Sorafenib exposure decreases over time in patients with hepatocellular carcinoma
Tóm tắt
Background Intra-patient variability in sorafenib pharmacokinetics has been poorly investigated to date. We hypothesized that sorafenib clearance could decrease over time, as seen with imatinib. Patients and methods Sorafenib plasma concentrations were determined by liquid chromatography, every 2 weeks, in consecutive hepatocellular carcinoma patients treated with sorafenib. Sorafenib dose-normalized area under the concentration-time curve (AUC) was determined from a population pharmacokinetics model, and its kinetics was analyzed in order to identify possible alterations of exposure over time. Results Fifteen hepatocellular carcinoma patients with Child-Pugh A cirrhosis, in whom sorafenib dosing remained unchanged from initiation of treatment to disease progression, were eligible for this analysis. Sorafenib AUC significantly decreased over time: the median AUC during the third month of treatment was lower than that observed after one month of treatment (43.0 vs. 60.3 mg/L.h, p = 0.008). Most importantly, median sorafenib AUC at the time of progression was almost two-fold lower than that observed after one month of therapy (33.2 vs. 60.3 mg/L.h, p = 0.007). These findings suggest an induction of expression of efflux transporters in the gut wall, or an induction of sorafenib metabolism. Conclusions In patients with progressive disease in whom exposure markedly decreased from baseline, sorafenib dose escalation could be considered, aiming to restore an adequate drug exposure and possibly anti-tumor activity.
Tài liệu tham khảo
Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356(2):125–134
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390
Strumberg D, Clark JW, Awada A, Moore MJ, Richly H, Hendlisz A, Hirte HW, Eder JP, Lenz HJ, Schwartz B (2007) Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 12(4):426–437
Widmer N, Decosterd LA, Csajka C, Montemurro M, Haouala A, Leyvraz S, Buclin T (2010) Imatinib plasma levels: correlation with clinical benefit in GIST patients. Br J Cancer 102(7):1198–1199
Judson I, Ma P, Peng B, Verweij J, Racine A, di Paola ED, van Glabbeke M, Dimitrijevic S, Scurr M, Dumez H, van Oosterom A (2005) Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother Pharmacol 55(4):379–386
George S, Trent JC (2011) The role of imatinib plasma level testing in gastrointestinal stromal tumor. Cancer Chemother Pharmacol 67(Suppl 1):S45–50
Hislop J, Quayyum Z, Elders A, Fraser C, Jenkinson D, Mowatt G, Sharma P, Vale L, Petty R (2011) Clinical effectiveness and cost-effectiveness of imatinib dose escalation for the treatment of unresectable and/or metastatic gastrointestinal stromal tumours that have progressed on treatment at a dose of 400 mg/day: a systematic review and economic evaluation. Health Technol Assess 15(25):1–178
Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B (2010) Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer 46(13):2432–2440
Blanchet B, Billemont B, Cramard J, Benichou AS, Chhun S, Harcouet L, Ropert S, Dauphin A, Goldwasser F, Tod M (2009) Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice. J Pharm Biomed Anal 49(4):1109–1114
Tod M, Mir O, Bancelin N, Coriat R, Thomas-Schoemann A, Taieb F, Boudou-Rouquette P, Ropert S, Michels J, Abbas H, Durand JP, Dauphin A, Vidal M, Goldwasser F, Blanchet B (2011) Functional and clinical evidence of the influence of sorafenib binding to albumin on sorafenib disposition in adult cancer patients. Pharm Res. doi:10.1007/s11095-011-0499-1
Boudou-Rouquette P, Blanchet B, Mir O, Billemont B, Ropert S, Barete S, Coriat R, Franck N, Tod M, Goldwasser F (2010) Proposal of a new population pharmacokinetics (PK) model of sorafenib and rationale for a three-daily schedule. J Clin Oncol 28(15 suppl):3044
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216
Gnoth MJ, Sandmann S, Engel K, Radtke M (2010) In vitro to in vivo comparison of the substrate characteristics of sorafenib tosylate toward P-glycoprotein. Drug Metab Dispos 38(8):1341–1346
Lagas JS, van Waterschoot RA, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH (2010) Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther 9(2):319–326
Burger H, van Tol H, Brok M, Wiemer EA, de Bruijn EA, Guetens G, de Boeck G, Sparreboom A, Verweij J, Nooter K (2005) Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther 4(7):747–752
Pressiani T, Rimassa L, Boni LR, Fagiuoli S, Ardizzoni A, Foa P, Cortesi E, Porta C, Artioli F, Latini L, Carnaghi C, Lutman RF, Torzilli G, Tommasini M, Ceriani R, Covini G, Giordano L, Locopo N, Santoro A (2011) Phase II randomized trial on dose-escalated sorafenib (S) versus best supportive care (BSC) in patients with advanced hepatocellular carcinoma (HCC) with disease progression on prior S treatment. J Clin Oncol 29:4115
Semrad TJ, Gandara DR, Lara PN Jr (2011) Enhancing the clinical activity of sorafenib through dose escalation: rationale and current experience. Ther Adv Med Oncol 3(2):95–100