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Cancer Chemotherapy and Pharmacology

, Volume 74, Issue 5, pp 927–938 | Cite as

Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103)

  • Jan H. BeumerEmail author
  • Kouros Owzar
  • Lionel D. Lewis
  • Chen Jiang
  • Julianne L. Holleran
  • Susan M. Christner
  • William Blum
  • Steven Devine
  • Jonathan E. Kolitz
  • Charles Linker
  • Ravi Vij
  • Edwin P. Alyea
  • Richard A. Larson
  • Mark J. Ratain
  • Merrill J. Egorin
Original Article

Abstract

Purpose

Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome have often been excluded from myeloablative-conditioning regimens containing busulfan because of non-disease-related morbidity and mortality. We hypothesized that busulfan clearance (BuCL) in older patients (>60 years) would be reduced compared to that in younger patients, potentially explaining observed differences in busulfan tolerability.

Methods

AML patients in three CALGB hematopoietic cell transplantation studies were treated with a conditioning regimen using IV busulfan, dosed at 0.8 mg/kg. Plasma busulfan concentrations were determined by LC–MS and analyzed by non-compartmental methods. BuCL was normalized to actual (ABW), ideal (IBW), or corrected (CBW) body weight (kg). Differences in BuCL between age groups were examined using the Wilcoxon rank sum test.

Results

One hundred and eighty-five patients were accrued; 174 provided useable pharmacokinetic data. Twenty-nine patients ≥60 years old (median 66; range 60–74) had a significantly higher BuCL versus those <60 years old (median 50; range 18–60): BuCL 236 versus 168 mL/min, p = 0.0002; BuCL/ABW 3.0 versus 2.1 mL/min/kg, p = 0.0001; BuCL/IBW 3.8 versus 2.6 mL/min/kg, p = 0.0035; BuCL/CBW 3.4 versus 2.6 mL/min/kg, p = 0.0005. Inter-patient variability in clearance (CV %) was up to 48 % in both age groups. Phenytoin administration, a potential confounder, did not affect BuCL, regardless of weight normalization (p > 0.34).

Conclusions

Contrary to our hypothesis, BuCL was significantly higher in older patients compared to younger patients in these studies and does not explain the previously reported increase in busulfan toxicity observed in older patients.

Keywords

Busulfan Bone marrow transplant Elderly Pharmacokinetics 

Notes

Acknowledgments

We thank the University of Pittsburgh Cancer Institute Hematology/Oncology Writing Group for constructive suggestions regarding the manuscript. This project used the UPCI Clinical Pharmacology Analytical Facility (CPAF) and was supported in part by award P30CA047904 (Jan H. Beumer). (Alliance) was supported, in part, by grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, M.D., Chair) and to the Alliance Statistics and Data Center (Daniel J. Sargent, Ph.D., CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. The following institutions participated in this study: Christiana Care Health Services, Inc. CCOP, Wilmington, DE, Stephen Grubbs, M.D., supported by CA45418; Dana-Farber Cancer Institute, Boston, MA, Harold J. Burstein, M.D., Ph.D., supported by CA32291; Monter Cancer Center of North Shore—LIJ Health Systems, Lake Success, NY, Daniel Budman, MD, supported by CA35279; Massachusetts General Hospital, Boston, MA, Jeffrey W. Clark, M.D., supported by CA32291; Mount Sinai Medical Center, Miami, FL, Michael A. Schwartz, M.D., supported by CA45564; The Ohio State University Medical Center, Columbus, OH, Clara D. Bloomfield, M.D., supported by CA77658; Rhode Island Hospital, Providence, RI, William Sikov, M.D., supported by CA08025; Roswell Park Cancer Institute, Buffalo, NY, Ellis Levine, M.D., supported by CA59518; University of California at San Francisco, San Francisco, CA, Charles J. Ryan, M.D., supported by CA60138; University of Chicago, Chicago, IL, Hedy L. Kindler, M.D., supported by CA41287; University of Maryland Greenebaum Cancer Center, Baltimore, MD, Martin Edelman, M.D., supported by CA31983; University of Massachusetts Medical School, Worcester, MA, William V. Walsh, M.D., supported by CA37135; University of Minnesota, Minneapolis, MN, Bruce A. Peterson, M.D., supported by CA16450; University of Nebraska Medical Center, Omaha, NE, Apar Ganti, M.D., supported by CA77298; University of North Carolina at Chapel Hill, Chapel Hill, NC, Thomas C. Shea, M.D., supported by CA47559; University of Vermont, Burlington, VT, Steven M. Grunberg, M.D., supported by CA77406; Wake Forest University School of Medicine, Winston-Salem, NC, David D. Hurd, M.D., supported by CA03927; Washington University School of Medicine, St. Louis, MO, Nancy Bartlett, M.D., supported by CA77440; Weill Medical College of Cornell University, New York, NY, John Leonard, M.D., supported by CA07968; Western Pennsylvania Cancer Institute, Pittsburgh, PA, John Lister, M.D., supported by CA31946; Dartmouth Medical School-Norris Cotton Cancer Center, Lebanon, NH, Konstantin Dragnev, M.D., supported by CA04326; Walter Reed Army Medical Center, Washington, DC, David C. Van Echo, M.D., supported by CA26806.

