Breast Cancer Research and Treatment

, Volume 148, Issue 1, pp 197–209 | Cite as

Lapatinib-associated mucocutaneous toxicities are clinical predictors of improved progression-free survival in patients with human epidermal growth factor receptor (HER2)-positive advanced breast cancer

  • Kazuhiro Araki
  • Ippei Fukada
  • Rie Horii
  • Shunji Takahashi
  • Futoshi Akiyama
  • Takuji Iwase
  • Yoshinori Ito
Epidemiology
First Online:
Received:
Accepted:

Abstract

This study is aimed to identify clinical predictors, other than HER2 overexpression, for the response to lapatinib plus capecitabine (LAPCAP) in patients with HER2-positive advanced breast cancer (HER2ABC). Data from our medical records of 76 patients from June 2009 to March 2013 were analyzed. Evaluations of these patients with HER2ABC treated with LAPCAP included baseline characteristics, dose modifications, efficacy, and incidence of adverse events (AEs). With a median follow-up of 20 months, the median number of prior therapies for ABC before LAPCAP was 2 (range 0–13), and 66 patients had previously received trastuzumab. For LAPCAP, the overall response rate was 21 %, and the clinical benefit rate was 60 %. During the initial 12-month observation period, 93 % of patients had AEs. The most common AE was hand-foot syndrome (HFS) in 55 patients. Progression-free survival (PFS) was better in patients who had HFS than in those who did not (p = 0.0002). Since HFS is a well-known AE associated with CAP, whether CAP dose affected PFS or not was investigated, but no positive relationship was found. Since several studies with EGFR-targeted agents have suggested a positive correlation between cutaneous toxicities and outcomes, whether the incidence of any AEs affected PFS or not was explored among 76 patients. HFS, diarrhea, and rash were significant favorable factors (p = 0.0002, 0.0088, and 0.0011). The median PFS of patients who had all three AEs was 13.2 months, compared with 2.6 months for those who did not (p = 0.00000174). Mucocutaneous toxicities may be predictors of the response to LAP in patients with HER2ABC.

Keywords

HER2-positive advanced breast cancer Lapatinib Mucocutaneous toxicities Predictive marker 

Abbreviations

ABC

Advanced breast cancer

AE

Adverse event

ASCO/CAP

American Society of Clinical Oncology/College of American Pathologists

CBR

Clinical benefit rate

CIs

Confidence intervals

CR

Complete response

EGFR

Epidermal growth factor receptor

ER

Estrogen receptor

HER2

Human epidermal growth factor receptor

HFS

Hand-foot syndrome

IHC

Immunohistochemistry

NCI-CTC-AE

National Cancer Institute Common Terminology Criteria for Adverse Events

NSCLC

Non-small cell lung cancer

ORR

Overall response rate

OS

Overall survival

PFS

Progression-free survival

PR

Partial response

RECIST

Response evaluation criteria in solid tumors

SD

Stable disease

T-DM1

Trastuzumab emtansine

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Notes

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

Takeda Science Foundation to KA.

Supplementary material

10549_2014_3148_MOESM1_ESM.docx (433 kb)
Supplementary material 1 (DOCX 433 kb)

