Phase i trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl + hematological malignancies

Cancer Chemotherapy and Pharmacology

Volumn 69, Issue 6, 2012, Pages 1657-1667

  Bose, Prithviraj ^a,b   Perkins, Edward B ^a,b   Honeycut, Connie ^a   Wellons, Martha D ^a   Stefan, Tammy ^c   Jacobberger, James W ^c   Kontopodis, Emmanouil ^d,e   Beumer, Jan H ^e,f   Egorin, Merrill J ^e,g   Imamura, Chiyo K ^h   Figg Sr , W Douglas ⁱ   Karp, Judith E ^j   Koc, Omer N ^k   Cooper, Brenda W ^c   Luger, Selina M ^l   Colevas, A Dimitrios ^m   Roberts, John D ^a,b   Grant, Steven ^a,b,n  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c CASE WESTERN RESERVE UNIVERSITY   (United States)

^d UNIVERSITY HOSPITAL OF HERAKLION   (Greece)

^e UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

^f UNIVERSITY OF PITTSBURGH   (United States)

^g UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^h KEIO UNIVERSITY   (Japan)

ⁱ NATIONAL CANCER INSTITUTE   (United States)

^j JOHNS HOPKINS UNIVERSITY   (United States)

^k TAUSSIG CANCER INSTITUTE   (United States)

^l UNIVERSITY OF PENNSYLVANIA   (United States)

^m STANFORD UNIVERSITY MEDICAL CENTER   (United States)

ⁿ VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

more..

Author keywords

Alvocidib; Bcr Abl; CDK inhibitor; Cyclin dependent kinase inhibitor; Flavopiridol; Imatinib; Tyrosine kinase inhibitor

Indexed keywords

2 [2 METHYL 5 [4 (1 PIPERAZINYLMETHYL)BENZAMIDO]ANILINO] 4 (3 PYRIDYL)PYRIMIDINE; BCR ABL PROTEIN; FLAVOPIRIDOL; HYDROXYUREA; IMATINIB; PROTEIN MCL 1; STAT5 PROTEIN;

ACUTE LYMPHOCYTIC LEUKEMIA; ADULT; AGED; ANEMIA; AREA UNDER THE CURVE; ARTICLE; BLAST CELL; BLOOD CELL COUNT; BONE MARROW SUPPRESSION; CELL COUNT; CHOLECYSTECTOMY; CHOLECYSTITIS; CHRONIC MYELOID LEUKEMIA; CLINICAL ARTICLE; CONTINUOUS INFUSION; CORRELATION ANALYSIS; DIARRHEA; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG FATALITY; DRUG HALF LIFE; DRUG TOLERABILITY; FEBRILE NEUTROPENIA; FEMALE; HUMAN; HUMAN CELL; HYPOPHOSPHATEMIA; INFECTION; LEUKOPENIA; LYMPHOCYTOPENIA; MALE; MULTIPLE CYCLE TREATMENT; MULTIPLE ORGAN FAILURE; NEUTROPENIA; PHASE 1 CLINICAL TRIAL; PHILADELPHIA CHROMOSOME POSITIVE CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; THROMBOCYTOPENIA; TREATMENT RESPONSE;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CYCLIN-DEPENDENT KINASES; FEMALE; FLAVONOIDS; FUSION PROTEINS, BCR-ABL; HUMANS; LEUKEMIA; MALE; MIDDLE AGED; PIPERAZINES; PIPERIDINES; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PYRIMIDINES;

EID: 84863806046     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-012-1839-5     Document Type: Article

References (45)