Conflict of interest

None.

References

  1. 1.
    Chow SL, Lin Y, LoConte NK, Royds RB, Nekrassova TG, Ivy SP, Mauer J, Wilding G, Stoller R, Egorin MJ (2010) Enrollment of and toxicity in patients 70 years and older on CTEP/NCI-sponsored, single-agent phase I studies from 1980 to 2005. Proc Am Soc Clin Oncol 28:15sGoogle Scholar
  2. 2.
    Begg CB, Carbone PP (1983) Clinical trials and drug toxicity in the elderly. The experience of the Eastern Cooperative Oncology Group. Cancer 52(11):1986–1992PubMedCrossRefGoogle Scholar
  3. 3.
    Edwards BK, Howe HL, Ries LAG, Thun MJ, Rosenberg HM, Yancik R, Wingo PA, Jemal A, Feigal EG (2002) Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U.S. cancer burden. Cancer 94(10):2766–2792. doi: 10.1002/cncr.10593 PubMedCrossRefGoogle Scholar
  4. 4.
    McCune JS, Holmberg LA (2009) Busulfan in hematopoietic stem cell transplant setting. Expert Opin Drug Metabol Toxicol 5(8):957–969. doi: 10.1517/17425250903107764 CrossRefGoogle Scholar
  5. 5.
    Adelman LS, Liebman J (2011) Anatomy of body water and electrolytes. Am J Med 27:256–277CrossRefGoogle Scholar
  6. 6.
    Egorin MJ (1993) Cancer pharmacology in the elderly. Semin Oncol 20(1):43–49PubMedGoogle Scholar
  7. 7.
    Forbes GB, Reina JC (1970) Adult lean body mass declines with age: some longitudinal observations. Metabol Clin Exp 19(9):653–663CrossRefGoogle Scholar
  8. 8.
    Lindeman RD, Tobin J, Shock NW (1985) Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 33(4):278–285PubMedGoogle Scholar
  9. 9.
    Repetto L, Comandini D, Mammoliti S (2001) Life expectancy, comorbidity and quality of life: the treatment equation in the older cancer patients. Crit Rev Oncol Hematol 37(2):147–152PubMedCrossRefGoogle Scholar
  10. 10.
    Satariano WA, Ragland DR (1994) The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med 120(2):104–110PubMedCrossRefGoogle Scholar
  11. 11.
    Shock NW, Watkin DM, Yiengst MJ, Norris AH, Gaffney GW, Gregerman RI, Falzone JA (1963) Age differences in the water content of the body as related to basal oxygen consumption in males. J Gerontol 18:1–8PubMedCrossRefGoogle Scholar
  12. 12.
    Sotaniemi EA, Arranto AJ, Pelkonen O, Pasanen M (1997) Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 61(3):331–339. doi: 10.1016/S0009-9236(97)90166-1 PubMedCrossRefGoogle Scholar
  13. 13.
    Tumer N, Scarpace PJ, Lowenthal DT (1992) Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 32:271–302. doi: 10.1146/annurev.pa.32.040192.001415 PubMedCrossRefGoogle Scholar
  14. 14.
    Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V, Klapper S, Hansen K, Ramani R, Lachs M, Wong FL, Tew WP (2011) Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 29(25):3457–3465. doi: 10.1200/JCO.2011.34.7625 PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Alatrash G, de Lima M, Hamerschlak N, Pelosini M, Wang X, Xiao L, Kerbauy F, Chiattone A, Rondon G, Qazilbash MH, Giralt SA, de Padua Silva L, Hosing C, Kebriaei P, Zhang W, Nieto Y, Saliba RM, Champlin RE, Andersson BS (2011) Myeloablative reduced-toxicity i.v. busulfan-fludarabine and allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia or myelodysplastic syndrome in the sixth through eighth decades of life. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 17(10):1490–1496. doi: 10.1016/j.bbmt.2011.02.007
  16. 16.
    Cahn JY, Labopin M, Schattenberg A, Reiffers J, Willemze R, Zittoun R, Bacigalupo A, Prentice G, Gluckman E, Herve P, Gratwohl A, Gorin NC (1997) Allogeneic bone marrow transplantation for acute leukemia in patients over the age of 40 years. Acute leukemia working party of the european group for bone marrow transplantation (EBMT). Leukemia 11(3):416–419PubMedCrossRefGoogle Scholar
