A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors

Current Medical Research and Opinion

Volumn 26, Issue 10, 2010, Pages 2339-2346

  Kellum, A ^a   Jagiello Gruszfeld, A ^b   Bondarenko, I N ^c   Patwardhan, R ^d   Messam, C ^d   Kamel, Y Mostafa ^d  

^a North Mississippi Hematology and Oncology Associates LTD   (United States)

^b ZOZ MSWiA z Warmi sko Mazurskim Centrum Onkologii   (Poland)

^c Dnipropetrovsk State Medical Academy   (Ukraine)

^d GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Carboplatin; Chemotherapy; Eltrombopag; Paclitaxel; Solid tumors; Thrombocytopenia

Indexed keywords

CARBOPLATIN; ELTROMBOPAG; PACLITAXEL; PLACEBO;

ACUTE KIDNEY FAILURE; ADULT; ADVANCED CANCER; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALOPECIA; ANEMIA; ANOREXIA; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BILIRUBIN BLOOD LEVEL; BLEEDING; BONE PAIN; BRAIN ISCHEMIA; BRAIN METASTASIS; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CARDIOPULMONARY INSUFFICIENCY; CARDIOTOXICITY; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG WITHDRAWAL; EYE TOXICITY; FATIGUE; FEMALE; HEMOPTYSIS; HEPATOBILIARY DISEASE; HUMAN; HYPONATREMIA; LEUKOPENIA; LUNG NON SMALL CELL CANCER; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MYALGIA; NAUSEA; NEPHROTOXICITY; NEUTROPENIA; OVARY CANCER; PAIN; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; SENSORY NEUROPATHY; SIDE EFFECT; SOLID TUMOR; THROMBOCYTE COUNT; THROMBOCYTOPENIA; THROMBOEMBOLISM; VOMITING;

ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENZOIC ACIDS; CARBOPLATIN; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; HYDRAZINES; MALE; MIDDLE AGED; NEOPLASMS; PACLITAXEL; PLACEBOS; PLATELET COUNT; POLYPHARMACY; PYRAZOLES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 77956793813     PISSN: 03007995     EISSN: 14734877     Source Type: Journal    
DOI: 10.1185/03007995.2010.510051     Document Type: Article

References (18)

1. Cairo MS. Dose reductions and delays: limitations of myelosuppressive chemotherapy. Oncology (Williston Park) 2000;14(Suppl. 8):21-31
2. Demetri GD. Targeted approaches for the treatment of thrombocytopenia. Oncologist 2001;6(Suppl. 5):15-23
3. PROMACTA® (eltrombopag). Full prescribing information. Research Triangle Park, NC, GlaxoSmithKline, 2008
4. Erickson-Miller C, Delorme E, Giampa L, et al. Biological activity and selectivity for Tpo receptor of the orally bioavailable, small molecule Tpo receptor agonist, SB-497115. ASH Annual Meeting Abstracts 2004 November 16, 2004;104(11):2912
5. Erickson-Miller CL, Delorme E, Tian SS, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells 2009;2;27:424-430
6. Erhardt JA, Erickson-Miller CL, Aivado M, et al. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp Hematol 2009;37:1030-1037
7. Jenkins JM, Williams D, Deng Y, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007;109:4739-4741
8. Bussel JB, Cheng G, SalehMN, etal. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237-2247
9. McHutchison JG, Dusheiko G, Shiffman ML, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007;357:2227-2236
10. Guminski AD, Harnett PR, deFazio A. Carboplatin and paclitaxel interact antagonistically in a megakaryoblast cell line-a potential mechanism for paclitaxel-mediated sparing of carboplatin-induced thrombocytopenia. Cancer Chemother Pharmacol 2001;48:229-234
11. Ishikawa H, Fujiwara K, Suzuki S, et al. Platelet-sparing effect of paclitaxel in heavily pretreated ovarian cancer patients. Int J Clin Oncol 2002;7:330-333
12. Pertusini E, Ratajczak J, Majka M, et al. Investigating the platelet-sparing mechanism of paclitaxel/carboplatin combination chemotherapy. Blood 2001; 97:638-644
13. Gibiansky E, Mudd JPN, Kamel YM. Population pharmacokinetics of eltrombopag in patients with cancer and healthy subjects. AAPS Journal 2009;11(S2):Abstract No 2498
14. Walsky RL, Gaman EA, Obach RS. Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol 2005;45:68-78
15. Gianni L, Vigano L, Locatelli A. Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. J Clin Oncol 1997;15:1906-1915
16. Holmes FA, Madden T, Newman RA. Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1996;14:2713-2721
17. Farese AM, MacVittie TJ, Roskos L, et al. Hematopoietic recovery following autologous bone marrow transplantation in a nonhuman primate: effect of variation in treatment schedule with PEG-rHuMGDF. Stem Cells 2003; 21:79-89
18. Vadhan-Raj S, Trent J, Araujo DM, et al. Evaluation of AMG 531 in chemotherapy-induced thrombocytopenia (CIT): results of a phase I/II study. Abstract e20616. Presented at the 45th Annual Meeting of the American Society of Clinical Oncology. May 29-June 2, 2009, Orlando, FL