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Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors
Open accessPublished version of a preprint
Abstract
Purpose: To determine the maximum tolerated dose, dose-limiting toxicity (DLT), and recommended phase II dose of dasatinib in metastatic solid tumors refractory to standard therapies or for which no effective standard therapy exists. Experimental Design: In this phase I, open-label, dose-escalation study, patients received 35 to 160 mg of dasatinib twice daily in 28-day cycles either every 12 hours for 5 consecutive days followed by 2 nontreatment days every week (5D2) or as continuous, twice-daily (CDD) dosing. Results: Sixty-seven patients were treated (5D2, n = 33; CDD, n = 34). The maximum tolerated doses were 120 mg twice daily 5D2 and 70 mg twice daily CDD. DLTs with 160 mg 5D2 were recurrent grade 2 rash, grade 3 lethargy, and one patient with both grade 3 prolonged bleeding time and grade 3 hypocalcemia; DLTs with 120 mg twice daily CDD were grade 3 nausea, grade 3 fatigue, and one patient with both grade 3 rash and grade 2 proteinuria. The most frequent treatment-related toxicities across all doses were nausea, fatigue, lethargy, anorexia, proteinuria, and diarrhea, with infrequent hematologic toxicities. Pharmacokinetic data indicated rapid absorption, dose proportionality, and lack of drug accumulation. Although no objective tumor responses were seen, durable stable disease was observed in 16% of patients. Conclusion: Dasatinib was well tolerated in this population, with a safety profile similar to that observed previously in leukemia patients, although with much less hematologic toxicity. Limited, although encouraging, preliminary evidence of clinical activity was observed. Doses of 120 mg twice daily (5D2) or 70 mg twice daily (CDD) are recommended for further studies in patients with solid tumors. (Clin Cancer Res 2009;15(19):6232–40)
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“To date, Src inhibitors as monotherapy have not yielded promising results [46, 47].”
From Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src (2016) · cites this paper as [46]
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Cites
CELLULAR FUNCTIONS REGULATED BY SRC FAMILY KINASES
Thomas, S. Μ., & Brugge, J. S. (1997) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.13.1.513 · Cited by 2,537
Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice
Soriano, P. M., Montgomery, C. A., Geske, R. S., & Bradley, A. (1991) · Cell · doi:10.1016/0092-8674(91)90499-o · Cited by 1,997
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias
Talpaz, M., Shah, N. P., Kantarjian, H., Donato, N., Nicoll, J., Paquette, R., Cortes, J., O'Brien, S., Nicaise, C., Bleickardt, E., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055229 · Cited by 1,760
Young, H. E., Baum, R. P., Cremerius, U., Herholz, K., Hoekstra, O. S., Lammertsma, A. A., Pruim, J., & Price, P. (1999) · European Journal of Cancer · doi:10.1016/s0959-8049(99)00229-4 · Cited by 1,740
Lombardo, L. J., Lee, F. Y., Chen, P., Norris, D. J., Barrish, J. C., Behnia, K., Castaneda, S., Cornelius, L. A. M., Das, J., Doweyko, A. M., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049486a · Cited by 1,303
Src family kinases in tumor progression and metastasis
Summy, J. M., & Gallick, G. E. (2003) · Cancer and Metastasis Reviews · doi:10.1023/a:1023772912750 · Cited by 827
Hochhaus, A., Kantarjian, H. M., Baccarani, M., Lipton, J. H., Apperley, J. F., Druker, B. J., Facon, T. T. F., Goldberg, S. L., Cervantes, F., Niederwieser, D. W., et al. (2006) · Blood · doi:10.1182/blood-2006-09-047266 · Cited by 603
Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice.