  17. 17.
    Ringden O, Labopin M, Ehninger G, Niederwieser D, Olsson R, Basara N, Finke J, Schwerdtfeger R, Eder M, Bunjes D, Gorin NC, Mohty M, Rocha V (2009) Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol 27(27):4570–4577. doi: 10.1200/JCO.2008.20.9692 PubMedCrossRefGoogle Scholar
  18. 18.
    Sutton L, Chastang C, Ribaud P, Jouet JP, Kuentz M, Attal M, Reiffers J, Tigaud JM, Rio B, Dauriac C, Legros M, Dreyfus F, Lioure B, Troussard X, Milpied N, Witz F, Oriol P, Cahn JY, Michallet M, Gluckman E, Ifrah N, Pico JL, Vilmer E, Leblond V (1996) Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Societe Francaise de Greffe de Moelle. Blood 88(1):358–365PubMedGoogle Scholar
  19. 19.
    Wallen H, Gooley TA, Deeg HJ, Pagel JM, Press OW, Appelbaum FR, Storb R, Gopal AK (2005) Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J Clin Oncol 23(15):3439–3446. doi: 10.1200/JCO.2005.05.694 PubMedCrossRefGoogle Scholar
  20. 20.
    Yusuf RZ, Dey B, Yeap BY, McAfee S, Attar E, Sepe PS, Dube C, Spitzer TR, Ballen KK (2009) Autologous SCT with a dose-reduced BU and CY regimen in older patients with non-Hodgkin’s lymphoma. Bone Marrow Transpl 43(1):37–42. doi: 10.1038/bmt.2008.298 CrossRefGoogle Scholar
  21. 21.
    Schuler US, Ehrsam M, Schneider A, Schmidt H, Deeg J, Ehninger G (1998) Pharmacokinetics of intravenous busulfan and evaluation of the bioavailability of the oral formulation in conditioning for haematopoietic stem cell transplantation. Bone Marrow Transpl 22(3):241–244. doi: 10.1038/sj.bmt.1701322 CrossRefGoogle Scholar
  22. 22.
    Veal GJ, Nguyen L, Paci A, Riggi M, Amiel M, Valteau-Couanet D, Brock P, Ladenstein R, Vassal G (2012) Busulfan pharmacokinetics following intravenous and oral dosing regimens in children receiving high-dose myeloablative chemotherapy for high-risk neuroblastoma as part of the HR-NBL-1/SIOPEN trial. Eur J Cancer 48(16):3063–3072. doi: 10.1016/j.ejca.2012.05.020 PubMedCrossRefGoogle Scholar
  23. 23.
    Grochow LB (1993) Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. Semin Oncol 20(4 Suppl 4):18-25; quiz 26Google Scholar
  24. 24.
    Andersson BS, Kashyap A, Gian V, Wingard JR, Fernandez H, Cagnoni PJ, Jones RB, Tarantolo S, Hu WW, Blume KG, Forman SJ, Champlin RE (2002) Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 8(3):145–154CrossRefGoogle Scholar
  25. 25.
    Andersson BS, Thall PF, Madden T, Couriel D, Wang X, Tran HT, Anderlini P, de LM, Gajewski J, Champlin RE (2002) Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia. Biol Blood Marrow Transpl 8(9):477–485Google Scholar
  26. 26.
    Devine SM, Ozwar K, Blum W, DeAngelo D, Stone RM, Hsu JW, Champlin RE, Chen YA, Vij R, Slack JL, Soiffer RJ, Larson RA, Shea TC, Hars V, Bennett E, Spangle S, Giralt SA, Carter SL, Horowitz MM, Linker C, Alyea EP (2012) A Phase II study of allogeneic transplantation for older patients with AML in first complete remission using a reduced intensity conditioning regimen: results from CALGB100103/BMT CTN 0502. Blood 120(21):230Google Scholar
  27. 27.
    Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA, Cancer, Leukemia Group B (2010) P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood 116(9):1413–1421. doi: 10.1182/blood-2009-07-229492 PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Robinson JD, Lupkiewicz SM, Palenik L, Lopez LM, Ariet M (1983) Determination of ideal body weight for drug dosage calculations. Am J Hosp Pharm 40(6):1016–1019PubMedGoogle Scholar
  29. 29.
