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Erschienen in: Cancer Chemotherapy and Pharmacology 5/2015

01.11.2015 | Review Article

Personalizing chemotherapy dosing using pharmacological methods

verfasst von: Jai N. Patel, Apostolos Papachristos

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2015

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Abstract

Purpose

Given the toxic nature and narrow therapeutic index of traditional chemotherapeutics, better methods of dose and therapy selection are critical. Pharmacological methods, including pharmacogenomics and pharmacokinetics, offer a practical method to enrich drug exposure, reduce toxicity, and improve quality of life for patients.

Methods

PubMed and key abstracts from the American Society of Clinical Oncology (ASCO) and American Association for Cancer Research (AACR) were searched until July 2015 for clinical data relating to pharmacogenomic- and/or pharmacokinetic-guided dosing of anticancer drugs.

Results

Based on the results returned from a thorough search of the literature and the plausibility of utilizing pharmacogenomic and/or pharmacokinetic methods to personalize chemotherapy dosing, we identified several chemotherapeutic agents with the potential for therapy individualization. We highlight the available data, clinical validity, and utility of using pharmacogenomics to personalize therapy for tamoxifen, 5-fluorouracil, mercaptopurine, and irinotecan, in addition to using pharmacokinetics to personalize dosing for 5-fluorouracil, busulfan, methotrexate, taxanes, and topotecan.

Conclusion

A concerted effort should be made by researchers to further elucidate the role of pharmacological methods in personalizing chemotherapy dosing to optimize the risk–benefit profile. Clinicians should be aware of the clinical validity, utility, and availability of pharmacogenomic- and pharmacokinetic-guided therapies in clinical practice, to ultimately allow optimal dosing for each and every cancer patient.
Literatur
5.
Zurück zum Zitat Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, Levine RM, Lubiner ET, Reyes P, Schreiber FJ 3rd, Balducci L (2012) Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 118:3377–3386. doi:10.1002/cncr.26646 CrossRefPubMed Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, Levine RM, Lubiner ET, Reyes P, Schreiber FJ 3rd, Balducci L (2012) Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 118:3377–3386. doi:10.​1002/​cncr.​26646 CrossRefPubMed
8.
Zurück zum Zitat Rasmussen-Torvik LJ, Stallings SC, Gordon AS, Almoguera B, Basford MA, Bielinski SJ, Brautbar A, Brilliant MH, Carrell DS, Connolly JJ, Crosslin DR, Doheny KF, Gallego CJ, Gottesman O, Kim DS, Leppig KA, Li R, Lin S, Manzi S, Mejia AR, Pacheco JA, Pan V, Pathak J, Perry CL, Peterson JF, Prows CA, Ralston J, Rasmussen LV, Ritchie MD, Sadhasivam S, Scott SA, Smith M, Vega A, Vinks AA, Volpi S, Wolf WA, Bottinger E, Chisholm RL, Chute CG, Haines JL, Harley JB, Keating B, Holm IA, Kullo IJ, Jarvik GP, Larson EB, Manolio T, McCarty CA, Nickerson DA, Scherer SE, Williams MS, Roden DM, Denny JC (2014) Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems. Clin Pharmacol Ther 96:482–489. doi:10.1038/clpt.2014.137 PubMedCentralCrossRefPubMed Rasmussen-Torvik LJ, Stallings SC, Gordon AS, Almoguera B, Basford MA, Bielinski SJ, Brautbar A, Brilliant MH, Carrell DS, Connolly JJ, Crosslin DR, Doheny KF, Gallego CJ, Gottesman O, Kim DS, Leppig KA, Li R, Lin S, Manzi S, Mejia AR, Pacheco JA, Pan V, Pathak J, Perry CL, Peterson JF, Prows CA, Ralston J, Rasmussen LV, Ritchie MD, Sadhasivam S, Scott SA, Smith M, Vega A, Vinks AA, Volpi S, Wolf WA, Bottinger E, Chisholm RL, Chute CG, Haines JL, Harley JB, Keating B, Holm IA, Kullo IJ, Jarvik GP, Larson EB, Manolio T, McCarty CA, Nickerson DA, Scherer SE, Williams MS, Roden DM, Denny JC (2014) Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems. Clin Pharmacol Ther 96:482–489. doi:10.​1038/​clpt.​2014.​137 PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Hicks JK, Schwab M, Klein TE (2013) Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther 93:324–325. doi:10.1038/clpt.2013.4 PubMedCentralCrossRefPubMed Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Hicks JK, Schwab M, Klein TE (2013) Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther 93:324–325. doi:10.​1038/​clpt.​2013.​4 PubMedCentralCrossRefPubMed
10.
Zurück zum Zitat Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M (2013) Clinical pharmacogenetics implementation consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther 94:640–645. doi:10.1038/clpt.2013.172 PubMedCentralCrossRefPubMed Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M (2013) Clinical pharmacogenetics implementation consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther 94:640–645. doi:10.​1038/​clpt.​2013.​172 PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat Yu H, Steeghs N, Nijenhuis CM, Schellens JH, Beijnen JH, Huitema AD (2014) Practical guidelines for therapeutic drug monitoring of anticancer tyrosine kinase inhibitors: focus on the pharmacokinetic targets. Clin Pharmacokinet 53:305–325. doi:10.1007/s40262-014-0137-2 CrossRefPubMed Yu H, Steeghs N, Nijenhuis CM, Schellens JH, Beijnen JH, Huitema AD (2014) Practical guidelines for therapeutic drug monitoring of anticancer tyrosine kinase inhibitors: focus on the pharmacokinetic targets. Clin Pharmacokinet 53:305–325. doi:10.​1007/​s40262-014-0137-2 CrossRefPubMed
13.
Zurück zum Zitat Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30–39. doi:10.1093/jnci/dji005 CrossRefPubMed Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30–39. doi:10.​1093/​jnci/​dji005 CrossRefPubMed
16.
Zurück zum Zitat Schroth W, Hamann U, Fasching PA, Dauser S, Winter S, Eichelbaum M, Schwab M, Brauch H (2010) CYP2D6 polymorphisms as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification. Clin Cancer Res 16:4468–4477. doi:10.1158/1078-0432.CCR-10-0478 CrossRefPubMed Schroth W, Hamann U, Fasching PA, Dauser S, Winter S, Eichelbaum M, Schwab M, Brauch H (2010) CYP2D6 polymorphisms as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification. Clin Cancer Res 16:4468–4477. doi:10.​1158/​1078-0432.​CCR-10-0478 CrossRefPubMed
18.