References

  1. 1.
    Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355(26):2733–2743. doi: 10.1056/NEJMoa064320 PubMedCrossRefGoogle Scholar
  2. 2.
    Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K, Group ES (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367 (19):1783–1791. doi: 10.1056/NEJMoa1209124
  3. 3.
    Gelmon KA, Boyle F, Kaufman B, Huntsman D, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Dent SF, Ellard S, Tonkin KS, Nagarwala YM, Pritchard KI, Whelan TJ, Nomikos D, Chapman J-AW, Parulekar W (2012) Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2 + metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919. ASCO Meeting Abstracts 30 (15_suppl):LBA671Google Scholar
  4. 4.
    Goss PE, Smith IE, O’Shaughnessy J, Ejlertsen B, Kaufmann M, Boyle F, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard KI, Lindquist D, Chavarri-Guerra Y, Aktan G, Rappold E, Williams LS, Finkelstein DM, Teach Investigators (2013) Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial. Lancet Oncol 14(1):88–96. doi: 10.1016/S1470-2045(12)70508-9 PubMedCrossRefGoogle Scholar
  5. 5.
    Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Kohne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J, Herceptin Adjuvant Trial Study T (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 382 (9897):1021–1028. doi: 10.1016/S0140-6736(13)61094-6
  6. 6.
    Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J, Breast Cancer International Research G (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365 (14):1273–1283. doi: 10.1056/NEJMoa0910383
  7. 7.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkio S, Flander M, Helle L, Ingalsuo S, Johansson K, Jaaskelainen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J, FinHer Study I (2006) Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 354 (8):809–820. doi: 10.1056/NEJMoa053028
  8. 8.
    Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684. doi: 10.1056/NEJMoa052122 PubMedCrossRefGoogle Scholar
  9. 9.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD, Herceptin Adjuvant Trial Study T (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353 (16):1659–1672. doi: 10.1056/NEJMoa052306
  10. 10.
    Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O’Shaughnessy J (2012) Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol 30(21):2585–2592. doi: 10.1200/JCO.2011.35.6725 PubMedCrossRefGoogle Scholar
  11. 11.
    Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gomez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horvath Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, Neo AST (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379(9816):633–640. doi: 10.1016/S0140-6736(11)61847-3 PubMedCrossRefGoogle Scholar
  12. 12.
    Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical O, College of American P (2014) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 138 (2):241-256. doi: 10.5858/arpa.2013-0953-SA
  13. 13.
    Zardavas D, Cameron D, Krop I, Piccart M (2013) Beyond trastuzumab and lapatinib: new options for HER2-positive breast cancer. Am Soc Clin Oncol Educ Book. doi: 10.1200/EdBook_AM.2013.33.e2
  14. 14.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology/College of American P (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131 (1):18–43. doi: 10.1043/1543-2165(2007)131[18:ASOCCO]2.0.CO;2
  15. 15.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. doi: 10.1016/j.ejca.2008.10.026 PubMedCrossRefGoogle Scholar
  16. 16.
