A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients

Investigational New Drugs

Volumn 25, Issue 2, 2007, Pages 139-146

  Flaig, Thomas W ^a   Gustafson, Daniel L ^a   Su, Lih Jen ^a   Zirrolli, Joseph A ^a   Crighton, Frances ^b   Harrison, Gail S ^a   Pierson, A Scott ^a   Agarwal, Rajesh ^a   Glodé, L Michael ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF COLORADO HOSPITAL   (United States)

Author keywords

Phase I; Prostate cancer; Silibinin

Indexed keywords

ALANINE AMINOTRANSFERASE; ANDROGEN; BILIRUBIN; PROSTATE SPECIFIC ANTIGEN; SILIBININ PHOSPHATIDYLCHOLINE COMPLEX; SILIPHOS; UNCLASSIFIED DRUG;

ADULT; AGED; ANEMIA; ARTICLE; BONE PAIN; CANCER PATIENT; CLINICAL ARTICLE; CLINICAL PROTOCOL; CLINICAL TRIAL; DIARRHEA; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; ELECTROCORTICOGRAPHY; FEVER; GASTROINTESTINAL TOXICITY; HALITOSIS; HUMAN; HUMAN TISSUE; HYPERBILIRUBINEMIA; HYPERCALCEMIA; INTESTINE FUNCTION; LIVER TOXICITY; NEUTROPENIA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROSTATE CANCER; SIDE EFFECT; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; CHEMISTRY, PHARMACEUTICAL; DOSE-RESPONSE RELATIONSHIP, DRUG; EXCIPIENTS; FOLLOW-UP STUDIES; GASTROINTESTINAL DISEASES; GLUCURONIDES; HUMANS; LIVER FUNCTION TESTS; MALE; PHOSPHATIDYLCHOLINES; PROSTATIC NEOPLASMS; SILYMARIN; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SPECTROPHOTOMETRY, ULTRAVIOLET;

EID: 33845899681     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10637-006-9019-2     Document Type: Article

References (22)

1. Pares A, Planas R, Torres M, Caballeria J, Viver JM, Acero D, Panes J, Rigau J, Santos J, Rodes J (1998) Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 28:615-621
2. Flora K, Hahn M, Rosen H, Benner K (1998) Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 93:139-143
3. Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B (1989) Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 9:105-113
4. Singh RP, Dhanalakshmi S, Tyagi AK, Chan DC, Agarwal C, Agarwal R (2002) Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels. Cancer Res 62:3063-3069
5. Kohno H, Suzuki R, Sugie S, Tsuda H, Tanaka T (2005) Dietary supplementation with silymarin inhibits 3,2′-dimethyl-4-aminobiphenyl- induced prostate carcinogenesis in male F344 rats. Clin Cancer Res 11:4962-4967
6. Kohno H, Tanaka T, Kawabata K, Hirose Y, Sugie S, Tsuda H, Mori H (2002) Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 101:461-468
7. Vinh PQ, Sugie S, Tanaka T, Hara A, Yamada Y, Katayama M, Deguchi T, Mori H (2002) Chemopreventive effects of a flavonoid antioxidant silymarin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice. Jpn J Cancer Res 93:42-49
8. Singh RP, Mallikarjuna GU, Sharma G, Dhanalakshmi S, Tyagi AK, Chan DC, Agarwal C, Agarwal R (2004) Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor kappaB-mediated inducible chemoresistance. Clin Cancer Res 10:8641-8647
9. Lahiri-Chatterjee M, Katiyar SK, Mohan RR, Agarwal R (1999) A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res 59:622-632
10. Zi X, Agarwal R (1999) Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci U S A 96:7490-7495
11. Zi X, Grasso AW, Kung HJ, Agarwal R (1998) A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells. Cancer Res 58:1920-1929
12. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279:563-566
13. Singh RP, Sharma G, Dhanalakshmi S, Agarwal C, Agarwal R (2003) Suppression of advanced human prostate tumor growth in athymic mice by silibinin feeding is associated with reduced cell proliferation, increased apoptosis, and inhibition of angiogenesis. Cancer Epidemiol Biomarkers Prev 12:933-939
14. Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E (1990) Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. Eur J Drug Metab Pharmacokinet 15:333-338
15. Schandalik R, Perucca E (1994) Pharmacokinetics of silybin following oral administration of silipide in patients with extrahepatic biliary obstruction. Drugs Exp Clin Res 20:37-42
16. Hoh C, Boocock D, Marczylo T, Singh R, Berry DP, Dennison AR, Hemingway D, Miller A, West K, Euden S, Garcea G, Farmer PB, Steward WP, Gescher AJ (2006) Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences. Clin Cancer Res 12:2944-2950
17. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S (2004) Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos 32:314-320
18. Sridar C, Goosen TC, Kent UM, Williams JA, Hollenberg PF (2004) Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 32:587-594
19. Wasserman E, Myara A, Lokiec F, Goldwasser F, Trivin F, Mahjoubi M, Misset JL, Cvitkovic E (1997) Severe CPT-11 toxicity in patients with Gilbert's syndrome: two case reports. Ann Oncol 8:1049-1051
20. van Erp NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW, Sparreboom A, Gelderblom H (2005) Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 11:7800-7806
21. Dhanalakshmi S, Agarwal P, Glode LM, Agarwal R (2003) Silibinin sensitizes human prostate carcinoma DU145 cells to cisplatin-and carboplatin-induced growth inhibition and apoptotic death. Int J Cancer 106:699-705
22. Chlopcikova S, Psotova J, Miketova P, Simanek V (2004) Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans. Phytother Res 18:107-110