Zurück zum Zitat Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Bolander J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302:1429–1436. doi:10.1001/jama.2009.1420 PubMedCentralCrossRefPubMed Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Bolander J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302:1429–1436. doi:10.​1001/​jama.​2009.​1420 PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat Province MA, Goetz MP, Brauch H, Flockhart DA, Hebert JM, Whaley R, Suman VJ, Schroth W, Winter S, Zembutsu H, Mushiroda T, Newman WG, Lee MT, Ambrosone CB, Beckmann MW, Choi JY, Dieudonne AS, Fasching PA, Ferraldeschi R, Gong L, Haschke-Becher E, Howell A, Jordan LB, Hamann U, Kiyotani K, Krippl P, Lambrechts D, Latif A, Langsenlehner U, Lorizio W, Neven P, Nguyen AT, Park BW, Purdie CA, Quinlan P, Renner W, Schmidt M, Schwab M, Shin JG, Stingl JC, Wegman P, Wingren S, Wu AH, Ziv E, Zirpoli G, Thompson AM, Jordan VC, Nakamura Y, Altman RB, Ames MM, Weinshilboum RM, Eichelbaum M, Ingle JN, Klein TE, International Tamoxifen Pharmacogenomics C (2014) CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clin Pharmacol Ther 95:216–227. doi:10.1038/clpt.2013.186 PubMedCentralCrossRefPubMed Province MA, Goetz MP, Brauch H, Flockhart DA, Hebert JM, Whaley R, Suman VJ, Schroth W, Winter S, Zembutsu H, Mushiroda T, Newman WG, Lee MT, Ambrosone CB, Beckmann MW, Choi JY, Dieudonne AS, Fasching PA, Ferraldeschi R, Gong L, Haschke-Becher E, Howell A, Jordan LB, Hamann U, Kiyotani K, Krippl P, Lambrechts D, Latif A, Langsenlehner U, Lorizio W, Neven P, Nguyen AT, Park BW, Purdie CA, Quinlan P, Renner W, Schmidt M, Schwab M, Shin JG, Stingl JC, Wegman P, Wingren S, Wu AH, Ziv E, Zirpoli G, Thompson AM, Jordan VC, Nakamura Y, Altman RB, Ames MM, Weinshilboum RM, Eichelbaum M, Ingle JN, Klein TE, International Tamoxifen Pharmacogenomics C (2014) CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clin Pharmacol Ther 95:216–227. doi:10.​1038/​clpt.​2013.​186 PubMedCentralCrossRefPubMed
20.
Zurück zum Zitat Irvin WJ Jr, Walko CM, Weck KE, Ibrahim JG, Chiu WK, Dees EC, Moore SG, Olajide OA, Graham ML, Canale ST, Raab RE, Corso SW, Peppercorn JM, Anderson SM, Friedman KJ, Ogburn ET, Desta Z, Flockhart DA, McLeod HL, Evans JP, Carey LA (2011) Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study. J Clin Oncol 29:3232–3239. doi:10.1200/JCO.2010.31.4427 PubMedCentralCrossRefPubMed Irvin WJ Jr, Walko CM, Weck KE, Ibrahim JG, Chiu WK, Dees EC, Moore SG, Olajide OA, Graham ML, Canale ST, Raab RE, Corso SW, Peppercorn JM, Anderson SM, Friedman KJ, Ogburn ET, Desta Z, Flockhart DA, McLeod HL, Evans JP, Carey LA (2011) Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study. J Clin Oncol 29:3232–3239. doi:10.​1200/​JCO.​2010.​31.​4427 PubMedCentralCrossRefPubMed
21.
Zurück zum Zitat Hertz DL, Snavely AC, Evans JP, Ibrahim JG, Anderson SM, Friedman KJ, Weck KE, et al. (2014) Does increasing the daily tamoxifen dose in patients with diminished CYP2D6 activity increase toxicity? J Clin Oncol 32:5 (suppl; abstr 561) Hertz DL, Snavely AC, Evans JP, Ibrahim JG, Anderson SM, Friedman KJ, Weck KE, et al. (2014) Does increasing the daily tamoxifen dose in patients with diminished CYP2D6 activity increase toxicity? J Clin Oncol 32:5 (suppl; abstr 561)
22.
Zurück zum Zitat Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP (2011) Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther 89:718–725. doi:10.1038/clpt.2011.32 PubMedCentralCrossRefPubMed Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP (2011) Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther 89:718–725. doi:10.​1038/​clpt.​2011.​32 PubMedCentralCrossRefPubMed
23.
Zurück zum Zitat Regan MM, Leyland-Jones B, Bouzyk M, Pagani O, Tang W, Kammler R, Dell’orto P, Biasi MO, Thurlimann B, Lyng MB, Ditzel HJ, Neven P, Debled M, Maibach R, Price KN, Gelber RD, Coates AS, Goldhirsch A, Rae JM, Viale G, Breast International Group 1-98 Collaborative G (2012) CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. J Natl Cancer Inst 104:441–451. doi:10.1093/jnci/djs125 PubMedCentralCrossRefPubMed Regan MM, Leyland-Jones B, Bouzyk M, Pagani O, Tang W, Kammler R, Dell’orto P, Biasi MO, Thurlimann B, Lyng MB, Ditzel HJ, Neven P, Debled M, Maibach R, Price KN, Gelber RD, Coates AS, Goldhirsch A, Rae JM, Viale G, Breast International Group 1-98 Collaborative G (2012) CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. J Natl Cancer Inst 104:441–451. doi:10.​1093/​jnci/​djs125 PubMedCentralCrossRefPubMed
24.
Zurück zum Zitat Rae JM, Drury S, Hayes DF, Stearns V, Thibert JN, Haynes BP, Salter J, Sestak I, Cuzick J, Dowsett M, ATAC trialists (2012) CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst 104:452–460. doi:10.1093/jnci/djs126 PubMedCentralCrossRefPubMed Rae JM, Drury S, Hayes DF, Stearns V, Thibert JN, Haynes BP, Salter J, Sestak I, Cuzick J, Dowsett M, ATAC trialists (2012) CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst 104:452–460. doi:10.​1093/​jnci/​djs126 PubMedCentralCrossRefPubMed
25.
Zurück zum Zitat Nakamura Y, Ratain MJ, Cox NJ, McLeod HL, Kroetz DL, Flockhart DA (2012) Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial. J Natl Cancer Inst 104:1264 (author reply 1266–1268). doi:10.1093/jnci/djs304 Nakamura Y, Ratain MJ, Cox NJ, McLeod HL, Kroetz DL, Flockhart DA (2012) Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial. J Natl Cancer Inst 104:1264 (author reply 1266–1268). doi:10.​1093/​jnci/​djs304
26.
Zurück zum Zitat Goetz MP, Sun JX, Suman VJ, Silva GO, Perou CM, Nakamura Y, Cox NJ, Stephens PJ, Miller VA, Ross JS, Chen D, Safgren SL, Kuffel MJ, Ames MM, Kalari KR, Gomez HL, Gonzalez-Angulo AM, Burgues O, Brauch HB, Ingle JN, Ratain MJ, Yelensky R (2015) Loss of heterozygosity at the CYP2D6 locus in breast cancer: implications for germline pharmacogenetic studies. J Natl Cancer Inst. doi:10.1093/jnci/dju401 Goetz MP, Sun JX, Suman VJ, Silva GO, Perou CM, Nakamura Y, Cox NJ, Stephens PJ, Miller VA, Ross JS, Chen D, Safgren SL, Kuffel MJ, Ames MM, Kalari KR, Gomez HL, Gonzalez-Angulo AM, Burgues O, Brauch HB, Ingle JN, Ratain MJ, Yelensky R (2015) Loss of heterozygosity at the CYP2D6 locus in breast cancer: implications for germline pharmacogenetic studies. J Natl Cancer Inst. doi:10.​1093/​jnci/​dju401
27.
