Dasatinib plus capecitabine for advanced breast cancer: Safety and efficacy in phase I study CA180004

Clinical Cancer Research

Volumn 19, Issue 7, 2013, Pages 1884-1893

  Somlo, George ^a   Atzori, Francesco ^b   Strauss, Lewis C ^c   Geese, William J ^c   Specht, Jennifer M ^d   Gradishar, William J ^e   Rybicki, Alissa ^c   Sy, Oumar ^c   Vahdat, Linda T ^f   Cortes, Javier ^g  

^a CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^b DEPARTMENT OF RADIOLOGY   (Italy)

^c BRISTOL MYERS SQUIBB   (United States)

^d UNIVERSITY OF WASHINGTON   (United States)

^e NORTHWESTERN UNIVERSITY   (United States)

^f WEILL CORNELL MEDICAL COLLEGE   (United States)

^g HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; CAPECITABINE; COLLAGEN TYPE 4; DASATINIB; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 2;

ADULT; AGED; ARTICLE; ASTHENIA; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; COUGHING; DECREASED APPETITE; DIARRHEA; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG SAFETY; DRUG WITHDRAWAL; DYSGEUSIA; DYSPNEA; FATIGUE; FEMALE; FEVER; HAND FOOT SYNDROME; HEADACHE; HUMAN; HYPOKALEMIA; MAJOR CLINICAL STUDY; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; PAIN; PATIENT COMPLIANCE; PHASE 1 CLINICAL TRIAL; PLEURA EFFUSION; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; UNSPECIFIED SIDE EFFECT; VOMITING;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BIOLOGICAL MARKERS; BREAST NEOPLASMS; DEOXYCYTIDINE; FEMALE; FLUOROURACIL; HUMANS; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASM STAGING; PYRIMIDINES; THIAZOLES; TREATMENT OUTCOME;

EID: 84877088758     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-12-0652     Document Type: Article