    Paoletti X, Oba K, Bang YJ, Bleiberg H, Boku N, Bouche O, Catalano P, Fuse N, Michiels S, Moehler M, Morita S, Ohashi Y, Ohtsu A, Roth A, Rougier P, Sakamoto J, Sargent D, Sasako M, Shitara K, Thuss-Patience P, Van Cutsem E, Burzykowski T, Buyse M, GASTRIC group (2013) Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: a meta-analysis. J Natl Cancer Inst 105(21):1667–1670. doi: 10.1093/jnci/djt269 PubMedCrossRefGoogle Scholar
  17. 17.
    Yen-Revollo JL, Goldberg RM, McLeod HL (2008) Can inhibiting dihydropyrimidine dehydrogenase limit hand-foot syndrome caused by fluoropyrimidines? Clin Cancer Res 14(1):8–13. doi: 10.1158/1078-0432.CCR-07-1225 PubMedCrossRefGoogle Scholar
  18. 18.
    Coldman AJ, Goldie JH (1987) Impact of dose-intense chemotherapy on the development of permanent drug resistance. Semin Oncol 14(4 Suppl 4):29–33PubMedGoogle Scholar
  19. 19.
    Citron ML (2008) Dose-dense chemotherapy: principles, clinical results and future perspectives. Breast Care (Basel) 3(4):251–255. doi: 10.1159/000148914 CrossRefGoogle Scholar
  20. 20.
    Azim HA Jr, Agbor-Tarh D, Bradbury I, Dinh P, Baselga J, Di Cosimo S, Greger JG Jr, Smith I, Jackisch C, Kim SB, Aktas B, Huang CS, Vuylsteke P, Hsieh RK, Dreosti L, Eidtmann H, Piccart M, de Azambuja E (2013) Pattern of rash, diarrhea, and hepatic toxicities secondary to lapatinib and their association with age and response to neoadjuvant therapy: analysis from the NeoALTTO trial. J Clin Oncol 31(36):4504–4511. doi: 10.1200/JCO.2013.50.9448 PubMedCrossRefGoogle Scholar
  21. 21.
    Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP (2014) Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: american society of clinical oncology clinical practice guideline. J Clin Oncol 32(19):2078–2099. doi: 10.1200/JCO.2013.54.0948 PubMedCrossRefGoogle Scholar
  22. 22.
    Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM, Group CS (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366 (2):109–119. doi: 10.1056/NEJMoa1113216
  23. 23.
    DiGiovanna MP, Stern DF, Edgerton SM, Whalen SG, Moore D 2nd, Thor AD (2005) Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol 23(6):1152–1160. doi: 10.1200/JCO.2005.09.055 PubMedCrossRefGoogle Scholar
  24. 24.
    Cancer Genome Atlas N (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70. doi: 10.1038/nature11412 CrossRefGoogle Scholar
  25. 25.
    Fabi A, Merola R, Ferretti G, Di Benedetto A, Antoniani B, Ercolani C, Nistico C, Papaldo P, Ciccarese M, Sperduti I, Vici P, Marino M, Gori S, Botti C, Malaguti P, Cognetti F, Mottolese M (2013) Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer. Expert Opin Pharmacother 14(6):699–706. doi: 10.1517/14656566.2013.779672 PubMedCrossRefGoogle Scholar
  26. 26.
    Perez-Soler R, Saltz L (2005) Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 23(22):5235–5246. doi: 10.1200/JCO.2005.00.6916 PubMedCrossRefGoogle Scholar
  27. 27.
    Cohen EE, Halpern AB, Kasza K, Kocherginsky M, Williams R, Vokes EE (2009) Factors associated with clinical benefit from epidermal growth factor receptor inhibitors in recurrent and metastatic squamous cell carcinoma of the head and neck. Oral Oncol 45(10):e155–160. doi: 10.1016/j.oraloncology.2009.05.637 PubMedCrossRefGoogle Scholar
  28. 28.
    Wacker B, Nagrani T, Weinberg J, Witt K, Clark G, Cagnoni PJ (2007) Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res 13(13):3913–3921. doi: 10.1158/1078-0432.CCR-06-2610 PubMedCrossRefGoogle Scholar
  29. 29.
    Lee Y, Shim HS, Park MS, Kim JH, Ha SJ, Kim SH, Cho BC (2012) High EGFR gene copy number and skin rash as predictive markers for EGFR tyrosine kinase inhibitors in patients with advanced squamous cell lung carcinoma. Clin Cancer Res 18(6):1760–1768. doi: 10.1158/1078-0432.CCR-11-2582 PubMedCrossRefGoogle Scholar