Zurück zum Zitat Goetz MP, Suman VJ, Hoskin TL, Gnant M, Filipits M, Safgren SL, Kuffel M, Jakesz R, Rudas M, Greil R, Dietze O, Lang A, Offner F, Reynolds CA, Weinshilboum RM, Ames MM, Ingle JN (2013) CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8. Clin Cancer Res 19:500–507. doi:10.1158/1078-0432.CCR-12-2153 PubMedCentralCrossRefPubMed Goetz MP, Suman VJ, Hoskin TL, Gnant M, Filipits M, Safgren SL, Kuffel M, Jakesz R, Rudas M, Greil R, Dietze O, Lang A, Offner F, Reynolds CA, Weinshilboum RM, Ames MM, Ingle JN (2013) CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8. Clin Cancer Res 19:500–507. doi:10.​1158/​1078-0432.​CCR-12-2153 PubMedCentralCrossRefPubMed
28.
Zurück zum Zitat Saladores P, Murdter T, Eccles D, Chowbay B, Zgheib NK, Winter S, Ganchev B, Eccles B, Gerty S, Tfayli A, Lim JS, Yap YS, Ng RC, Wong NS, Dent R, Habbal MZ, Schaeffeler E, Eichelbaum M, Schroth W, Schwab M, Brauch H (2014) Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J. doi:10.1038/tpj.2014.34 PubMedCentralPubMed Saladores P, Murdter T, Eccles D, Chowbay B, Zgheib NK, Winter S, Ganchev B, Eccles B, Gerty S, Tfayli A, Lim JS, Yap YS, Ng RC, Wong NS, Dent R, Habbal MZ, Schaeffeler E, Eichelbaum M, Schroth W, Schwab M, Brauch H (2014) Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J. doi:10.​1038/​tpj.​2014.​34 PubMedCentralPubMed
32.
Zurück zum Zitat Van Kuilenburg AB, Meinsma R, Zoetekouw L, Van Gennip AH (2002) High prevalence of the IVS14 + 1G > A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity. Pharmacogenetics 12:555–558CrossRefPubMed Van Kuilenburg AB, Meinsma R, Zoetekouw L, Van Gennip AH (2002) High prevalence of the IVS14 + 1G > A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity. Pharmacogenetics 12:555–558CrossRefPubMed
33.
Zurück zum Zitat Schwab M, Zanger UM, Marx C, Schaeffeler E, Klein K, Dippon J, Kerb R, Blievernicht J, Fischer J, Hofmann U, Bokemeyer C, Eichelbaum M, German FUTSG (2008) Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group. J Clin Oncol 26:2131–2138. doi:10.1200/JCO.2006.10.4182 CrossRefPubMed Schwab M, Zanger UM, Marx C, Schaeffeler E, Klein K, Dippon J, Kerb R, Blievernicht J, Fischer J, Hofmann U, Bokemeyer C, Eichelbaum M, German FUTSG (2008) Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group. J Clin Oncol 26:2131–2138. doi:10.​1200/​JCO.​2006.​10.​4182 CrossRefPubMed
34.
Zurück zum Zitat Deenen MJ, Cats A, Sechterberger MK, Severens JL, Smits PHM, Bakker R, et al. (2011) Safety, pharmacokinetics (PK), and cost effectiveness of upfront genotyping of DPYD in fluoropyrimidine therapy. J Clin Oncol 29 (suppl; abstr 3606) Deenen MJ, Cats A, Sechterberger MK, Severens JL, Smits PHM, Bakker R, et al. (2011) Safety, pharmacokinetics (PK), and cost effectiveness of upfront genotyping of DPYD in fluoropyrimidine therapy. J Clin Oncol 29 (suppl; abstr 3606)
35.
Zurück zum Zitat Rosmarin D, Palles C, Church D, Domingo E, Jones A, Johnstone E, Wang H, Love S, Julier P, Scudder C, Nicholson G, Gonzalez-Neira A, Martin M, Sargent D, Green E, McLeod H, Zanger UM, Schwab M, Braun M, Seymour M, Thompson L, Lacas B, Boige V, Ribelles N, Afzal S, Enghusen H, Jensen SA, Etienne-Grimaldi MC, Milano G, Wadelius M, Glimelius B, Garmo H, Gusella M, Lecomte T, Laurent-Puig P, Martinez-Balibrea E, Sharma R, Garcia-Foncillas J, Kleibl Z, Morel A, Pignon JP, Midgley R, Kerr D, Tomlinson I (2014) Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: investigation in the QUASAR2 study, systematic review, and meta-analysis. J Clin Oncol 32:1031–1039. doi:10.1200/JCO.2013.51.1857 CrossRefPubMed Rosmarin D, Palles C, Church D, Domingo E, Jones A, Johnstone E, Wang H, Love S, Julier P, Scudder C, Nicholson G, Gonzalez-Neira A, Martin M, Sargent D, Green E, McLeod H, Zanger UM, Schwab M, Braun M, Seymour M, Thompson L, Lacas B, Boige V, Ribelles N, Afzal S, Enghusen H, Jensen SA, Etienne-Grimaldi MC, Milano G, Wadelius M, Glimelius B, Garmo H, Gusella M, Lecomte T, Laurent-Puig P, Martinez-Balibrea E, Sharma R, Garcia-Foncillas J, Kleibl Z, Morel A, Pignon JP, Midgley R, Kerr D, Tomlinson I (2014) Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: investigation in the QUASAR2 study, systematic review, and meta-analysis. J Clin Oncol 32:1031–1039. doi:10.​1200/​JCO.​2013.​51.​1857 CrossRefPubMed
37.
Zurück zum Zitat Morel A, Boisdron-Celle M, Fey L, Soulie P, Craipeau MC, Traore S, Gamelin E (2006) Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther 5:2895–2904. doi:10.1158/1535-7163.MCT-06-0327 CrossRefPubMed Morel A, Boisdron-Celle M, Fey L, Soulie P, Craipeau MC, Traore S, Gamelin E (2006) Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther 5:2895–2904. doi:10.​1158/​1535-7163.​MCT-06-0327 CrossRefPubMed
38.
Zurück zum Zitat McLeod HL, Lin JS, Scott EP, Pui CH, Evans WE (1994) Thiopurine methyltransferase activity in American white subjects and black subjects. Clin Pharmacol Ther 55:15–20CrossRefPubMed McLeod HL, Lin JS, Scott EP, Pui CH, Evans WE (1994) Thiopurine methyltransferase activity in American white subjects and black subjects. Clin Pharmacol Ther 55:15–20CrossRefPubMed
39.
Zurück zum Zitat McLeod HL, Krynetski EY, Relling MV, Evans WE (2000) Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia 14:567–572CrossRefPubMed McLeod HL, Krynetski EY, Relling MV, Evans WE (2000) Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia 14:567–572CrossRefPubMed
40.
Zurück zum Zitat Stanulla M, Schaeffeler E, Flohr T, Cario G, Schrauder A, Zimmermann M, Welte K, Ludwig WD, Bartram CR, Zanger UM, Eichelbaum M, Schrappe M, Schwab M (2005) Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA 293:1485–1489. doi:10.1001/jama.293.12.1485 CrossRefPubMed Stanulla M, Schaeffeler E, Flohr T, Cario G, Schrauder A, Zimmermann M, Welte K, Ludwig WD, Bartram CR, Zanger UM, Eichelbaum M, Schrappe M, Schwab M (2005) Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA 293:1485–1489. doi:10.​1001/​jama.​293.​12.​1485 CrossRefPubMed
41.
