zurück zum Zitat Peeters M, Price T, Hotko Y, et al. Randomized phase 3 study of panitumumab with FOLFIRI vs FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer [abstract no. LBA 14]. Annual Congress, European Cancer Organisation and European Society for Medical Oncology; 2009 Sep 20–24; Berlin Peeters M, Price T, Hotko Y, et al. Randomized phase 3 study of panitumumab with FOLFIRI vs FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer [abstract no. LBA 14]. Annual Congress, European Cancer Organisation and European Society for Medical Oncology; 2009 Sep 20–24; Berlin
32.
Zurück zum Zitat Peeters M, Price T, Van Laethem J. Anti-epidermal growth factor receptor monotherapy in the treatment of metastatic colorectal cancer: where are we today? Oncologist 2009 Jan; 14(3): 29–39PubMedCrossRef Peeters M, Price T, Van Laethem J. Anti-epidermal growth factor receptor monotherapy in the treatment of metastatic colorectal cancer: where are we today? Oncologist 2009 Jan; 14(3): 29–39PubMedCrossRef
33.
Zurück zum Zitat Ma P, Yang BB, Wang YM, et al. Population pharmacokinetic analysis of panitumumab in patients with advanced solid tumors. J Clin Pharmacol 2009 Oct; 49(10): 1142–56PubMedCrossRef Ma P, Yang BB, Wang YM, et al. Population pharmacokinetic analysis of panitumumab in patients with advanced solid tumors. J Clin Pharmacol 2009 Oct; 49(10): 1142–56PubMedCrossRef
34.
Zurück zum Zitat Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res 1993 Jul; 10(7): 1093–5PubMedCrossRef Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res 1993 Jul; 10(7): 1093–5PubMedCrossRef
35.
Zurück zum Zitat Wiig H, Tenstad O. Interstitial exclusion of positively and negatively charged IgG in rat skin and muscle. Am J Physiol Heart Circ Physiol 2001 Apr; 280(4): H1505–12PubMed Wiig H, Tenstad O. Interstitial exclusion of positively and negatively charged IgG in rat skin and muscle. Am J Physiol Heart Circ Physiol 2001 Apr; 280(4): H1505–12PubMed
36.
Zurück zum Zitat Leveque D, Wisniewski S, Jehl F. Pharmacokinetics of therapeutic monoclonal antibodies used in oncology. Anticancer Res 2005 May–Jun; 25(3c): 2327–43PubMed Leveque D, Wisniewski S, Jehl F. Pharmacokinetics of therapeutic monoclonal antibodies used in oncology. Anticancer Res 2005 May–Jun; 25(3c): 2327–43PubMed
37.
Zurück zum Zitat Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 2004 Nov; 93(11): 2645–68PubMedCrossRef Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 2004 Nov; 93(11): 2645–68PubMedCrossRef
38.
Zurück zum Zitat Roskos LK, Davis CG, Schwab GM. The clinical pharmacology of therapeutic monoclonal antibodies. Drug Dev Res 2004; 61: 108–20CrossRef Roskos LK, Davis CG, Schwab GM. The clinical pharmacology of therapeutic monoclonal antibodies. Drug Dev Res 2004; 61: 108–20CrossRef
39.
Zurück zum Zitat Tabrizi MA, Tseng CM, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today 2006 Jan; 11(1–2): 81–8PubMedCrossRef Tabrizi MA, Tseng CM, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today 2006 Jan; 11(1–2): 81–8PubMedCrossRef
40.
Zurück zum Zitat Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2008 Nov; 84(5): 548–58PubMedCrossRef Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2008 Nov; 84(5): 548–58PubMedCrossRef
41.
Zurück zum Zitat Baselga J, Pfister D, Cooper MR, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cis-platin. J Clin Oncol 2000 Feb; 18(4): 904–14PubMed Baselga J, Pfister D, Cooper MR, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cis-platin. J Clin Oncol 2000 Feb; 18(4): 904–14PubMed
42.
Zurück zum Zitat Dirks NL, Nolting A, Kovar A, et al. Population pharmacokinetics of cetuximab in patients with squamous cell carcinoma of the head and neck. J Clin Pharmacol 2008 Mar; 48(3): 267–78PubMedCrossRef Dirks NL, Nolting A, Kovar A, et al. Population pharmacokinetics of cetuximab in patients with squamous cell carcinoma of the head and neck. J Clin Pharmacol 2008 Mar; 48(3): 267–78PubMedCrossRef
43.
Zurück zum Zitat Tan AR, Moore DF, Hidalgo M, et al. Pharmacokinetics of cetuximab after administration of escalating single dosing and weekly fixed dosing in patients with solid tumors. Clin Cancer Res 2006 Nov 1; 12(21): 6517–22PubMedCrossRef Tan AR, Moore DF, Hidalgo M, et al. Pharmacokinetics of cetuximab after administration of escalating single dosing and weekly fixed dosing in patients with solid tumors. Clin Cancer Res 2006 Nov 1; 12(21): 6517–22PubMedCrossRef
44.
Zurück zum Zitat Nolting A, Fox FE, Kovar A. Clinical drug development of cetixumab, a monoclonal antibody. In: Meibohm E, editor. Pharmacokinetics and pharmacodynamics of biotech drugs: principles and case studies in drug development. Weinheim: Wiley-VCH Verlag GmbH, 2006: 354–7 Nolting A, Fox FE, Kovar A. Clinical drug development of cetixumab, a monoclonal antibody. In: Meibohm E, editor. Pharmacokinetics and pharmacodynamics of biotech drugs: principles and case studies in drug development. Weinheim: Wiley-VCH Verlag GmbH, 2006: 354–7
45.