References (51)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
2. Kiely BE, Soon YY, Tattersall MH, Stockler MR. How long have I got? Estimating typical, best-case, and worst-case scenarios for patients starting first-line chemotherapy for metastatic breast cancer: a systematic review of recent randomized trials. J Clin Oncol 2011;29:456-63.
3. Carlson RW, Allred DC, Anderson BO, Burstein HJ, Edge SB, Farrar WB, et al. Metastatic breast cancer. Version 1.2012: Featured Updates to the NCCN Guidelines. J Natl Compr Canc Netw 2012;10:821-9.
4. Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, et al. Combination of anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med 2012;367:435-44.
5. Baselga J, Cortes J, Kim SB, IM SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366:109-19.
6. Aleshin A, Finn RS. SRC: a century of science brought to the clinic. Neoplasia 2010;8:599-607.
7. Mayer EL, Krop IE. Advances in targeting src in the treatment of breast cancer and other solid malignancies. Clin Cancer Res 2010;16:3526-32.
8. Myoui A, Nishimura R, Williams PJ, Hiraga T, Tamura D, Michigami T, et al. C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. Cancer Res 2003;63:5028-33. (Pubitemid 37022641)
9. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 2009;16:67-78.
10. Vultur A, Buettner R, Kowolik C, Liang W, Smith D, Boschelli F, et al. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Mol Cancer Ther 2008;7:1185-94.
11. Elsberger B, Fullerton R, Zino S, Jordan F, Mitchell TJ, Brunton VG, et al. Breast cancer patients' clinical outcome measures are associated with Src kinase family member expression. Br J Cancer 2010;103:899-909.
12. Biscardi JS, Belsches AP, Parsons SJ. Characterization of human epidermal growth factor receptor and c-Src interactions in human breast tumor cells. Mol Carcinogen 1998;21:261-72. (Pubitemid 28208747)
13. Belsches-Jablonski AP, Biscardi JS, Peavy DR, Tice DA, Romney DA, Parsons SJ. Src family kinases and HER2 interactions in human breast cancer cell growth and survival. Oncogene 2001;20:1465-75. (Pubitemid 32291197)
14. Song RX, Zhang Z, Santen RJ. Estrogen rapid action via protein complex formation involving ERalpha and Src. Trends Endocrinol Metab 2005;16:347-53. (Pubitemid 41338739)
15. Planas-Silva MD, Bruggeman RD, Grenko RT, Stanley SJ. Role of c-Src and focal adhesion kinase in progression and metastasis of estrogen receptor-positive breast cancer. Biochem Biophys Res Commun 2006;341:73-81. (Pubitemid 43118368)
16. Hiscox S, Jordan NJ, Smith C, James M, Morgan L, Taylor KM, et al. Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells. Breast Cancer Res Treat 2009;115:57-67.
17. Herynk MH, Beyer AR, Cui Y, Weiss H, Anderson E, Green TP, et al. Cooperative action of tamoxifen and c-Src inhibition in preventing the growth of estrogen receptor-positive human breast cancer cells. Mol Cancer Ther 2006;5:3023-31. (Pubitemid 46092043)
18. Rexer BN, Ham A-JL, Rinehart C, Hill S, de Matos Granja-Ingram N, Gonzalez-Angulo AM, et al. Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition. Oncogene 2011;30:4163-74.
19. Mukhopadhyay D, Datta K. Multiple regulatory pathways of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in tumors. Semin Cancer Biol 2004;14:123-30. (Pubitemid 38234754)
20. Gray MJ, Zhang J, Ellis LM, Semenza GL, Evans DB, Watowich SS, et al. HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncogene 2005;24:3110-20. (Pubitemid 40695080)
21. Laird AD, Li G, Moss KG, Blake RA, Broome MA, Cherrington JM, et al. Src family kinase activity is required for signal transducer and activator of transcription 3 and focal adhesion kinase phosphorylation and vascular endothelial growth factor signaling in vivo and for anchorage-dependent and -independent growth of human tumor cells. Mol Cancer Ther 2003;2:461-9.
22. Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K, et al. Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1- yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 2004;47:6658-61. (Pubitemid 40053752)
23. Araujo J, Logothetis C. Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors. Cancer Treat Rev 2010;36:492-500.
24. Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N, et al. Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/''triple-negative' breast cancer cell lines growing in vitro. Breast Cancer Res Treat 2007;105:319-26. (Pubitemid 47596452)
25. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121:2750-67.
26. Vandyke K, Dewar AL, Diamond P, Fitter S, Schultz CG, Sims NA, et al. The tyrosine kinase inhibitor dasatinib dysregulates bone remodelling through inhibition of osteoclasts in vivo . J Bone Miner Res 2010;25:1759-70.