Zurück zum Zitat Schaeffeler E, Fischer C, Brockmeier D, Wernet D, Moerike K, Eichelbaum M, Zanger UM, Schwab M (2004) Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics 14:407–417CrossRefPubMed Schaeffeler E, Fischer C, Brockmeier D, Wernet D, Moerike K, Eichelbaum M, Zanger UM, Schwab M (2004) Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics 14:407–417CrossRefPubMed
42.
Zurück zum Zitat Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui CH, Evans WE (1999) Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 91:2001–2008CrossRefPubMed Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui CH, Evans WE (1999) Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 91:2001–2008CrossRefPubMed
43.
Zurück zum Zitat Stocco G, Cheok MH, Crews KR, Dervieux T, French D, Pei D, Yang W, Cheng C, Pui CH, Relling MV, Evans WE (2009) Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther 85:164–172. doi:10.1038/clpt.2008.154 PubMedCentralCrossRefPubMed Stocco G, Cheok MH, Crews KR, Dervieux T, French D, Pei D, Yang W, Cheng C, Pui CH, Relling MV, Evans WE (2009) Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther 85:164–172. doi:10.​1038/​clpt.​2008.​154 PubMedCentralCrossRefPubMed
44.
Zurück zum Zitat Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay N, Wong FL, Evans WE, Pui CH, Bhatia S, Relling MV (2015) Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol 33:1235–1242. doi:10.1200/JCO.2014.59.4671 CrossRefPubMed Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay N, Wong FL, Evans WE, Pui CH, Bhatia S, Relling MV (2015) Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol 33:1235–1242. doi:10.​1200/​JCO.​2014.​59.​4671 CrossRefPubMed
45.
Zurück zum Zitat Innocenti F, Ratain MJ (2003) Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology 17:52–55PubMed Innocenti F, Ratain MJ (2003) Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology 17:52–55PubMed
46.
Zurück zum Zitat Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A (2001) Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 7:2182–2194PubMed Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A (2001) Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 7:2182–2194PubMed
50.
Zurück zum Zitat Toffoli G, Cecchin E, Gasparini G, D’Andrea M, Azzarello G, Basso U, Mini E, Pessa S, De Mattia E, Lo Re G, Buonadonna A, Nobili S, De Paoli P, Innocenti F (2010) Genotype-driven phase I study of irinotecan administered in combination with fluorouracil/leucovorin in patients with metastatic colorectal cancer. J Clin Oncol 28:866–871. doi:10.1200/JCO.2009.23.6125 CrossRefPubMed Toffoli G, Cecchin E, Gasparini G, D’Andrea M, Azzarello G, Basso U, Mini E, Pessa S, De Mattia E, Lo Re G, Buonadonna A, Nobili S, De Paoli P, Innocenti F (2010) Genotype-driven phase I study of irinotecan administered in combination with fluorouracil/leucovorin in patients with metastatic colorectal cancer. J Clin Oncol 28:866–871. doi:10.​1200/​JCO.​2009.​23.​6125 CrossRefPubMed
51.
Zurück zum Zitat Marcuello E, Paez D, Pare L, Salazar J, Sebio A, del Rio E, Baiget M (2011) A genotype-directed phase I–IV dose-finding study of irinotecan in combination with fluorouracil/leucovorin as first-line treatment in advanced colorectal cancer. Br J Cancer 105:53–57. doi:10.1038/bjc.2011.206 PubMedCentralCrossRefPubMed Marcuello E, Paez D, Pare L, Salazar J, Sebio A, del Rio E, Baiget M (2011) A genotype-directed phase I–IV dose-finding study of irinotecan in combination with fluorouracil/leucovorin as first-line treatment in advanced colorectal cancer. Br J Cancer 105:53–57. doi:10.​1038/​bjc.​2011.​206 PubMedCentralCrossRefPubMed
52.
Zurück zum Zitat Innocenti F, Schilsky RL, Ramirez J, Janisch L, Undevia S, House LK, Das S, Wu K, Turcich M, Marsh R, Karrison T, Maitland ML, Salgia R, Ratain MJ (2014) Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer. J Clin Oncol 32:2328–2334. doi:10.1200/JCO.2014.55.2307 PubMedCentralCrossRefPubMed Innocenti F, Schilsky RL, Ramirez J, Janisch L, Undevia S, House LK, Das S, Wu K, Turcich M, Marsh R, Karrison T, Maitland ML, Salgia R, Ratain MJ (2014) Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer. J Clin Oncol 32:2328–2334. doi:10.​1200/​JCO.​2014.​55.​2307 PubMedCentralCrossRefPubMed
53.
Zurück zum Zitat Di Paolo A, Lencioni M, Amatori F, Di Donato S, Bocci G, Orlandini C, Lastella M, Federici F, Iannopollo M, Falcone A, Ricci S, Del Tacca M, Danesi R (2008) 5-fluorouracil pharmacokinetics predicts disease-free survival in patients administered adjuvant chemotherapy for colorectal cancer. Clin Cancer Res 14:2749–2755. doi:10.1158/1078-0432.CCR-07-1529 CrossRefPubMed Di Paolo A, Lencioni M, Amatori F, Di Donato S, Bocci G, Orlandini C, Lastella M, Federici F, Iannopollo M, Falcone A, Ricci S, Del Tacca M, Danesi R (2008) 5-fluorouracil pharmacokinetics predicts disease-free survival in patients administered adjuvant chemotherapy for colorectal cancer. Clin Cancer Res 14:2749–2755. doi:10.​1158/​1078-0432.​CCR-07-1529 CrossRefPubMed
54.
Zurück zum Zitat Patel JN, O’Neil BH, Deal AM, Ibrahim JG, Sherrill GB, Olajide OA, Atluri PM, Inzerillo JJ, Chay CH, McLeod HL, Walko CM (2014) A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil dosing for personalized colorectal cancer therapy. Oncologist 19:959–965. doi:10.1634/theoncologist.2014-0132 PubMedCentralCrossRefPubMed Patel JN, O’Neil BH, Deal AM, Ibrahim JG, Sherrill GB, Olajide OA, Atluri PM, Inzerillo JJ, Chay CH, McLeod HL, Walko CM (2014) A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil dosing for personalized colorectal cancer therapy. Oncologist 19:959–965. doi:10.​1634/​theoncologist.​2014-0132 PubMedCentralCrossRefPubMed
55.
Zurück zum Zitat Saif MW, Choma A, Salamone SJ, Chu E (2009) Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes. J Natl Cancer Inst 101:1543–1552. doi:10.1093/jnci/djp328 CrossRefPubMed Saif MW, Choma A, Salamone SJ, Chu E (2009) Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes. J Natl Cancer Inst 101:1543–1552. doi:10.​1093/​jnci/​djp328 CrossRefPubMed
56.
