Phase I and pharmacokinetic study of LY293111, an orally bioavailable LTB4 receptor antagonist, in patients with advanced solid tumors

Journal of Clinical Oncology

Volumn 23, Issue 23, 2005, Pages 5365-5373

  Schwartz, Gary K ^a   Weitzman, Aaron ^a   O'Reilly, Eileen ^a   Brail, Les ^a   De Alwis, Dinesh P ^a   Cleverly, Ann ^a   Barile Thiem, Barbara ^a   Vinciguerra, Vincent ^a   Budman, Daniel R ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [2 PROPYL 3 [3 [2 ETHYL 4 (4 FLUOROPHENYL) 5 HYDROXYPHENOXY]PROPOXY]PHENOXY]BENZOIC ACID; ANTIEMETIC AGENT; ANTINEOPLASTIC AGENT; BENZOIC ACID DERIVATIVE; LEUKOTRIENE B4 RECEPTOR;

ABDOMINAL PAIN; ADRENAL CORTEX CARCINOMA; ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BILE DUCT CARCINOMA; CANCER GROWTH; CHONDROSARCOMA; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL CARCINOMA; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG RESPONSE; DRUG STRUCTURE; DRUG TOLERABILITY; ESOPHAGEAL ADENOCARCINOMA; FEMALE; FLATULENCE; HUMAN; HYPERBILIRUBINEMIA; HYPERCALCEMIA; HYPERKALEMIA; HYPERNATREMIA; HYPERURICEMIA; HYPOALBUMINEMIA; HYPOCALCEMIA; HYPOKALEMIA; HYPONATREMIA; INSOMNIA; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG SMALL CELL CANCER; LYMPHOCYTOPENIA; MALE; MELANOMA; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPHIL; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROSTATE CANCER; SARCOMA; SIDE EFFECT; SOLID TUMOR; STEADY STATE; THROMBOCYTE; THYROID CANCER; VOMITING; DRUG ANTAGONISM; MAXIMUM TOLERATED DOSE; METABOLISM; MIDDLE AGED; NEOPLASM; ORAL DRUG ADMINISTRATION; SAFETY;

ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; AREA UNDER CURVE; BENZOIC ACIDS; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; RECEPTORS, LEUKOTRIENE B4; SAFETY;

EID: 23944487244     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.2005.02.766     Document Type: Article

References (22)

1. Tang DG, Chen YQ, Honn KV: Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis. Proc Natl Acad Sci USA 93:5241-5246, 1996
2. Teicher BA, Korbut TT, Menon K, et al: Cyclooxygenase and lipoxygenase inhibitors as modulators of cancer therapies. Cancer Chemother Pharmacol 33:515-522, 1994
3. Teicher BA, Holden SA, Herman TS, et al: Modulation of [cisdiamminedichloroplatinum(II)/ hyperthermial therapy by inhibitors of arachidonic acid metabolism. Int J Onoco 4:17-22, 1994
4. Ara G, Teicher BA: Cyclooxygenase and lipoxygenase inhibitors in cancer therapy. Prostaglandins Leukot Essent Fatty Acids 54:3-16, 1996
5. Bortuzzo C, Hanif R, Kashfi K, et al: The effect of leukotrienes B and selected HETEs on the proliferation of colon cancer cells. Biochim Biophys Acta 1300:240-246, 1996
6. el-Hakim I, Langdon JD, Zakrzowski JT, et al: Leukotriene Bgamma and oral cancer. Br J Oral Maxillofac Surg 28:155-157, 1990
7. Ding XZ, Iversen P, Cluck MW, et al: Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells. Biochem Biophys Res Commun 261:218-223, 1999
8. Ghosh J, Myers CE: Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc Natl Acad Sci USA 95:13182-13187, 1998
9. Rioux N, Castonguay A: Inhibitors of lipoxygenase: A new class of cancer chemopreventive agents. Carcinogenesis 19:1393-1400, 1998.
10. Varian J, Filial SEG, Perinea P: Directional motility in strongly malignant murine tumor cells. Int J Cancer 35:558-560, 1985
11. Marder P, Spaethe SM, Froelich LL, et al: Inhibition of ex vivo neutrophil activation by oral LY293111, a novel leukotriene B 4 receptor antagonist. Br J Clin Pharmacol 42:457-464, 1996
12. Jackson WT, Fleisch JH: Development of novel anti-inflammatory agents: A pharmacologic perspective on leukotrienes and their receptor. Prog Drug Res 46:115-168, 1996
13. Sawyer JS, Bach NJ, Baker R, et al: Synthetic and structure/ activity studies on acid-substituted 2-arylphenols: Discovery of 2-[2-propyl-3-[3-[2- ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic acid, a high-affinity leukotriene B4 receptor antagonist. J Med Chem 38:4411-4432, 1995
14. Jackson WT, Froelich LL, Boyd RJ, et al: Pharmacologic actions of the second-generation leukotriene B4 receptor antagonist LY293111: in vitro studies. J Pharmacol Exp Ther 288:286-294, 1999
15. Tong WG, Ding XZ, Hennig R, et al: Leukotriene B4 receptor antagonist LY293111 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Clin Cancer Res 8:3232-3242, 2002
16. Marshall M, Diaz HB, Brozinick J, et al: LY293111 inhibits tumor cell growth in vitro through an apparent PPARγ agonist activity. Proc Amer Assoc Cancer Res 43: 957, 2002 (abstr 4741).
17. Smith BP, Vandenhende VR, DeSante KA, et al: Confidence interval criteria for assessment of dose proportionality. Pharm Res 17:1278-1283, 2000
18. Buechler C, Ritter M, Duong CQ, et al: Adipophilin is a sensitive marker for lipid loading in human blood monocytes. Biochim Biophys Acta 1532:97-104, 2001
19. Tontonoz P, Nagy L, Alvarez J, et al: PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93:241-252, 1998
20. Hennig R, Ding XZ, Tong WG, et al: 5-Lipoxygenase and leukotriene B(4) receptor are expressed in human pancreatic cancers but not in pancreatic ducts in normal tissue. Am J Pathol 161:421-428, 2002
21. Hennig R, Ding XZ, Tong WG, et al: Effect of LY293111 in combination with gemcitabine in colonic cancer. Cancer Lett 210:41-46, 2004
22. Budman DR, Calabro A: Studies of synergistic and antagonistic combinations of conventional cytotoxic agents with the multiple eiconsanoid pathway modulator LY293111. Anticancer Drugs 15:1-5, 2004