Boyce, B. F., Yoneda, T., Lowe, C., Soriano, P. M., & Mundy, G. R. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116032 · Cited by 553
Miao, H., Burnett, E., Kinch, M. S., Simon, E., & Wang, B.-C. (1999) · Nature Cell Biology · doi:10.1038/35000008 · Cited by 547
Shah, N. P., Kantarjian, H. M., Kim, D., Réa, D., Dorlhiac‐Llacer, P. E., Milone, J. H., Vela‐Ojeda, J., Silver, R. T., Khoury, H. J., Charbonnier, A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.9260 · Cited by 483
Schittenhelm, M. M., Shiraga, S., Schroeder, A., Corbin, A. S., Griffith, D., Lee, F. Y., Bokemeyer, C., Deininger, M. W., Druker, B. J., & Heinrich, M. C. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2050 · Cited by 468
Cortes, J. E., Rousselot, P. H., Kim, D., Ritchie, E. K., Hamerschlak, N., Coutre, S. E., Hochhaus, A., Guilhot, F., Saglio, G. N., Apperley, J. F., et al. (2006) · Blood · doi:10.1182/blood-2006-09-046888 · Cited by 409
Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer.
Talamonti, M. S., Roh, M. S., Curley, S. A., & Gallick, G. E. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116200 · Cited by 399
Quintás‐Cardama, A., Kantarjian, H. M., O'Brien, S. M., Borthakur, G., Bruzzi, J. F., Munden, R. F., & Cortes, J. E. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.0329 · Cited by 392
Sanjay, A., Houghton, A., Neff, L., DiDomenico, E., Bardelay, C., Antoine, E., Levy, J. B., Gailit, J. O., Bowtell, D. D. L., Horne, W. C., et al. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.1.181 · Cited by 371
Ottmann, O. G., Dombret, H., Martinelli, G., Simonsson, B., Guilhot, F., Larson, R. A., Rege‐Cambrin, G., Radich, J. P., Hochhaus, A., Apanovitch, A. M., et al. (2007) · Blood · doi:10.1182/blood-2007-02-073528 · Cited by 367
Guilhot, F., Apperley, J. F., Kim, D., Bullorsky, E. O., Baccarani, M., Roboz, G. J., Amadori, S., Souza, C. A. D., Lipton, J. H., Hochhaus, A., et al. (2007) · Blood · doi:10.1182/blood-2006-09-046839 · Cited by 365
Role of B61, the Ligand for the Eck Receptor Tyrosine Kinase, in TNF-α-Induced Angiogenesis
Pandey, A., Shao, H., Marks, R. M., Polverini, P. J., & Dixit, V. M. (1995) · Science · doi:10.1126/science.7536959 · Cited by 363
Tsukita, S., Oishi, K., Akiyama, T. H., Yamanashi, Y., Yamamoto, T. S., & Tsukita, S. (1991) · The Journal of Cell Biology · doi:10.1083/jcb.113.4.867 · Cited by 308
Ottenhoff-Kalff, A. E., Rijksen, G., van Beurden, E. A., Hennipman, A. H., Michels, A. A., & Staal, G. E. J. (1992) · PubMed · Cited by 306
Activation of pp60c-src protein kinase activity in human colon carcinoma.
Bolen, J. B., Veillette, A., Schwartz, A. M., DeSeau, V, & Rosen, N. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.8.2251 · Cited by 299
Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis.