Zurück zum Zitat Gamelin E, Boisdron-Celle M, Delva R, Regimbeau C, Cailleux PE, Alleaume C, Maillet ML, Goudier MJ, Sire M, Person-Joly MC, Maigre M, Maillart P, Fety R, Burtin P, Lortholary A, Dumesnil Y, Picon L, Geslin J, Gesta P, Danquechin-Dorval E, Larra F, Robert J (1998) Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients. J Clin Oncol 16:1470–1478PubMed Gamelin E, Boisdron-Celle M, Delva R, Regimbeau C, Cailleux PE, Alleaume C, Maillet ML, Goudier MJ, Sire M, Person-Joly MC, Maigre M, Maillart P, Fety R, Burtin P, Lortholary A, Dumesnil Y, Picon L, Geslin J, Gesta P, Danquechin-Dorval E, Larra F, Robert J (1998) Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients. J Clin Oncol 16:1470–1478PubMed
57.
Zurück zum Zitat Fety R, Rolland F, Barberi-Heyob M, Hardouin A, Campion L, Conroy T, Merlin JL, Riviere A, Perrocheau G, Etienne MC, Milano G (1998) Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas. Clin Cancer Res 4:2039–2045PubMed Fety R, Rolland F, Barberi-Heyob M, Hardouin A, Campion L, Conroy T, Merlin JL, Riviere A, Perrocheau G, Etienne MC, Milano G (1998) Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas. Clin Cancer Res 4:2039–2045PubMed
58.
Zurück zum Zitat Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M (2008) Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol 26:2099–2105. doi:10.1200/JCO.2007.13.3934 CrossRefPubMed Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M (2008) Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol 26:2099–2105. doi:10.​1200/​JCO.​2007.​13.​3934 CrossRefPubMed
59.
Zurück zum Zitat Capitain O, Asevoaia A, Boisdron-Celle M, Poirier AL, Morel A, Gamelin E (2012) Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study. Clin Colorectal Cancer 11:263–267. doi:10.1016/j.clcc.2012.05.004 CrossRefPubMed Capitain O, Asevoaia A, Boisdron-Celle M, Poirier AL, Morel A, Gamelin E (2012) Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study. Clin Colorectal Cancer 11:263–267. doi:10.​1016/​j.​clcc.​2012.​05.​004 CrossRefPubMed
61.
Zurück zum Zitat Andersson BS, Thall PF, Madden T, Couriel D, Wang X, Tran HT, Anderlini P, de Lima M, 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 Transplant 8:477–485CrossRefPubMed Andersson BS, Thall PF, Madden T, Couriel D, Wang X, Tran HT, Anderlini P, de Lima M, 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 Transplant 8:477–485CrossRefPubMed
62.
Zurück zum Zitat 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 Transplant 14:220–228. doi:10.1016/j.bbmt.2007.10.028 CrossRefPubMed 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 Transplant 14:220–228. doi:10.​1016/​j.​bbmt.​2007.​10.​028 CrossRefPubMed
63.
Zurück zum Zitat Kangarloo SB, Naveed F, Ng ES, Chaudhry MA, Wu J, Bahlis NJ, Brown CB, Daly A, Duggan P, Geddes M, Quinlan D, Savoie ML, Shafey M, Stewart DA, Storek J, Yang M, Zacarias N, Yue P, Magliocco AM, Russell JA (2012) Development and validation of a test dose strategy for once-daily i.v. busulfan: importance of fixed infusion rate dosing. Biol Blood Marrow Transplant 18:295–301. doi:10.1016/j.bbmt.2011.07.015 CrossRefPubMed Kangarloo SB, Naveed F, Ng ES, Chaudhry MA, Wu J, Bahlis NJ, Brown CB, Daly A, Duggan P, Geddes M, Quinlan D, Savoie ML, Shafey M, Stewart DA, Storek J, Yang M, Zacarias N, Yue P, Magliocco AM, Russell JA (2012) Development and validation of a test dose strategy for once-daily i.v. busulfan: importance of fixed infusion rate dosing. Biol Blood Marrow Transplant 18:295–301. doi:10.​1016/​j.​bbmt.​2011.​07.​015 CrossRefPubMed
64.
Zurück zum Zitat Buffery PJ, Allen KM, Chin PK, Moore GA, Barclay ML, Begg EJ (2014) Thirteen years’ experience of pharmacokinetic monitoring and dosing of busulfan: can the strategy be improved? Ther Drug Monit 36:86–92. doi:10.1097/FTD.0b013e31829dc940 PubMed Buffery PJ, Allen KM, Chin PK, Moore GA, Barclay ML, Begg EJ (2014) Thirteen years’ experience of pharmacokinetic monitoring and dosing of busulfan: can the strategy be improved? Ther Drug Monit 36:86–92. doi:10.​1097/​FTD.​0b013e31829dc940​ PubMed
65.
Zurück zum Zitat Bartelink IH, Bredius RG, Belitser SV, Suttorp MM, Bierings M, Knibbe CA, Egeler M, Lankester AC, Egberts AC, Zwaveling J, Boelens JJ (2009) Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. Biol Blood Marrow Transplant 15:231–241. doi:10.1016/j.bbmt.2008.11.022 CrossRefPubMed Bartelink IH, Bredius RG, Belitser SV, Suttorp MM, Bierings M, Knibbe CA, Egeler M, Lankester AC, Egberts AC, Zwaveling J, Boelens JJ (2009) Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. Biol Blood Marrow Transplant 15:231–241. doi:10.​1016/​j.​bbmt.​2008.​11.​022 CrossRefPubMed
66.
Zurück zum Zitat Ansari M, Theoret Y, Rezgui MA, Peters C, Mezziani S, Desjean C, Vachon MF, Champagne MA, Duval M, Krajinovic M, Bittencourt H, Pediatric Disease Working Parties of the European B, Marrow Transplant G (2014) Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematopoietic stem cell transplantation. Ther Drug Monit 36:93–99. doi:10.1097/FTD.0b013e3182a04fc7 PubMed Ansari M, Theoret Y, Rezgui MA, Peters C, Mezziani S, Desjean C, Vachon MF, Champagne MA, Duval M, Krajinovic M, Bittencourt H, Pediatric Disease Working Parties of the European B, Marrow Transplant G (2014) Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematopoietic stem cell transplantation. Ther Drug Monit 36:93–99. doi:10.​1097/​FTD.​0b013e3182a04fc7​ PubMed
67.
Zurück zum Zitat Bartelink IH, van Reij EM, Gerhardt CE, van Maarseveen EM, de Wildt A, Versluys B, Lindemans CA, Bierings MB, Boelens JJ (2014) Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Biol Blood Marrow Transplant 20:345–353. doi:10.1016/j.bbmt.2013.11.027 CrossRefPubMed Bartelink IH, van Reij EM, Gerhardt CE, van Maarseveen EM, de Wildt A, Versluys B, Lindemans CA, Bierings MB, Boelens JJ (2014) Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Biol Blood Marrow Transplant 20:345–353. doi:10.​1016/​j.​bbmt.​2013.​11.​027 CrossRefPubMed
71.
