Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes

British Journal of Haematology

Volumn 162, Issue 4, 2013, Pages 517-524

  Komrokji, Rami S ^a   Raza, Azra ^b   Lancet, Jeffrey E ^a   Ren, Chen ^c   Taft, David ^d   Maniar, Manoj ^c   Wilhelm, Francois ^c   List, Alan F ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b NewYork Presbyterian Hospital   (United States)

^c Onconova Therapeutics Inc   (United States)

^d LONG ISLAND UNIVERSITY   (United States)

Author keywords

Myelodysplastic syndromes; Phosphoinositide 3 kinase; Polo like kinase; Rigosertib

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; AZACITIDINE; ON 01910NA; RIGOSERTIB; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; AGED; ANOREXIA; ARTICLE; CLINICAL ARTICLE; COHORT ANALYSIS; CYSTITIS; DIARRHEA; DOSE RESPONSE; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG FORMULATION; DRUG HALF LIFE; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; DYSURIA; FAINTNESS; FATIGUE; FEMALE; FOOD; FOOD DRUG INTERACTION; HEMATURIA; HUMAN; HYPOTENSION; MALE; MAXIMUM TOLERATED DOSE; MYELODYSPLASTIC SYNDROME; NOCTURIA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REFRACTORY ANEMIA WITH EXCESS BLASTS; REFRACTORY CYTOPENIA WITH MULTILINEAGE DYSPLASIA; REMISSION; SIDE EFFECT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT DURATION; URINARY FREQUENCY; URINARY TRACT INFLAMMATION; UROTHELIAL INFLAMMATION;

MYELODYSPLASTIC SYNDROMES; PHOSPHOINOSITIDE-3-KINASE; POLO-LIKE KINASE; RIGOSERTIB;

ADMINISTRATION, ORAL; AGED; AGED, 80 AND OVER; BIOLOGICAL AVAILABILITY; CAPSULES; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; DYSPNEA; FEMALE; FOOD-DRUG INTERACTIONS; GASTROINTESTINAL DISEASES; GLYCINE; HUMANS; MALE; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; PROTEIN KINASE INHIBITORS; REMISSION INDUCTION; SULFONES; TREATMENT OUTCOME; UROLOGIC DISEASES;

EID: 84880686104     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12436     Document Type: Article

References (26)