1. Deininger MWN, Goldman JM, Melo JV (2000) The molecular biology of chronic myeloid leukemia. Blood 96:3343-3356
2. O'Brien SG, Guilhot F, Larson RA et al (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994-1004
3. Fielding AK (2010) How I treat Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 116:3409-3417
4. Clarke MF (2004) Chronic myelogenous leukemia-identifying the Hydra's heads. N Engl J Med 351:634-636
5. Schiffer CA (2007) BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med 357:258-265
6. Krause DS, Van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N Engl J Med 353:172-187
7. Goldman JM (2007) How I treat chronic myeloid leukemia in the imatinib era. Blood 110:2828-2837
8. Dai Y, Grant S (2003) Cyclin-dependent kinase inhibitors. Curr Opin Pharmacol 3:362-370
9. Blagosklonny MV (2004) Flavopiridol, an inhibitor of transcription. Cell Cycle 3:1537-1542
10. Shapiro GI (2004) Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin Cancer Res 10:4270s-4275s
11. Chao SH, Price DH (2001) Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo. J Biol Chem 276:31793-31799
12. Grant S, Dent P (2004) Gene profiling and the cyclin-dependent kinase inhibitor flavopiridol: what's in a name? Mol Cancer Ther 3:873-875
13. Senderowicz AM (2002) The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01. Oncologist 7(suppl 3):12-19
14. Dai Y, Yu C, Singh V et al (2001) Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells. Cancer Res 61:5106-5115
15. Yu C, Krystal G, Dent P, Grant S (2002) Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCRABL- positive human leukemia cells. Clin Cancer Res 8:2976-2984
16. Simon R, Freidlin B, Rubinstein L et al (1997) Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89:1138-1147
17. Holkova B, Perkins EB, Ramakrishnan V et al (2011) Phase I trial of bortezomib (PS341; NSC681239) and alvocidib (flavopiridol; NSC649890) in patients with relapsed or refractory B-cell neoplasms. Clin Cancer Res 17(10):3388-3397
18. Carlesso N, Frank DA, Griffin JD (1996) Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J Exp Med 183(3):811-820
19. Ilaria RL Jr, Van Etten RA (1996) P210 and P190 (BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J Biol Chem 271(49): 31704-31710
20. Shuai K, Halpern J, ten Hoeve J et al (1996) Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene 13(2):247-254
21. Jacobberger JW, Sramkoski RM, Frisa PS et al (2003) Immunoreactivity of Stat5 phosphorylated on tyrosine as a cell-based measure of Bcr/Abl kinase activity. Cytometry A 54(2):75-88
22. Karp JE, Passaniti A, Gojo I et al (2005) Phase I and pharmacokinetic study of flavopiridol followed by 1-beta-D-arabinofuranosylcytosine and mitoxantrone in relapsed and refractory adult acute leukemias. Clin Cancer Res 11(23):8403-8412
23. Tan AR, Yang X, Berman A et al (2004) Phase I trial of the cyclin-dependent kinase inhibitor flavopiridol in combination with docetaxel in patients with metastatic breast cancer. Clin Cancer Res 10(15):5038-5047
24. Senderowicz AM, Headlee D, Stinson SF et al (1998) Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J Clin Oncol 16:2986-2999
25. Schwartz GK, Ilson D, Saltz L et al (2001) Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol 19:1985-1992
26. Shapiro GI, Supko JG, Patterson A et al (2001) A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res 7:1590-1599
27. Stadler WM, Vogelzang NJ, Amato R et al (2000) Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II Consortium Study. J Clin Oncol 18:371-375
28. Tan AR, Headlee D, Messman R et al (2002) Phase I clinical and pharmacokinetic study of flavopiridol administered as a daily 1-hour infusion in patients with advanced neoplasms. J Clin Oncol 20:4074-4082
29. Byrd JC, Lin TS, Dalton JT et al (2007) Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood 109:399-404
30. Rathkopf DE, Ilson DH, Yi S et al (2004) A phase II trial of sequential paclitaxel and flavopiridol in patients with metastatic paclitaxel-refractory esophageal cancer. Presented at the American society of clinical oncology gastrointestinal cancers symposium, San Francisco, CA, January 22-24, 2004 (abstract 67)
31. Rathkopf DE, Fornier M, Shah MA et al (2004) A phase I dosefinding study of weekly, sequential docetaxel (Doc) followed by flavopiridol (F) in patients with advanced, solid tumors. J Clin Oncol 2004(22):213s suppl; abstr 3072
32. Shah MA, Kortmansky J, Motwani M et al (2005) A phase I clinical trial of the sequential combination of irinotecan followed by flavopiridol. Clin Cancer Res 11:3836-3845
33. Lin TS, Blum KA, Fischer DB et al (2010) Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J Clin Oncol 28(3):418-423
34. Karp JE, Blackford A, Smith BD et al (2010) Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk Res 34(7):877-882
35. Karp JE, Smith BD, Resar LS et al (2011) Phase I and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood 117:3302-3310
36. Karp JE, Pagel JM, Smith BD et al (2010) Randomized phase II study of two schedules of flavopiridol (alvocidib, F) given as timed sequential therapy (TST) with Ara-C and mitoxantrone (FLAM) for adults with newly diagnosed, poor-risk acute myelogenous leukemia (AML). Blood (ASH Annual Meeting Abstracts) 2010; 116 (Abstract 186)
37. Peng B, Lloyd P, Schran H (2005) Clinical pharmacokinetics of imatinib. Clin Pharmacokinet 44(9):879-894
38. Deferme S, Van Gelder J, Augustijns P (2002) Inhibitory effect of fruit extracts on P-glycoprotein-related efflux carriers: an in vitro screening. J Pharm Pharmacol 54(9):1213-1219
39. Blum W, Klisovic MA, Phelps RB et al (2010) Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed and refractory acute leukemias. Haematologica 95(7): 1098-1105
40. Houghton PJ, Germain GS, Harwood FC et al (2004) Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res 64(7):2333-2337
41. Robey RW, Medina-Pérez WY, Nishiyama K et al (2001) Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res 7(1):145-152
42. Nelson EA, Walker SR, Weisberg E et al (2011) The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood 117:3421-3429
43. Warsch W, Kollmann K, Eckelhart E et al (2011) High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia. Blood 117:3409-3420
44. Dickson MA, Schwartz GK (2009) Development of cell-cycle inhibitors for cancer therapy. Curr Oncol 16(2):36-43
45. Moore AS, Blagg J, Linardopoulos S, Pearson AD (2010) Aurora kinase inhibitors: novel small molecules with promising activity in acute myeloid and Philadelphia-positive leukemias. Leukemia 24(4):671-678