Zurück zum Zitat Relling MV, Fairclough D, Ayers D, Crom WR, Rodman JH, Pui CH, Evans WE (1994) Patient characteristics associated with high-risk methotrexate concentrations and toxicity. J Clin Oncol 12:1667–1672PubMed Relling MV, Fairclough D, Ayers D, Crom WR, Rodman JH, Pui CH, Evans WE (1994) Patient characteristics associated with high-risk methotrexate concentrations and toxicity. J Clin Oncol 12:1667–1672PubMed
73.
Zurück zum Zitat Crews KR, Liu T, Rodriguez-Galindo C, Tan M, Meyer WH, Panetta JC, Link MP, Daw NC (2004) High-dose methotrexate pharmacokinetics and outcome of children and young adults with osteosarcoma. Cancer 100:1724–1733. doi:10.1002/cncr.20152 CrossRefPubMed Crews KR, Liu T, Rodriguez-Galindo C, Tan M, Meyer WH, Panetta JC, Link MP, Daw NC (2004) High-dose methotrexate pharmacokinetics and outcome of children and young adults with osteosarcoma. Cancer 100:1724–1733. doi:10.​1002/​cncr.​20152 CrossRefPubMed
74.
Zurück zum Zitat Fujita Y, Nakamura T, Aomori T, Nishiba H, Shinozaki H, Yanagawa T, Takagishi K, Watanabe H, Okada Y, Nakamura K, Horiuchi R, Yamamoto K (2010) Pharmacokinetic individualization of high-dose methotrexate chemotherapy for the treatment of localized osteosarcoma. J Chemother 22:186–190. doi:10.1179/joc.2010.22.3.186 CrossRefPubMed Fujita Y, Nakamura T, Aomori T, Nishiba H, Shinozaki H, Yanagawa T, Takagishi K, Watanabe H, Okada Y, Nakamura K, Horiuchi R, Yamamoto K (2010) Pharmacokinetic individualization of high-dose methotrexate chemotherapy for the treatment of localized osteosarcoma. J Chemother 22:186–190. doi:10.​1179/​joc.​2010.​22.​3.​186 CrossRefPubMed
75.
Zurück zum Zitat Trevino LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D, Chan D, Sparreboom A, Giacomini KM, Pui CH, Evans WE, Relling MV (2009) Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 27:5972–5978. doi:10.1200/JCO.2008.20.4156 PubMedCentralCrossRefPubMed Trevino LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D, Chan D, Sparreboom A, Giacomini KM, Pui CH, Evans WE, Relling MV (2009) Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 27:5972–5978. doi:10.​1200/​JCO.​2008.​20.​4156 PubMedCentralCrossRefPubMed
76.
Zurück zum Zitat Zgheib NK, Akra-Ismail M, Aridi C, Mahfouz R, Abboud MR, Solh H, Muwakkit SA (2014) Genetic polymorphisms in candidate genes predict increased toxicity with methotrexate therapy in Lebanese children with acute lymphoblastic leukemia. Pharmacogenet Genomics 24:387–396. doi:10.1097/FPC.0000000000000069 PubMed Zgheib NK, Akra-Ismail M, Aridi C, Mahfouz R, Abboud MR, Solh H, Muwakkit SA (2014) Genetic polymorphisms in candidate genes predict increased toxicity with methotrexate therapy in Lebanese children with acute lymphoblastic leukemia. Pharmacogenet Genomics 24:387–396. doi:10.​1097/​FPC.​0000000000000069​ PubMed
77.
Zurück zum Zitat Zhang HN, He XL, Wang C, Wang Y, Chen YJ, Li JX, Niu CH, Gao P (2014) Impact of SLCO1B1 521T > C variant on leucovorin rescue and risk of relapse in childhood acute lymphoblastic leukemia treated with high-dose methotrexate. Pediatr Blood Cancer 61:2203–2207. doi:10.1002/pbc.25191 CrossRefPubMed Zhang HN, He XL, Wang C, Wang Y, Chen YJ, Li JX, Niu CH, Gao P (2014) Impact of SLCO1B1 521T > C variant on leucovorin rescue and risk of relapse in childhood acute lymphoblastic leukemia treated with high-dose methotrexate. Pediatr Blood Cancer 61:2203–2207. doi:10.​1002/​pbc.​25191 CrossRefPubMed
78.
Zurück zum Zitat Radtke S, Zolk O, Renner B, Paulides M, Zimmermann M, Moricke A, Stanulla M, Schrappe M, Langer T (2013) Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia. Blood 121:5145–5153. doi:10.1182/blood-2013-01-480335 CrossRefPubMed Radtke S, Zolk O, Renner B, Paulides M, Zimmermann M, Moricke A, Stanulla M, Schrappe M, Langer T (2013) Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia. Blood 121:5145–5153. doi:10.​1182/​blood-2013-01-480335 CrossRefPubMed
80.
Zurück zum Zitat Huizing MT, Keung AC, Rosing H, van der Kuij V, ten Bokkel Huinink WW, Mandjes IM, Dubbelman AC, Pinedo HM, Beijnen JH (1993) Pharmacokinetics of paclitaxel and metabolites in a randomized comparative study in platinum-pretreated ovarian cancer patients. J Clin Oncol 11:2127–2135PubMed Huizing MT, Keung AC, Rosing H, van der Kuij V, ten Bokkel Huinink WW, Mandjes IM, Dubbelman AC, Pinedo HM, Beijnen JH (1993) Pharmacokinetics of paclitaxel and metabolites in a randomized comparative study in platinum-pretreated ovarian cancer patients. J Clin Oncol 11:2127–2135PubMed
81.
Zurück zum Zitat Gianni L, Kearns CM, Giani A, Capri G, Vigano L, Lacatelli A, Bonadonna G, Egorin MJ (1995) Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 13:180–190PubMed Gianni L, Kearns CM, Giani A, Capri G, Vigano L, Lacatelli A, Bonadonna G, Egorin MJ (1995) Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 13:180–190PubMed
82.
Zurück zum Zitat Huizing MT, Giaccone G, van Warmerdam LJ, Rosing H, Bakker PJ, Vermorken JB, Postmus PE, van Zandwijk N, Koolen MG, ten Bokkel Huinink WW, van der Vijgh WJ, Bierhorst FJ, Lai A, Dalesio O, Pinedo HM, Veenhof CH, Beijnen JH (1997) Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre. J Clin Oncol 15:317–329PubMed Huizing MT, Giaccone G, van Warmerdam LJ, Rosing H, Bakker PJ, Vermorken JB, Postmus PE, van Zandwijk N, Koolen MG, ten Bokkel Huinink WW, van der Vijgh WJ, Bierhorst FJ, Lai A, Dalesio O, Pinedo HM, Veenhof CH, Beijnen JH (1997) Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre. J Clin Oncol 15:317–329PubMed
83.
Zurück zum Zitat de Jonge ME, van den Bongard HJ, Huitema AD, Mathot RA, Rosing H, Baas P, van Zandwijk N, Beijnen JH, Schellens JH (2004) Bayesian pharmacokinetically guided dosing of paclitaxel in patients with non-small cell lung cancer. Clin Cancer Res 10:2237–2244CrossRefPubMed de Jonge ME, van den Bongard HJ, Huitema AD, Mathot RA, Rosing H, Baas P, van Zandwijk N, Beijnen JH, Schellens JH (2004) Bayesian pharmacokinetically guided dosing of paclitaxel in patients with non-small cell lung cancer. Clin Cancer Res 10:2237–2244CrossRefPubMed
84.
