A phase 1 study of SNS-032 (formerly BMS-387032), a potent inhibitor of cyclin-dependent kinases 2, 7 and 9 administered as a single oral dose and weekly infusion in patients with metastatic refractory solid tumors

Investigational New Drugs

Volumn 26, Issue 1, 2008, Pages 59-65

  Heath, Elisabeth I ^a   Bible, Keith ^b   Martell, Robert E ^c   Adelman, Daniel C ^d   LoRusso, Patricia M ^a  

^a WAYNE STATE UNIVERSITY   (United States)

^b MAYO CLINIC   (United States)

^c METHYLGENE INC   (Canada)

^d Sunesis Pharmaceuticals Inc   (United States)

Author keywords

Cyclin dependent kinase inhibitor; Metastatic refractory solid tumors; Phase I

Indexed keywords

CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 7; CYCLIN DEPENDENT KINASE 9; CYCLIN DEPENDENT KINASE INHIBITOR; N [5 (5 TERT BUTYL 2 OXAZOLYLMETHYLTHIO) 2 THIAZOLYL]ISONIPECOTAMIDE;

ABDOMINAL CRAMP; ABDOMINAL PAIN; ACUTE KIDNEY FAILURE; ADULT; AGED; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BILIRUBIN BLOOD LEVEL; BREAST CANCER; CLINICAL ARTICLE; CLINICAL TRIAL; COLON CANCER; CONSTIPATION; COUGHING; CREATININE BLOOD LEVEL; DIARRHEA; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEMALE; FOLLOW UP; HUMAN; HYPERBILIRUBINEMIA; LEUKOPENIA; LUNG NON SMALL CELL CANCER; LYMPHOMA; MALE; MAXIMUM TOLERATED DOSE; METASTASIS; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OPEN STUDY; PAIN; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROSTATE CANCER; QT PROLONGATION; RECOMMENDED DRUG DOSE; SENSORY NEUROPATHY; SIDE EFFECT; SINGLE DRUG DOSE; SOLID TUMOR; STEADY STATE; THROMBOCYTOPENIA; TREATMENT RESPONSE;

ADMINISTRATION, ORAL; ADULT; AGED; ANEMIA; ANGIOGENESIS INHIBITORS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; CDC2-CDC28 KINASES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HALF-LIFE; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; NEOPLASM METASTASIS; NEOPLASMS; NEUTROPENIA; RADIOTHERAPY, ADJUVANT; THIAZOLES; TIME FACTORS; TREATMENT OUTCOME;

EID: 38149008164     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10637-007-9090-3     Document Type: Article

References (12)

1. Santamaria D, Ortega S (2006) Cyclins and CDKS in development and cancer: lessons from genetically modified mice. Front Biosci 11:1164-1188
2. Nuwayhid SJ, Hyde J, Aleshin A, Walker DH, Arkin MR (2006) SNS-032 is a potent and selective inhibitor of CDK2,7, and 9 and induces cell death by inhibiting cell cycle progression and the expression of antiapoptotic proteins, 491.
3. Muller-Tidow C, Metzger R, Kugler K, Diederichs S, Idos G, Thomas M, et al (2001) Cyclin E is the only cyclin-dependent kinase 2-associated cyclin that predicts metastasis and survival in early stage non-small cell lung cancer. Cancer Res 61(2):647-653
4. Hunt KK, Keyomarsi K (2005) Cyclin E as a prognostic and predictive marker in breast cancer. Semin Cancer Biol 15(4):319-326
5. Kawana H, Tamaru J, Tanaka T, Hirai A, Saito Y, Kitagawa M, et al (1998) Role of p27Kip1 and cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer. Am J Pathol 153(2):505-513
6. Lee FYF (2001) In vivo antitumor efficacy of BMS-387032, a CDK inhibitor: Bristol Myers Squibb Pharmaceutical Research Institute, May 8
7. Iciek L. BMS-387032 Toxicology Integrated Summary (2001) Bristol Myers Squibb Pharmaceutical Research Institute, May 8
8. Iciek L (2001) BMS-387032 Single dose intravenous investigative toxicity study in dogs (Study Number DS0116): Bristol Myers Squibb Pharmaceutical Research Institute
9. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205-216
10. Grendys EC, Jr., Blessing JA, Burger R, Hoffman J (2005) A phase II evaluation of flavopiridol as second-line chemotherapy of endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 98(2):249-253
11. Burdette-Radoux S, Tozer RG, Lohmann RC, Quirt I, Ernst DS, Walsh W, et al (2004) Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma. Invest New Drugs 22(3):315-322
12. Liu G, Gandara DR, Lara PN, Jr., Raghavan D, Doroshow JH, Twardowski P, et al (2004) A Phase II trial of flavopiridol (NSC #649890) in patients with previously untreated metastatic androgen-independent prostate cancer. Clin Cancer Res 10(3):924-928