    Ediss C, Tam YK (1995) An interactive computer program for determining areas bounded by drug concentration curves using lagrange interpolation. J Pharmacol Toxicol Methods 34(3):165–168PubMedCrossRefGoogle Scholar
  30. 30.
    Altman DG (1991) Practical statistics for medical research. Chapman & Hall, LondonGoogle Scholar
  31. 31.
    Bartelink IH, Boelens JJ, Bredius RG, Egberts AC, Wang C, Bierings MB, Shaw PJ, Nath CE, Hempel G, Zwaveling J, Danhof M, Knibbe CA (2012) Body weight-dependent pharmacokinetics of busulfan in paediatric haematopoietic stem cell transplantation patients: towards individualized dosing. Clin Pharmacokinet 51(5):331–345. doi: 10.2165/11598180-000000000-00000 PubMedCrossRefGoogle Scholar
  32. 32.
    Grochow LB, Krivit W, Whitley CB, Blazar B (1990) Busulfan disposition in children. Blood 75(8):1723–1727PubMedGoogle Scholar
  33. 33.
    Yeager AM, Wagner JE Jr, Graham ML, Jones RJ, Santos GW, Grochow LB (1992) Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation. Blood 80(9):2425–2428PubMedGoogle Scholar
  34. 34.
    McCune JS, Gooley T, Gibbs JP, Sanders JE, Petersdorf EW, Appelbaum FR, Anasetti C, Risler L, Sultan D, Slattery JT (2002) Busulfan concentration and graft rejection in pediatric patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 30(3):167–173. doi: 10.1038/sj.bmt.1703612 PubMedCrossRefGoogle Scholar
  35. 35.
    Dix SP, Wingard JR, Mullins RE, Jerkunica I, Davidson TG, Gilmore CE, York RC, Lin LS, Devine SM, Geller RB, Heffner LT, Hillyer CD, Holland HK, Winton EF, Saral R (1996) Association of busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant 17(2):225–230PubMedGoogle Scholar
  36. 36.
    Nguyen L, Fuller D, Lennon S, Leger F, Puozzo C (2004) I.V. busulfan in pediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients. Bone Marrow Transpl 33(10):979–987. doi: 10.1038/sj.bmt.1704446 CrossRefGoogle Scholar
  37. 37.
    Nguyen L, Leger F, Lennon S, Puozzo C (2006) Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study. Cancer ChemotherPharmacol 57(2):191–198. doi: 10.1007/s00280-005-0029-0 Google Scholar
  38. 38.
    Schechter T, Finkelstein Y, Doyle J, Verjee Z, Moretti M, Koren G, Dupuis LL (2007) Pharmacokinetic disposition and clinical outcomes in infants and children receiving intravenous busulfan for allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 13(3):307–314. doi: 10.1016/j.bbmt.2006.10.026 CrossRefGoogle Scholar
  39. 39.
    Vassal G, Challine D, Koscielny S, Hartmann O, Deroussent A, Boland I, Valteau-Couanet D, Lemerle J, Levi F, Gouyette A (1993) Chronopharmacology of high-dose busulfan in children. Cancer Res 53(7):1534–1537PubMedGoogle Scholar
  40. 40.
    Hazelton GA, Lang CA (1980) Glutathione contents of tissues in the aging mouse. Biochem J 188(1):25–30PubMedPubMedCentralGoogle Scholar
  41. 41.
    Loguercio C, Taranto D, Vitale LM, Beneduce F, Del Vecchio Blanco C (1996) Effect of liver cirrhosis and age on the glutathione concentration in the plasma, erythrocytes, and gastric mucosa of man. Free Radical Biol Med 20(3):483–488CrossRefGoogle Scholar
  42. 42.
    van Lieshout EM, Peters WH (1998) Age and gender dependent levels of glutathione and glutathione S-transferases in human lymphocytes. Carcinogenesis 19(10):1873–1875PubMedCrossRefGoogle Scholar
  43. 43.
    Pickering G, Schneider E, Papet I, Pujos-Guillot E, Pereira B, Simen E, Dubray C, Schoeffler P (2011) Acetaminophen metabolism after major surgery: a greater challenge with increasing age. Clin Pharmacol Ther 90(5):707–711. doi: 10.1038/clpt.2011.176 PubMedCrossRefGoogle Scholar
  44. 44.