Zurück zum Zitat Sonnichsen DS, Hurwitz CA, Pratt CB, Shuster JJ, Relling MV (1994) Saturable pharmacokinetics and paclitaxel pharmacodynamics in children with solid tumors. J Clin Oncol 12:532–538PubMed Sonnichsen DS, Hurwitz CA, Pratt CB, Shuster JJ, Relling MV (1994) Saturable pharmacokinetics and paclitaxel pharmacodynamics in children with solid tumors. J Clin Oncol 12:532–538PubMed
85.
Zurück zum Zitat Woo MH, Relling MV, Sonnichsen DS, Rivera GK, Pratt CB, Pui CH, Evans WE, Pappo AS (1999) Phase I targeted systemic exposure study of paclitaxel in children with refractory acute leukemias. Clin Cancer Res 5:543–549PubMed Woo MH, Relling MV, Sonnichsen DS, Rivera GK, Pratt CB, Pui CH, Evans WE, Pappo AS (1999) Phase I targeted systemic exposure study of paclitaxel in children with refractory acute leukemias. Clin Cancer Res 5:543–549PubMed
86.
Zurück zum Zitat Mielke S, Sparreboom A, Steinberg SM, Gelderblom H, Unger C, Behringer D, Mross K (2005) Association of Paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer. Clin Cancer Res 11:4843–4850. doi:10.1158/1078-0432.CCR-05-0298 CrossRefPubMed Mielke S, Sparreboom A, Steinberg SM, Gelderblom H, Unger C, Behringer D, Mross K (2005) Association of Paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer. Clin Cancer Res 11:4843–4850. doi:10.​1158/​1078-0432.​CCR-05-0298 CrossRefPubMed
87.
Zurück zum Zitat Joerger M, Von Pawel J, Kraff S, Fischer JR, Eberhardt W, Gauler TC, Mueller L, Reinmuth N, Reck M, Kimmich M, Mayer F, et al (2015) Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin in advanced non-small cell lung cancer (NSCLC) patients. J Clin Oncol (suppl; abstr 8051) Joerger M, Von Pawel J, Kraff S, Fischer JR, Eberhardt W, Gauler TC, Mueller L, Reinmuth N, Reck M, Kimmich M, Mayer F, et al (2015) Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin in advanced non-small cell lung cancer (NSCLC) patients. J Clin Oncol (suppl; abstr 8051)
88.
Zurück zum Zitat Bruno R, Hille D, Riva A, Vivier N, ten Bokkel Huinnink WW, van Oosterom AT, Kaye SB, Verweij J, Fossella FV, Valero V, Rigas JR, Seidman AD, Chevallier B, Fumoleau P, Burris HA, Ravdin PM, Sheiner LB (1998) Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 16:187–196PubMed Bruno R, Hille D, Riva A, Vivier N, ten Bokkel Huinnink WW, van Oosterom AT, Kaye SB, Verweij J, Fossella FV, Valero V, Rigas JR, Seidman AD, Chevallier B, Fumoleau P, Burris HA, Ravdin PM, Sheiner LB (1998) Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 16:187–196PubMed
89.
Zurück zum Zitat Yamamoto N, Tamura T, Kamiya Y, Sekine I, Kunitoh H, Saijo N (2000) Correlation between docetaxel clearance and estimated cytochrome P450 activity by urinary metabolite of exogenous cortisol. J Clin Oncol 18:2301–2308PubMed Yamamoto N, Tamura T, Kamiya Y, Sekine I, Kunitoh H, Saijo N (2000) Correlation between docetaxel clearance and estimated cytochrome P450 activity by urinary metabolite of exogenous cortisol. J Clin Oncol 18:2301–2308PubMed
90.
Zurück zum Zitat Yamamoto N, Tamura T, Murakami H, Shimoyama T, Nokihara H, Ueda Y, Sekine I, Kunitoh H, Ohe Y, Kodama T, Shimizu M, Nishio K, Ishizuka N, Saijo N (2005) Randomized pharmacokinetic and pharmacodynamic study of docetaxel: dosing based on body-surface area compared with individualized dosing based on cytochrome P450 activity estimated using a urinary metabolite of exogenous cortisol. J Clin Oncol 23:1061–1069. doi:10.1200/JCO.2005.11.036 CrossRefPubMed Yamamoto N, Tamura T, Murakami H, Shimoyama T, Nokihara H, Ueda Y, Sekine I, Kunitoh H, Ohe Y, Kodama T, Shimizu M, Nishio K, Ishizuka N, Saijo N (2005) Randomized pharmacokinetic and pharmacodynamic study of docetaxel: dosing based on body-surface area compared with individualized dosing based on cytochrome P450 activity estimated using a urinary metabolite of exogenous cortisol. J Clin Oncol 23:1061–1069. doi:10.​1200/​JCO.​2005.​11.​036 CrossRefPubMed
91.
Zurück zum Zitat Engels FK, Loos WJ, van der Bol JM, de Bruijn P, Mathijssen RH, Verweij J, Mathot RA (2011) Therapeutic drug monitoring for the individualization of docetaxel dosing: a randomized pharmacokinetic study. Clin Cancer Res 17:353–362. doi:10.1158/1078-0432.CCR-10-1636 CrossRefPubMed Engels FK, Loos WJ, van der Bol JM, de Bruijn P, Mathijssen RH, Verweij J, Mathot RA (2011) Therapeutic drug monitoring for the individualization of docetaxel dosing: a randomized pharmacokinetic study. Clin Cancer Res 17:353–362. doi:10.​1158/​1078-0432.​CCR-10-1636 CrossRefPubMed
92.
Zurück zum Zitat Marsh S, Paul J, King CR, Gifford G, McLeod HL, Brown R (2007) Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised Trial in Ovarian Cancer. J Clin Oncol 25:4528–4535. doi:10.1200/JCO.2006.10.4752 CrossRefPubMed Marsh S, Paul J, King CR, Gifford G, McLeod HL, Brown R (2007) Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised Trial in Ovarian Cancer. J Clin Oncol 25:4528–4535. doi:10.​1200/​JCO.​2006.​10.​4752 CrossRefPubMed
93.
Zurück zum Zitat Marsh S, Somlo G, Li X, Frankel P, King CR, Shannon WD, McLeod HL, Synold TW (2007) Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 7:362–365. doi:10.1038/sj.tpj.6500434 CrossRefPubMed Marsh S, Somlo G, Li X, Frankel P, King CR, Shannon WD, McLeod HL, Synold TW (2007) Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 7:362–365. doi:10.​1038/​sj.​tpj.​6500434 CrossRefPubMed
94.
Zurück zum Zitat Morii K, Tanaka R, Takahashi Y, Kuwano R (1992) Cloning of cDNAs encoding human S-100 alpha and beta subunits and their differential expression in human tumor cell lines. J Neurosci Res 32:27–33. doi:10.1002/jnr.490320104 CrossRefPubMed Morii K, Tanaka R, Takahashi Y, Kuwano R (1992) Cloning of cDNAs encoding human S-100 alpha and beta subunits and their differential expression in human tumor cell lines. J Neurosci Res 32:27–33. doi:10.​1002/​jnr.​490320104 CrossRefPubMed
95.