27. Nautiyal J, Majumder P, Patel BB, Lee FY, Majumdar AP. Src inhibitor dasatinib inhibits growth of breast cancer cells by modulating EGFR signaling. Cancer Lett 2009;283:143-51.
28. Choi YL, Bocanegra M, Kwon MJ, Shin YK, Nam SJ, Yang JH, et al. LYN is a mediator of epithelial-mesenchymal transition and a target of dasatinib in breast cancer. Cancer Res 2010;70:2296-306.
29. Finn RS, Bengala C, Ibrahim N, Roché H, Sparano J, Strauss LC, et al. Dasatinib as a single agent in triple-negative breast cancer: results of an open-label phase 2 study. Clin Cancer Res 2011;17:6905-13.
30. Mayer E, Baurain J-F, Sparano J, Strauss L, Campone M, Fumoleau P, et al. Dasatinib in advanced HER2/neu amplified and ER/PR-positive breast cancer: phase II study CA180088. J Clin Oncol 27:43s, 2009(suppl; abstr 1011).
31. Strauss LC, Sy O, Fairchild J, Fu C, Rybicki A, Yoganathan S, et al. Biomarker analyses in phase 2 single-agent trials of dasatinib for breast cancer. Cancer Res 2009;69(suppl):603s. Abstract nr 2034.
32. Shah NP, Kantarjian HM, Kim DW, Réa D, Dorlhiac-Llacer PE, Milone JH, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 2008;26:3204-12.
33. Yu EY, Massard C, Gross ME, Carducci MA, Culine S, Hudes G, et al. Once-daily dasatinib: expansion of phase II study evaluating safety and efficacy of dasatinib in patients with metastatic castration-resistant prostate cancer. Urology 2011;77:1166-71.
34. Bonett DG, Price RM. Statistical inference for a linear function of medians: confidence intervals, hypothesis testing, and sample size requirements. Psychol Methods 2002;7:370-83.
35. Leonard R, Hennessy BT, Blum JL, O'Shaughnessy J. Dose-adjusting capecitabine minimizes adverse effects while maintaining efficacy: a retrospective review of capecitabine for metastatic breast cancer. Clin Breast Cancer 2011;11:349-56.
36. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005;23:792-9. (Pubitemid 46224178)
37. Sparano JA, Vrdoljak E, Rix O, Xu B, Manikhas A, Medina C, et al. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2010;28:3256-63.
38. Fornier MN, Morris PG, Abbruzzi A, D'Andrea G, Gilewski T, Bromberg J, et al.Aphase I study of dasatinib and weekly paclitaxel for metastatic breast cancer. Ann Oncol 2011;22:2575-81.
39. Schwartzberg LS, Blakely LJ, Schnell F, Christianson D, Andrews M, Johns A, et al. Phase I/II trial of ixabepilone (Ixa) and dasatinib (D) for treatment of metastatic breast cancer (MBC). In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011; Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; 2011. Abstract nr 4714.
40. Wright GL, Blum J, Krekow LK, McIntyre KJ, Wilks ST, Rabe AC, et al. Randomized phase II trial of fulvestrant with or without dasatinib in postmenopausal patients with hormone receptor-positive metastatic breast cancer previously treated with an aromatase inhibitor. Cancer Res 2011;71(24 Suppl):116s. Abstract nr PD01-01.
41. Llombart A, Ravaioli A, Strauss L, Sy O, Abrahao F, Geese WJ, et al. Randomized Phase II study of dasatinib vs placebo in addition to exemestane in advanced ER/PR-positive breast cancer: BMS study CA180261. Cancer Res 2011;71(24 Suppl):117s. Abstract nr PD01-02.
42. Strauss LC, O'Shaughnessy J, Jackson J, Paul D, Wright DL, Rybicki A, et al. Three parallel randomized phase II trials of dasatinib plus hormone therapy (HT) in advanced ER+ breast cancer (ER+ ABC). J Clin Oncol 28:15s, 2010 (suppl; abstr TPS133).
43. Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009;6:327-38.
44. Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 1995;375:577-81.
45. Eliceiri BP, Paul R, Schwartzberg PL,Hood JD, Leng J, Cheresh DA. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Molecular Cell 1999;l4:915-24.
46. Park SI, Shah AN, Zhang J, Gallick GE. Regulation of angiogenesis and vascular permeability by Src family kinases: opportunities for therapeutic treatment of solid tumors. Expert Opin Ther Targets 2007;11:1207-17. (Pubitemid 47527325)
47. Pham N-A, Magalhaes JMMM, Do T, Schwock J, Dhani N, Cao P-J, et al. Activation of Src and Src-associated signaling pathways in relation to hypoxia in human cancer xenograft models. Int J Cancer 2009;124:280-6.
48. Denduluri N, Yang SX, Berman AW, Nguyen D, Liewehr DJ, Steinberg SM, et al. Circulating biomarkers of bevacizumab activity in patients with breast cancer. Cancer Biol Ther 2008;7:15-20. (Pubitemid 351590445)
49. Deprimo SE, Bello CL, Smeraglia J, Baum CM, Spinella D, Rini BI, et al. Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med 2007;5:32.
50. Norden-Zfoni A, Desai J, Manola J, Beaudry P, Force J, Maki R, et al. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res 2007;13:2643-50. (Pubitemid 46788031)
51. Murukesh N, Dive C, Jayson GC. Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Brit J Cancer 2010;102:8-18.