    McCune JS, Bemer MJ, Barrett JS, Scott Baker K, Gamis AS, Holford NH (2014) Busulfan in infant to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and Bayesian dose personalization. Clin Cancer Res Off J Am Assoc Cancer Res 20(3):754–763. doi: 10.1158/1078-0432.CCR-13-1960 CrossRefGoogle Scholar
  45. 45.
    Andersson BS, Madden T, Tran HT, Hu WW, Blume KG, Chow DS, Champlin RE, Vaughan WP (2000) Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 6(5A):548–554CrossRefGoogle Scholar
  46. 46.
    Madden T, de Lima M, Thapar N, Nguyen J, Roberson S, Couriel D, Pierre B, Shpall EJ, Jones RB, Champlin RE, Andersson BS (2007) Pharmacokinetics of once-daily IV busulfan as part of pretransplantation preparative regimens: a comparison with an every 6-hour dosing schedule. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 13(1):56–64. doi: 10.1016/j.bbmt.2006.08.037 CrossRefGoogle Scholar
  47. 47.
    Geddes M, Kangarloo SB, Naveed F, Quinlan D, Chaudhry MA, Stewart D, Savoie ML, Bahlis NJ, Brown C, Storek J, Andersson BS, Russell JA (2008) High busulfan exposure is associated with worse outcomes in a daily i.v. busulfan and fludarabine allogeneic transplant regimen. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 14(2):220–228. doi: 10.1016/j.bbmt.2007.10.028 CrossRefGoogle Scholar
  48. 48.
    Ryu SG, Lee JH, Choi SJ, Lee JH, Lee YS, Seol M, Hur EH, Lee SH, Bae KS, Noh GJ, Lee MS, Yun SC, Han SB, Lee KH (2007) Randomized comparison of four-times-daily versus once-daily intravenous busulfan in conditioning therapy for hematopoietic cell transplantation. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 13(9):1095–1105. doi: 10.1016/j.bbmt.2007.06.005 CrossRefGoogle Scholar
  49. 49.
    Almog S, Kurnik D, Shimoni A, Loebstein R, Hassoun E, Gopher A, Halkin H, Nagler A (2011) Linearity and stability of intravenous busulfan pharmacokinetics and the role of glutathione in busulfan elimination. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 17(1):117–123. doi: 10.1016/j.bbmt.2010.06.017 CrossRefGoogle Scholar
  50. 50.
    Yeh RF, Pawlikowski MA, Blough DK, McDonald GB, O’Donnell PV, Rezvani A, Deeg HJ, McCune JS (2012) Accurate targeting of daily intravenous busulfan with 8-hour blood sampling in hospitalized adult hematopoietic cell transplant recipients. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 18(2):265–272. doi: 10.1016/j.bbmt.2011.06.013 CrossRefGoogle Scholar
  51. 51.
    Buggia I, Zecca M, Alessandrino EP, Locatelli F, Rosti G, Bosi A, Pession A, Rotoli B, Majolino I, Dallorso A, Regazzi MB (1996) Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. GITMO (Gruppo Italiano Trapianto di Midollo Osseo). Anticancer Res 16(4A):2083–2088PubMedGoogle Scholar
  52. 52.
    Nilsson C, Aschan J, Hentschke P, Ringden O, Ljungman P, Hassan M (2003) The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transpl 31(6):429–435. doi: 10.1038/sj.bmt.1703896 CrossRefGoogle Scholar
  53. 53.
    Meresse V, Hartmann O, Vassal G, Benhamou E, Valteau-Couanet D, Brugieres L, Lemerle J (1992) Risk factors for hepatic veno-occlusive disease after high-dose busulfan-containing regimens followed by autologous bone marrow transplantation: a study in 136 children. Bone Marrow Transpl 10(2):135–141Google Scholar
  54. 54.
    Hassan M, Oberg G, Bjorkholm M, Wallin I, Lindgren M (1993) Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics. Cancer Chemother Pharmacol 33(3):181–186PubMedCrossRefGoogle Scholar
  55. 55.
    Sandstrom M, Karlsson MO, Ljungman P, Hassan Z, Jonsson EN, Nilsson C, Ringden O, Oberg G, Bekassy A, Hassan M (2001) Population pharmacokinetic analysis resulting in a tool for dose individualization of busulphan in bone marrow transplantation recipients. Bone Marrow Transpl 28(7):657–664. doi: 10.1038/sj.bmt.1703229 CrossRefGoogle Scholar