1. Chapman, C.M., Sun, X., Roschewski, M., Aue, G., Farooqui, M., Stennett, L., Gibellini, F., Arthur, D., Perez-Galan, P. & Wiestner, A. (2012) ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clinical Cancer Research, 18, 1979-1991.
2. Cheson, B.D., Bennett, J.M., Kantarjian, H., Pinto, A., Schiffer, C.A., Nimer, S.D., Lowenberg, B., Beran, M., de Witte, T.M., Stone, R.M., Mittelman, M., Sanz, G.F., Wijermans, P.W., Gore, S. & Greenberg, P.L. (2000) Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood, 96, 3671-3674.
3. Cheson, B.D., Greenberg, P.L., Bennett, J.M., Lowenberg, B., Wijermans, P.W., Nimer, S.D., Pinto, A., Beran, M., de Witte, T.M., Stone, R.M., Mittelman, M., Sanz, G.F., Gore, S.D., Schiffer, C.A. & Kantarjian, H. (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood, 108, 419-425.
4. Fenaux, P. (2004) Myelodysplastic syndromes: from pathogenesis and prognosis to treatment. Seminars in Hematology, 41, 6-12.
5. Fenaux, P., Mufti, G.J., Hellstrom-Lindberg, E., Santini, V., Finelli, C., Giagounidis, A., Schoch, R., Gattermann, N., Sanz, G., List, A., Gore, S.D., Seymour, J.F., Bennett, J.M., Byrd, J., Backstrom, J., Zimmerman, L., McKenzie, D., Beach, C. & Silverman, L.R. (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. The Lancet Oncology, 10, 223-232.
6. Greenberg, P., Cox, C., Le Beau, M.M., Fenaux, P., Morel, P., Sanz, G., Sanz, M., Vallespi, T., Hamblin, T., Oscier, D., Ohyashiki, K., Toyama, K., Aul, C., Mufti, G. & Bennett, J. (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood, 89, 2079-2088.
7. Greenberg, P.L., Attar, E., Bennett, J.M., Bloomfield, C.D., De Castro, C.M., Deeg, H.J., Foran, J.M., Gaensler, K., Garcia-Manero, G., Gore, S.D., Head, D., Komrokji, R., Maness, L.J., Millenson, M., Nimer, S.D., O'Donnell, M.R., Schroeder, M.A., Shami, P.J., Stone, R.M., Thompson, J.E. & Westervelt, P. (2011) NCCN Clinical Practice Guidelines in Oncology: myelodysplastic syndromes. Journal of the National Comprehensive Cancer Network: JNCCN, 9, 30-56.
8. Greenberg, P.L., Tuechler, H., Schanz, J., Sanz, G., Garcia-Manero, G., Sole, F., Bennett, J.M., Bowen, D., Fenaux, P., Dreyfus, F., Kantarjian, H., Kuendgen, A., Levis, A., Malcovati, L., Cazzola, M., Cermak, J., Fonatsch, C., Le Beau, M.M., Slovak, M.L., Krieger, O., Luebbert, M., Maciejewski, J., Magalhaes, S.M., Miyazaki, Y., Pfeilstocker, M., Sekeres, M., Sperr, W.R., Stauder, R., Tauro, S., Valent, P., Vallespi, T., van de Loosdrecht, A.A., Germing, U. & Haase, D. (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood, 120, 2454-2465.
9. Gumireddy, K., Reddy, M.V., Cosenza, S.C., Boominathan, R., Baker, S.J., Papathi, N., Jiang, J., Holland, J. & Reddy, E.P. (2005) ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell, 7, 275-286.
10. Harris, N.L., Jaffe, E.S., Diebold, J., Flandrin, G., Muller-Hermelink, H.K., Vardiman, J., Lister, T.A. & Bloomfield, C.D. (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. Journal of Clinical Oncology, 17, 3835-3849.
11. Jabbour, E., Garcia-Manero, G., Batty, N., Shan, J., O'Brien, S., Cortes, J., Ravandi, F., Issa, J.P. & Kantarjian, H. (2010) Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer, 116, 3830-3834.
12. Jimeno, A., Li, J., Messersmith, W.A., Laheru, D., Rudek, M.A., Maniar, M., Hidalgo, M., Baker, S.D. & Donehower, R.C. (2008) Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. Journal of Clinical Oncology, 26, 5504-5510.
13. Kantarjian, H.M., O'Brien, S., Shan, J., Aribi, A., Garcia-Manero, G., Jabbour, E., Ravandi, F., Cortes, J., Davisson, J. & Issa, J.P. (2007) Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome. Cancer, 109, 265-273.
14. Kaplan, E.L. & Meier, P. (1958) Nonparametric estimation from incomplete observations. Journal of the American Statistical Association, 53, 457-481.
15. Komrokji, R.S., Sekeres, M.A. & List, A.F. (2011) Management of lower-risk myelodysplastic syndromes: the art and evidence. Current Hematologic Malignancy Reports, 6, 145-153.
16. Li, J., Zhao, M., Jimeno, A., He, P., Ramana Reddy, M.V., Hidalgo, M., Donehower, R.C. & Rudek, M.A. (2007) Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate ON 01910.Na, a mitotic progression modulator, in human plasma. Journal of Chromatography B, 856, 198-204.
17. Lin, K., Reljic, T., Kumar, A., Lancet, J.E., List, A.F. & Komrokji, R.S. (2010) Poor outcome of patients with myelodysplastic syndrome (MDS) after azacitidine treatment failure. Blood (ASH Annual Meeting Abstracts), 116, 2913.
18. Olnes, M.J., Shenoy, A., Weinstein, B., Pfannes, L., Loeliger, K., Tucker, Z., Tian, X., Kwak, M., Wilhelm, F., Yong, A.S., Maric, I., Maniar, M., Scheinberg, P., Groopman, J., Young, N.S. & Sloand, E.M. (2012) Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na. Leukemia Research, 36, 982-989.
19. Oussenko, I.A., Holland, J.F., Reddy, E.P. & Ohnuma, T. (2011) Effect of ON 01910.Na, an anticancer mitotic inhibitor, on cell-cycle progression correlates with RanGAP1 hyperphosphorylation. Cancer Research, 71, 4968-4976.
20. Prasad, A., Park, I.W., Allen, H., Zhang, X., Reddy, M.V., Boominathan, R., Reddy, E.P. & Groopman, J.E. (2009) Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells. Oncogene, 28, 1518-1528.
21. Prebet, T., Gore, S.D., Esterni, B., Gardin, C., Itzykson, R., Thepot, S., Dreyfus, F., Rauzy, O.B., Recher, C., Ades, L., Quesnel, B., Beach, C.L., Fenaux, P. & Vey, N. (2011) Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. Journal of Clinical Oncology, 29, 3322-3327.
22. Reddy, M.V., Venkatapuram, P., Mallireddigari, M.R., Pallela, V.R., Cosenza, S.C., Robell, K.A., Akula, B., Hoffman, B.S. & Reddy, E.P. (2011) Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2′, 4′, 6′-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): synthesis, structure-activity relationship, and biological activity. Journal of Medicinal Chemistry, 54, 6254-6276.
23. Seetharam, M., Fan, A.C., Tran, M., Xu, L., Renschler, J.P., Felsher, D.W., Sridhar, K., Wilhelm, F. & Greenberg, P.L. (2012) Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na. Leukemia Research, 36, 98-103.
24. Silverman, L.R., Raza, A., Sloand, E.M., Greenberg, P.L. & Wilhelm, F.E. (2010) Overall survival In myelodysplastic syndrome or acute myeloid leukemia patients treated with ON 01910.Na correlates with bone marrow blast response. Blood (ASH Annual Meeting Abstracts), 116, 3998.
25. Trotti, A., Colevas, A.D., Setser, A., Rusch, V., Jaques, D., Budach, V., Langer, C., Murphy, B., Cumberlin, R., Coleman, C.N. & Rubin, P. (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Seminars in Radiation Oncology, 13, 176-181.
26. Vardiman, J.W., Thiele, J., Arber, D.A., Brunning, R.D., Borowitz, M.J., Porwit, A., Harris, N.L., Le Beau, M.M., Hellstrom-Lindberg, E., Tefferi, A. & Bloomfield, C.D. (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937-951.