A phase I pharmacokinetic study of the P-glycoprotein inhibitor, ONT-093, in combination with paclitaxel in patients with advanced cancer

Investigational New Drugs

Volumn 23, Issue 4, 2005, Pages 311-315

  Chi, Kim N ^a   Chia, Stephen K ^a   Dixon, Ross ^b   Newman, Michael J ^b   Wacher, Vince J ^b   Sikic, Branimir ^c   Gelmon, Karen A ^a  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b Ontogen Corporation   (United States)

^c STANFORD UNIVERSITY   (United States)

Author keywords

P glycoprotein; Paclitaxel; Phase I clinical trial

Indexed keywords

2 [4 (3 ETHOXY 1 PROPENYL)PHENYL] 4,5 BIS[4 (2 PROPYLAMINO)PHENYL] 1H IMIDAZOLE; CREMOPHOR; GLYCOPROTEIN P INHIBITOR; ONT 093; PACLITAXEL; UNCLASSIFIED DRUG;

ADULT; ADVANCED CANCER; AGED; ALOPECIA; ANOREXIA; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; BIOLOGICAL ACTIVITY; BRAIN TOXICITY; CANCER PATIENT; CEREBELLUM DISEASE; CHEMOTHERAPY INDUCED EMESIS; CLINICAL ARTICLE; CLINICAL OBSERVATION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIZZINESS; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG FORMULATION; DRUG INDUCED HEADACHE; DRUG TOLERABILITY; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HEMOCONCENTRATION; HUMAN; HYPERBILIRUBINEMIA; MALE; MUCOSA INFLAMMATION; MYALGIA; NAUSEA; NEUTROPENIA; PARAMETER; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; STANDARD; TOXICITY;

ADULT; AGED; ALOPECIA; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; ARTHRALGIA; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; IMIDAZOLES; MALE; MIDDLE AGED; NEOPLASMS; NEUTROPENIA; P-GLYCOPROTEIN; PACLITAXEL; POLYETHYLENE GLYCOLS;

EID: 22144457872     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10637-005-1439-x     Document Type: Article

References (10)

1. Ling, V: Multidrug resistance: Molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol 40(Suppl): S3-S8, 1997
2. Cordon-Carlo C, O'Brien JP, Boccia J, Casals D, Bertino J, Melamed MR: Expression of the multidrug resistance gene product (p-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem 38: 1277-1287, 1990
3. Sikic BI: Pharmacologic approaches to reversing multidrug resistance. Semin Hematol 34: S40-S47, 1997 (suppl 5)
4. Fracasso PM, Brady MF, Moore DH, Walker JL, Rose PG, Letvak L, Grogan TM, McGuire WP: Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: A gynecologic Oncology Group Study. J Clin Oncol 19: 2975-2982, 2001
5. Toppmeyer D, Seidman AD, Pollak M, Russell C, Tkaczuk K, Verma S, Overmoyer B, Garg V, Ette E, Harding MW, Demetri GD: Safety and efficacy of the multidrug resistance inhibitor incel (Biricodar; VX-710) in combination with paclitaxel for advanced breast cancer refractory to paclitaxel. Clin Cancer Res 8: 670-678, 2002
6. Rubin EH, de Alwis DP, Pouliquen I, Green L, Marder P, Lin Y, Musanti R, Grospe SL, Smith SL, Toppmeyer DL, Much J, Kane M, Chaudhary A, Jordan C, Burgess M, Slapak CA: A phase I trial of a potent P-glycoprotein inhibitor, Zosuquidar.3HCl trihydrochloride (LY335979), administered orally in combination with doxorubicin in patients with advanced malignancies. Clin Cancer Res 8: 3710-3717, 2002
7. Newman MJ, Rodarte JC, Benbatoul KD, Romano SJ, Zhang C, Krane S, Moran EJ, Uyeda RT, Dixon R, Guns ES, Mayer LD: Discovery and Characterization of OC144-093, a novel inhibitor of P-glycoprotein mediated multidrug resistance. Cancer Res 60: 2964-2972, 2000
8. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92: 205-216, 2000
9. Sonnichsen DS, Liu Q, Schuetz EG, Scheutz JD, Pappo A, Relling MV: Variability in human cytochrome P450 paclitaxel metabolism. J Pharm Exp Therap 275: 566-575, 1995.
10. van Zuylen L, Karlsson MO, Verweij J, Brouwer E, de Bruijn P, Nooter K, Stoter G, Sparreboom A: Pharmacokinetic modeling of paclitaxel encapsulation in Cremophor EL micelles. Cancer Chemother Pharmacol 47: 309-318, 2001