  56. 56.
    Zhou SF (2008) Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab 9(4):310–322PubMedCrossRefGoogle Scholar
  57. 57.
    Gallagher EP, Sheehy KM (2001) Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. Toxicol Sci Off J Soc Toxicol 59(1):118–126CrossRefGoogle Scholar
  58. 58.
    Kostrubsky SE, Sinclair JF, Strom SC, Wood S, Urda E, Stolz DB, Wen YH, Kulkarni S, Mutlib A (2005) Phenobarbital and phenytoin increased acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes. Toxicol Sci Off J Soc Toxicol 87(1):146–155. doi: 10.1093/toxsci/kfi211 CrossRefGoogle Scholar
  59. 59.
    Ono H, Sakamoto A, Sakura N (2000) Plasma total glutathione concentrations in epileptic patients taking anticonvulsants. Clin Chim Acta 298(1–2):135–143PubMedCrossRefGoogle Scholar
  60. 60.
    Trame MN, Bergstrand M, Karlsson MO, Boos J, Hempel G (2011) Population pharmacokinetics of busulfan in children: increased evidence for body surface area and allometric body weight dosing of busulfan in children. Clin Cancer Res Off J Am Assoc Cancer Res 17(21):6867–6877. doi: 10.1158/1078-0432.CCR-11-0074 CrossRefGoogle Scholar
  61. 61.
    Zhang S, Pillai VC, Mada SR, Strom S, Venkataramanan R (2011) Effect of voriconazole and other azole antifungal agents on CYP3A activity and metabolism of tacrolimus in human liver microsomes. Xenobiotica Fate Foreign Comp Biol Syst. doi: 10.3109/00498254.2011.631224 Google Scholar
  62. 62.
    Pallis AG, Hatse S, Brouwers B, Pawelec G, Falandry C, Wedding U, Lago LD, Repetto L, Ring A, Wildiers H (2014) Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging? J Geriatr Oncol 5(2):204–218. doi: 10.1016/j.jgo.2013.09.001 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jan H. Beumer
    • 1
    • 2
    • 3
    • 16
    Email author
  • Kouros Owzar
    • 4
  • Lionel D. Lewis
    • 5
  • Chen Jiang
    • 4
  • Julianne L. Holleran
    • 2
  • Susan M. Christner
    • 2
  • William Blum
    • 6
  • Steven Devine
    • 6
  • Jonathan E. Kolitz
    • 7
  • Charles Linker
    • 8
  • Ravi Vij
    • 9
  • Edwin P. Alyea
    • 10
    • 11
    • 12
  • Richard A. Larson
    • 13
  • Mark J. Ratain
    • 13
  • Merrill J. Egorin
    • 2
    • 14
    • 15
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyUniversity of PittsburghPittsburghUSA
  2. 2.Cancer Therapeutics ProgramUniversity of Pittsburgh Cancer InstitutePittsburghUSA
  3. 3.Melanoma ProgramUniversity of Pittsburgh Cancer InstitutePittsburghUSA
  4. 4.Alliance Statistics and Data CenterDuke University Medical CenterDurhamUSA
  5. 5.Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical CenterThe Geisel School of Medicine at DartmouthHanoverUSA
  6. 6.Division of Hematology, James Cancer HospitalThe Ohio State UniversityColumbusUSA
  7. 7.Hofstra North Shore-LIJ School of MedicineLake SuccessUSA
  8. 8.University of California San FranciscoSan FranciscoUSA
  9. 9.Washington University School of MedicineSt LouisUSA
  10. 10.Medical OncologyDana-Farber Cancer InstituteBostonUSA
  11. 11.Department of MedicineBrigham and Women’s HospitalBostonUSA
  12. 12.Department of MedicineHarvard Medical SchoolBostonUSA
  13. 13.The University of ChicagoChicagoUSA
  14. 14.Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  15. 15.Division of Hematology/Oncology, Department of MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  16. 16.University of Pittsburgh Cancer CenterHillman Research PavilionPittsburghUSA

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