Cartwright, C. A., Meisler, A. I., & Eckhart, W. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.2.558 · Cited by 277
Verbeek, B. S., Feltkamp‐Vroom, T. M., Adriaansen-slot, S. S., Ottenhoff-Kalff, A. E., GEERTZEMA, J. G. N., Hennipman, A., & Rijksen, G. (1996) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199612)180:4 · Cited by 268
Tyrosine Phosphorylation and Src Family Kinases Control Keratinocyte Cell–Cell Adhesion
Calautti, E., Cabodi, S., Stein, P., Hatzfeld, M., Kedersha, N., & Dotto, G. P. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.6.1449 · Cited by 261
Overexpression and Activation of the Tyrosine Kinase Src in Human Pancreatic Carcinoma
Lutz, M. P., Eßer, I. B. S., Flossmann-Kast, B. B. M., Vogelmann, R., Lührs, H., Friess, H., Büchler, M. W., & Adler, G. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.8043 · Cited by 248
Trevino, J. G., Summy, J. M., Lesslie, D. P., Parikh, N. U., Hong, D. S., Lee, F. Y., Donato, N. J., Abbruzzese, J. L., Baker, C. H., & Gallick, G. E. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050570 · Cited by 206
Metabolism and disposition of dasatinib after oral administration to humans
Christopher, L. J., Cui, D., Wu, C., Luo, R., Manning, J. A., Bonacorsi, S. J., Lago, M., Allentoff, A., Lee, F. Y. F., McCann, B., et al. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.018267 · Cited by 202
Involvement of platelet-derived growth factor in disease: development of specific antagonists
Östman, A., & Heldin, C. (2001) · Advances in cancer research · doi:10.1016/s0065-230x(01)80010-5 · Cited by 200
Lung Abnormalities after Dasatinib Treatment for Chronic Myeloid Leukemia
Bergeron, A., Réa, D., Lévy, V., Picard, C., Meignin, V., Tamburini, J., Bruzzoni‐Giovanelli, H., Calvo, F. M., Tazi, A., & Rousselot, P. H. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200705-715cr · Cited by 183
Targeting mutations in solid tumors: Scientific rationale and novel therapeutic options
Demetri, G. D. (2001) · Seminars in Oncology · doi:10.1016/s0093-7754(01)90099-5 · Cited by 168
Self-citationProfound Inhibition of Antigen-Specific T-Cell Effector Functions by Dasatinib
Weichsel, R., Dix, C., Wooldridge, L., Clement, M., Fenton-May, A. E., Sewell, A. K., Zezula, J., Greiner, E., Emma Gostick, D., Price, D. A., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4393 · Cited by 137
Andres, A. C., Reid, H. H., Zürcher, G., Blaschke, R. J., Albrecht, D., & Ziemiecki, A. (1994) · PubMed · Cited by 126
Src Family Kinases: Potential Targets for the Treatment of Human Cancer and Leukemia
Warmuth, M., Damoiseaux, R. D., Liu, Y., Fabbro, D., & Gray, N. S. (2003) · Current Pharmaceutical Design · doi:10.2174/1381612033454126 · Cited by 111
Role of c-kit/SCF in cause and treatment of gastrointestinal stromal tumors (GIST)
Ali, S., & Ali, S. (2007) · Gene · doi:10.1016/j.gene.2007.06.017 · Cited by 91
Src activation in malignant and premalignant epithelia of Barrett's esophagus
Kumble, S., Omary, M. B., Cartwright, C., & Triadafilopoulos, G. (1997) · Gastroenterology · doi:10.1053/gast.1997.v112.pm9024288 · Cited by 72
Contemporary Pathology of Gastrointestinal Stromal Tumors
Liegl, B., Hornick, J. L., & Lazar, A. J. (2009) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2008.12.002 · Cited by 46
Src Inhibitors in Metastatic Bone Disease
Boyce, B. F., Xing, L., Yao, Z., Yamashita, T., Shakespeare, W. C., Wang, Y., Metcalf, C. A., Sundaramoorthi, R., Dalgarno, D. C., Iuliucci, J. D., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0991 · Cited by 43
pp60c‐src protein kinase activity in human gastric carcinomas
Takekura, N., Yasui, W., Yoshida, K., Tsujino, T., Nakayama, H., Kameda, T., Yokozaki, H., Ishimura, Y., Ito, H., & Tahara, E. (1990) · International Journal of Cancer · doi:10.1002/ijc.2910450510 · Cited by 34