Zurück zum Zitat Hahn NM, Marsh S, Fisher W, Langdon R, Zon R, Browning M, Johnson CS, Scott-Horton TJ, Li L, McLeod HL, Sweeney CJ (2006) Hoosier Oncology Group randomized phase II study of docetaxel, vinorelbine, and estramustine in combination in hormone-refractory prostate cancer with pharmacogenetic survival analysis. Clin Cancer Res 12:6094–6099. doi:10.1158/1078-0432.CCR-06-1188 CrossRefPubMed Hahn NM, Marsh S, Fisher W, Langdon R, Zon R, Browning M, Johnson CS, Scott-Horton TJ, Li L, McLeod HL, Sweeney CJ (2006) Hoosier Oncology Group randomized phase II study of docetaxel, vinorelbine, and estramustine in combination in hormone-refractory prostate cancer with pharmacogenetic survival analysis. Clin Cancer Res 12:6094–6099. doi:10.​1158/​1078-0432.​CCR-06-1188 CrossRefPubMed
96.
Zurück zum Zitat Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM, Byth K, Marsh S, McLeod H, Group AS, Harnett PR, Brown R, DeFazio A, Chenevix-Trench G (2008) ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res 14:5594–5601. doi:10.1158/1078-0432.CCR-08-0606 CrossRefPubMed Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM, Byth K, Marsh S, McLeod H, Group AS, Harnett PR, Brown R, DeFazio A, Chenevix-Trench G (2008) ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res 14:5594–5601. doi:10.​1158/​1078-0432.​CCR-08-0606 CrossRefPubMed
97.
Zurück zum Zitat Sissung TM, Danesi R, Price DK, Steinberg SM, de Wit R, Zahid M, Gaikwad N, Cavalieri E, Dahut WL, Sackett DL, Figg WD, Sparreboom A (2008) Association of the CYP1B1*3 allele with survival in patients with prostate cancer receiving docetaxel. Mol Cancer Ther 7:19–26. doi:10.1158/1535-7163.MCT-07-0557 CrossRefPubMed Sissung TM, Danesi R, Price DK, Steinberg SM, de Wit R, Zahid M, Gaikwad N, Cavalieri E, Dahut WL, Sackett DL, Figg WD, Sparreboom A (2008) Association of the CYP1B1*3 allele with survival in patients with prostate cancer receiving docetaxel. Mol Cancer Ther 7:19–26. doi:10.​1158/​1535-7163.​MCT-07-0557 CrossRefPubMed
98.
Zurück zum Zitat Stewart CF, Baker SD, Heideman RL, Jones D, Crom WR, Pratt CB (1994) Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hematologic toxicity. J Clin Oncol 12:1946–1954PubMed Stewart CF, Baker SD, Heideman RL, Jones D, Crom WR, Pratt CB (1994) Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hematologic toxicity. J Clin Oncol 12:1946–1954PubMed
99.
Zurück zum Zitat Zamboni WC, Bowman LC, Tan M, Santana VM, Houghton PJ, Meyer WH, Pratt CB, Heideman RL, Gajjar AJ, Pappo AS, Stewart CF (1999) Interpatient variability in bioavailability of the intravenous formulation of topotecan given orally to children with recurrent solid tumors. Cancer Chemother Pharmacol 43:454–460. doi:10.1007/s002800050923 CrossRefPubMed Zamboni WC, Bowman LC, Tan M, Santana VM, Houghton PJ, Meyer WH, Pratt CB, Heideman RL, Gajjar AJ, Pappo AS, Stewart CF (1999) Interpatient variability in bioavailability of the intravenous formulation of topotecan given orally to children with recurrent solid tumors. Cancer Chemother Pharmacol 43:454–460. doi:10.​1007/​s002800050923 CrossRefPubMed
100.
Zurück zum Zitat Santana VM, Zamboni WC, Kirstein MN, Tan M, Liu T, Gajjar A, Houghton PJ, Stewart CF (2003) A pilot study of protracted topotecan dosing using a pharmacokinetically guided dosing approach in children with solid tumors. Clin Cancer Res 9:633–640PubMed Santana VM, Zamboni WC, Kirstein MN, Tan M, Liu T, Gajjar A, Houghton PJ, Stewart CF (2003) A pilot study of protracted topotecan dosing using a pharmacokinetically guided dosing approach in children with solid tumors. Clin Cancer Res 9:633–640PubMed
101.
Zurück zum Zitat Stewart CF, Iacono LC, Chintagumpala M, Kellie SJ, Ashley D, Zamboni WC, Kirstein MN, Fouladi M, Seele LG, Wallace D, Houghton PJ, Gajjar A (2004) Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor. J Clin Oncol 22:3357–3365. doi:10.1200/JCO.2004.10.103 CrossRefPubMed Stewart CF, Iacono LC, Chintagumpala M, Kellie SJ, Ashley D, Zamboni WC, Kirstein MN, Fouladi M, Seele LG, Wallace D, Houghton PJ, Gajjar A (2004) Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor. J Clin Oncol 22:3357–3365. doi:10.​1200/​JCO.​2004.​10.​103 CrossRefPubMed
102.
Zurück zum Zitat Pawlik CA, Houghton PJ, Stewart CF, Cheshire PJ, Richmond LB, Danks MK (1998) Effective schedules of exposure of medulloblastoma and rhabdomyosarcoma xenografts to topotecan correlate with in vitro assays. Clin Cancer Res 4:1995–2002PubMed Pawlik CA, Houghton PJ, Stewart CF, Cheshire PJ, Richmond LB, Danks MK (1998) Effective schedules of exposure of medulloblastoma and rhabdomyosarcoma xenografts to topotecan correlate with in vitro assays. Clin Cancer Res 4:1995–2002PubMed
103.
Zurück zum Zitat Touw DJ, Neef C, Thomson AH, Vinks AA, Cost-Effectiveness of Therapeutic Drug Monitoring Committee of the International Association for Therapeutic Drug M, Clinical T (2005) Cost-effectiveness of therapeutic drug monitoring: a systematic review. Ther Drug Monit 27:10–17CrossRefPubMed Touw DJ, Neef C, Thomson AH, Vinks AA, Cost-Effectiveness of Therapeutic Drug Monitoring Committee of the International Association for Therapeutic Drug M, Clinical T (2005) Cost-effectiveness of therapeutic drug monitoring: a systematic review. Ther Drug Monit 27:10–17CrossRefPubMed
104.
Zurück zum Zitat de Jonge ME, Huitema AD, Schellens JH, Rodenhuis S, Beijnen JH (2005) Individualised cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation: a review. Clin Pharmacokinet 44:147–173. doi:10.2165/00003088-200544020-00002 CrossRefPubMed de Jonge ME, Huitema AD, Schellens JH, Rodenhuis S, Beijnen JH (2005) Individualised cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation: a review. Clin Pharmacokinet 44:147–173. doi:10.​2165/​00003088-200544020-00002 CrossRefPubMed
Metadaten
Titel
Personalizing chemotherapy dosing using pharmacological methods
verfasst von
Jai N. Patel
Apostolos Papachristos
Publikationsdatum
01.11.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 5/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2849-x

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