  30. 30.
    Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M, West Japan Oncology Group (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11(2):121–128. doi: 10.1016/S1470-2045(09)70364-X PubMedCrossRefGoogle Scholar
  31. 31.
    Walko CM, Lindley C (2005) Capecitabine: a review. Clin Ther 27(1):23–44. doi: 10.1016/j.clinthera.2005.01.005 PubMedCrossRefGoogle Scholar
  32. 32.
    Hofheinz RD, Heinemann V, von Weikersthal LF, Laubender RP, Gencer D, Burkholder I, Hochhaus A, Stintzing S (2012) Capecitabine-associated hand-foot-skin reaction is an independent clinical predictor of improved survival in patients with colorectal cancer. Br J Cancer 107(10):1678–1683. doi: 10.1038/bjc.2012.434 PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Jonsson B, Bergh J (2012) Hurdles in anticancer drug development from a regulatory perspective. Nat Rev Clin Oncol 9(4):236–243. doi: 10.1038/nrclinonc.2012.14 PubMedCrossRefGoogle Scholar
  34. 34.
    Sharma MR, Schilsky RL (2012) Role of randomized phase III trials in an era of effective targeted therapies. Nat Rev Clin Oncol 9(4):208–214CrossRefGoogle Scholar
  35. 35.
    Dahabreh IJ, Terasawa T, Castaldi PJ, Trikalinos TA (2011) Systematic review: anti-epidermal growth factor receptor treatment effect modification by KRAS mutations in advanced colorectal cancer. Ann Intern Med 154(1):37–49. doi: 10.7326/0003-4819-154-1-201101040-00006 PubMedCrossRefGoogle Scholar
  36. 36.
    Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139. doi: 10.1056/NEJMoa040938 PubMedCrossRefGoogle Scholar
  37. 37.
    Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B, Goldman J, O’Brien SG, Russell N, Fischer T, Ottmann O, Cony-Makhoul P, Facon T, Stone R, Miller C, Tallman M, Brown R, Schuster M, Loughran T, Gratwohl A, Mandelli F, Saglio G, Lazzarino M, Russo D, Baccarani M, Morra E, International STICMLSG (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346 (9):645–652. doi: 10.1056/NEJMoa011573
  38. 38.
    Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, Group B-S (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364 (26):2507–2516. doi: 10.1056/NEJMoa1103782
  39. 39.
    McLeod HL (2013) Cancer pharmacogenomics: early promise, but concerted effort needed. Science 339(6127):1563–1566. doi: 10.1126/science.1234139 PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Chan EC, New LS, Chua TB, Yap CW, Ho HK, Nelson SD (2012) Interaction of lapatinib with cytochrome P450 3A5. Drug Metab Dispos 40(7):1414–1422. doi: 10.1124/dmd.112.044958 PubMedCrossRefGoogle Scholar
  41. 41.
    Teng WC, Oh JW, New LS, Wahlin MD, Nelson SD, Ho HK, Chan EC (2010) Mechanism-based inactivation of cytochrome P450 3A4 by lapatinib. Mol Pharmacol 78(4):693–703. doi: 10.1124/mol.110.065839 PubMedCrossRefGoogle Scholar
  42. 42.
    Takakusa H, Wahlin MD, Zhao C, Hanson KL, New LS, Chan EC, Nelson SD (2011) Metabolic intermediate complex formation of human cytochrome P450 3A4 by lapatinib. Drug Metab Dispos 39(6):1022–1030. doi: 10.1124/dmd.110.037531 PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Medina PJ, Goodin S (2008) Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther 30(8):1426–1447. doi: 10.1016/j.clinthera.2008.08.008 PubMedCrossRefGoogle Scholar
  44. 44.
    Lamba JK, Lin YS, Thummel K, Daly A, Watkins PB, Strom S, Zhang J, Schuetz EG (2002) Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics 12(2):121–132PubMedCrossRefGoogle Scholar
  45. 45.
    Nakajima M, Fujiki Y, Noda K, Ohtsuka H, Ohkuni H, Kyo S, Inoue M, Kuroiwa Y, Yokoi T (2003) Genetic polymorphisms of CYP2C8 in Japanese population. Drug Metab Dispos 31(6):687–690PubMedCrossRefGoogle Scholar