Freebern, W. J., Fang, H. S., Slade, M. D., Wells, S., Canale, J., Megill, J. R., Grubor, B., Shi, H., Fletcher, A. M., Lombardo, L. J., et al. (2007) · Blood · doi:10.1182/blood.v110.11.4582.4582 · Cited by 28
Luo, F. R., Luo, F. R., Barrett, Y., Ji, P., Holly, P., McCann, E. J., Rhyne, P., Clarke, E., He, K., Bleichardt, E., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.3046 · Cited by 16
Lee, F. Y., Lombardo, L. J., Borzilleri, R. M., Camuso, A., Castaneda, S., Donato, N. J., Fager, K., Flefleh, C., Gray, H., Inigo, I. V., et al. (2004) · Cancer Research · Cited by 5
Lesslie, D. P., Parikh, N. U., Shah, A. N., Summy, J. M., Trevino, J. G., Hong, D. S., Donato, N. J., Lee, F. Y., & Gallick, G. E. (2006) · Cancer Research · Cited by 5
Research works printed but not linked: 2
- Lee, 2004, BMS-354825—a potent dual SRC/ABL kinase inhibitor possessing curative efficacy against imatinib sensitive and resistant human CML models in vivo [abstract 3987], Proc Am Assoc Cancer Res, 45 Suppl, 92
- WHO, 1979, World Health Organization handbook for reporting results for cancer treatment
Cited by
Sorted by citations
Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology
Gradishar, W. J., Anderson, B. O., Balassanian, R., Blair, S. L., Burstein, H. J., Cyr, A. E., ELIAS, A. D., Farrar, W. B., Forero, A., Giordano, S. H., et al. (2018) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2018.0012 · Cited by 1,612
NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors
Demetri, G. D., von Mehren, M., Antonescu, C. R., DeMatteo, R. P., Ganjoo, K. N., Maki, R. G., Pisters, P. W. T., Raut, C. P., Riedel, R. F., Schuetze, S. M., et al. (2010) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2010.0116 · Cited by 1,215
Self-citationDasatinib: A potent SRC inhibitor in clinical development for the treatment of solid tumors
Araujo, J., & Logothetis, C. (2010) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2010.02.015 · Cited by 244
Pharmacologic control of CAR-T cell function using dasatinib
Weber, E. W., Lynn, R. C., Sotillo, E., Lattin, J., Xu, P., & Mackall, C. L. (2019) · Blood Advances · doi:10.1182/bloodadvances.2018028720 · Cited by 246
Clinical Pharmacokinetics of Tyrosine Kinase Inhibitors
Gion, P. D., Kanefendt, F., Lindauer, A., Scheffler, M., Doroshyenko, O., Fuhr, U., Wolf, J., & Jaehde, U. (2011) · Clinical Pharmacokinetics · doi:10.2165/11593320-000000000-00000 · Cited by 224
Metadata
- Authors
- Demetri, G. D., Lo Russo, P., MacPherson, I. R. J., Wang, D., Morgan, J. A., Brunton, V. G., Paliwal, P., Agrawal, S., Voi, M., & Evans, T. R. J.
- Affiliations
- Harvard University (US)
- Authors' Affiliations: 1Ludwig Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; 2Karmanos Cancer Institute, Detroit, Michigan; 3Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; 4University of Edinburgh, Edinburgh, United Kingdom; and 5Bristol-Myers Squibb, Wallingford, Connecticut
- Corresponding author
- Demetri, George D.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2009-09-30
- Volume
- 15
- Issue
- 19
- Pages
- 6232-6240
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2143060756
- Cited by
- 150
- References
- 42
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 12 · 2020: 13 · 2019: 11 · 2018: 7 · 2017: 3 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 15 · 2012: 7
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- dasatinib, advanced solid tumors, metastatic solid tumors, maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, dosing regimen, hematologic toxicity, proteinuria, tyrosine kinase inhibitors
- MeSH terms
- Dasatinib, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Neoplasms, Pyrimidines, Thiazoles, Treatment Outcome, Drug Resistance, Neoplasm, Maximum Tolerated Dose
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