Zurück zum Zitat Waldmann TA, Strober W. Metabolism of immunoglobulins. Prog Allergy 1969; 13: 1–110PubMed Waldmann TA, Strober W. Metabolism of immunoglobulins. Prog Allergy 1969; 13: 1–110PubMed
47.
Zurück zum Zitat Arnold D, Hohler T, Dittrich C, et al. Cetuximab in combination with weekly 5-fluorouracil/folinic acid and oxaliplatin (FUFOX) in untreated patients with advanced colorectal cancer: a phase Ib/II study of the AIO GI Group. Ann Oncol 2008 Aug; 19(8): 1442–9PubMedCrossRef Arnold D, Hohler T, Dittrich C, et al. Cetuximab in combination with weekly 5-fluorouracil/folinic acid and oxaliplatin (FUFOX) in untreated patients with advanced colorectal cancer: a phase Ib/II study of the AIO GI Group. Ann Oncol 2008 Aug; 19(8): 1442–9PubMedCrossRef
48.
Zurück zum Zitat Delbaldo C, Pierga JY, Dieras V, et al. Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma. Eur J Cancer 2005 Aug; 41(12): 1739–45PubMedCrossRef Delbaldo C, Pierga JY, Dieras V, et al. Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma. Eur J Cancer 2005 Aug; 41(12): 1739–45PubMedCrossRef
49.
Zurück zum Zitat Lofgren JA, Dhandapani S, Pennucci JJ, et al. Comparing ELISA and surface plasmon resonance for assessing clinical immunogenicity of panitumumab. J Immunol 2007 June 1; 78(11): 7467–72 Lofgren JA, Dhandapani S, Pennucci JJ, et al. Comparing ELISA and surface plasmon resonance for assessing clinical immunogenicity of panitumumab. J Immunol 2007 June 1; 78(11): 7467–72
50.
51.
Zurück zum Zitat O’Neil BH, Allen R, Spigel DR, et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol 2007; 25: 3644–8PubMedCrossRef O’Neil BH, Allen R, Spigel DR, et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol 2007; 25: 3644–8PubMedCrossRef
52.
Zurück zum Zitat Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 2008; 358: 1109–17PubMedCrossRef Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 2008; 358: 1109–17PubMedCrossRef
53.
Zurück zum Zitat Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 2006 Oct; 6(10): 803–12PubMedCrossRef Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 2006 Oct; 6(10): 803–12PubMedCrossRef
54.
Zurück zum Zitat Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Targ Oncol 2009 May 19; 4(2): 107–19CrossRef Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Targ Oncol 2009 May 19; 4(2): 107–19CrossRef
55.
Zurück zum Zitat Baselga J. Skin as asurrogate tissue for pharmacodynamic end points: is it deep enough? Clin Cancer Res 2003 July; 9(7): 2389–90PubMed Baselga J. Skin as asurrogate tissue for pharmacodynamic end points: is it deep enough? Clin Cancer Res 2003 July; 9(7): 2389–90PubMed
56.
Zurück zum Zitat Perez-Soler R, Van Cutsem E. Clinical researchofEGFR inhibitors and related dermatologic toxicities. Oncology 2007 Oct; 21 (11 Suppl. 5): 10–6PubMed Perez-Soler R, Van Cutsem E. Clinical researchofEGFR inhibitors and related dermatologic toxicities. Oncology 2007 Oct; 21 (11 Suppl. 5): 10–6PubMed
57.
Zurück zum Zitat Perez-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 2005 Aug 1; 23(22): 5235–46PubMedCrossRef Perez-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 2005 Aug 1; 23(22): 5235–46PubMedCrossRef
58.
Zurück zum Zitat Peeters M, Siena S, Van Cutsem E, et al. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer 2009 Apr 1; 115(7): 1544–54PubMedCrossRef Peeters M, Siena S, Van Cutsem E, et al. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer 2009 Apr 1; 115(7): 1544–54PubMedCrossRef
59.
Zurück zum Zitat Segaert S, Tabernero J, Chosidow O, et al. The managementofskin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. J Dtsch Dermatol Ges 2005 Aug; 3(8): 599–606PubMedCrossRef Segaert S, Tabernero J, Chosidow O, et al. The managementofskin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. J Dtsch Dermatol Ges 2005 Aug; 3(8): 599–606PubMedCrossRef
60.
Zurück zum Zitat Shah NT, Kris MG, Pao W, et al. Practical management of patients with nonsmall-cell lung cancer treated with gefitinib. J Clin Oncol 2005 Jan 1; 23(1): 165–74PubMedCrossRef Shah NT, Kris MG, Pao W, et al. Practical management of patients with nonsmall-cell lung cancer treated with gefitinib. J Clin Oncol 2005 Jan 1; 23(1): 165–74PubMedCrossRef
61.
Zurück zum Zitat Fracasso PM, Burris H, Arquette MA, et al. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res 2007 Feb 1; 13(3): 986–93PubMedCrossRef Fracasso PM, Burris H, Arquette MA, et al. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res 2007 Feb 1; 13(3): 986–93PubMedCrossRef
Metadaten
Titel
Pharmacokinetic and Pharmacodynamic Perspectives on the Clinical Drug Development of Panitumumab
verfasst von
Dr Bing-Bing Yang
Peggy Lum
Alin Chen
Rosalin Arends
Lorin Roskos
Brian Smith
Juan José Pérez Ruixo
Publikationsdatum
01.11.2010
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 11/2010
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.2165/11535970-000000000-00000

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