  46. 46.
    Ando Y, Tateishi T, Sekido Y, Yamamoto T, Satoh T, Hasegawa Y, Kobayashi S, Katsumata Y, Shimokata K, Saito H (1999) Re: modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 91(18):1587–1590. doi: 10.1093/jnci/91.18.1587 PubMedCrossRefGoogle Scholar
  47. 47.
    Roy JN, Lajoie J, Zijenah LS, Barama A, Poirier C, Ward BJ, Roger M (2005) CYP3A5 genetic polymorphisms in different ethnic populations. Drug Metab Dispos 33(7):884–887. doi: 10.1124/dmd.105.003822 PubMedCrossRefGoogle Scholar
  48. 48.
    Fukushima-Uesaka H, Saito Y, Watanabe H, Shiseki K, Saeki M, Nakamura T, Kurose K, Sai K, Komamura K, Ueno K, Kamakura S, Kitakaze M, Hanai S, Nakajima T, Matsumoto K, Saito H, Goto Y, Kimura H, Katoh M, Sugai K, Minami N, Shirao K, Tamura T, Yamamoto N, Minami H, Ohtsu A, Yoshida T, Saijo N, Kitamura Y, Kamatani N, Ozawa S, Sawada J (2004) Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population. Hum Mutat 23(1):100. doi: 10.1002/humu.9210 PubMedCrossRefGoogle Scholar
  49. 49.
    Floyd MD, Gervasini G, Masica AL, Mayo G, George AL Jr, Bhat K, Kim RB, Wilkinson GR (2003) Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women. Pharmacogenetics 13(10):595–606. doi: 10.1097/01.fpc.0000054118.14659.48 PubMedCrossRefGoogle Scholar
  50. 50.
    Yamamoto N, Murakami H, Hayashi H, Fujisaka Y, Hirashima T, Takeda K, Satouchi M, Miyoshi K, Akinaga S, Takahashi T, Nakagawa K (2013) CYP2C19 genotype-based phase I studies of a c-Met inhibitor tivantinib in combination with erlotinib, in advanced/metastatic non-small cell lung cancer. Br J Cancer 109(11):2803–2809. doi: 10.1038/bjc.2013.588 PubMedCrossRefGoogle Scholar
  51. 51.
    Yamamoto N, Murakami H, Nishina T, Hirashima T, Sugio K, Muro K, Takahashi T, Naito T, Yasui H, Akinaga S, Koh Y, Boku N (2013) The effect of CYP2C19 polymorphism on the safety, tolerability, and pharmacokinetics of tivantinib (ARQ 197): results from a phase I trial in advanced solid tumors. Ann Oncol 24(6):1653–1659. doi: 10.1093/annonc/mdt014 PubMedCrossRefGoogle Scholar
  52. 52.
    Yap TA, Olmos D, Brunetto AT, Tunariu N, Barriuso J, Riisnaes R, Pope L, Clark J, Futreal A, Germuska M, Collins D, deSouza NM, Leach MO, Savage RE, Waghorne C, Chai F, Garmey E, Schwartz B, Kaye SB, de Bono JS (2011) Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies. J Clin Oncol 29(10):1271–1279. doi: 10.1200/JCO.2010.31.0367 PubMedCrossRefGoogle Scholar
  53. 53.
    Tannock IF (2009) Effects of food on bioavailability of lapatinib: useful data, wrong conclusion. J Clin Oncol 27 (22):e42; author reply e43. doi: 10.1200/JCO.2009.23.8899
  54. 54.
    Koch KM, Reddy NJ, Cohen RB, Lewis NL, Whitehead B, Mackay K, Stead A, Beelen AP, Lewis LD (2009) Effects of food on the relative bioavailability of lapatinib in cancer patients. J Clin Oncol 27(8):1191–1196. doi: 10.1200/JCO.2008.18.3285 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kazuhiro Araki
    • 1
  • Ippei Fukada
    • 1
  • Rie Horii
    • 4
    • 5
  • Shunji Takahashi
    • 3
  • Futoshi Akiyama
    • 4
    • 5
  • Takuji Iwase
    • 2
  • Yoshinori Ito
    • 1
  1. 1.Beast Medical Oncology, Breast Oncology CenterThe Cancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  2. 2.Breast Surgical Oncology, Breast Oncology CenterThe Cancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  3. 3.Medical OncologyThe Cancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  4. 4.The Cancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  5. 5.Division of PathologyThe Cancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan

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