Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: A randomized phase i study

Cancer Medicine

Volumn 4, Issue 1, 2015, Pages 16-26

  Winer, Eric S ^a   Safran, Howard ^b   Karaszewska, Boguslawa ^c   Richards, Donald A ^d   Hartner, Lee ^e   Forget, Frederic ^f   Ramlau, Rodryg ^g   Kumar, Kirushna ^h   Mayer, Bhabita ⁱ   Johnson, Brendan M ^j   Messam, Conrad A ^j   Mostafa Kamel, Yasser ⁱ  

^a RHODE ISLAND HOSPITAL   (United States)

^b Brown University Oncology Group   (United States)

^c Komed Branch Medical Center   (Poland)

^d TEXAS ONCOLOGY   (United States)

^e Pennsylvania Oncology Hematology Associates   (United States)

^f Center Hospital of the Ardenne Libramont   (Belgium)

^g POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

^h MEENAKSHI MISSION HOSPITAL AND RESEARCH CENTRE   (India)

ⁱ GLAXOSMITHKLINE   (United Kingdom)

^j GLAXOSMITHKLINE   (United States)

more..

Author keywords

Blood platelets; Cancer; Eltrombopag; Thrombocytopenia; Thrombosis

Indexed keywords

CARBOPLATIN; CISPLATIN; ELTROMBOPAG; GEMCITABINE; PLACEBO; ANTINEOPLASTIC AGENT; BENZOIC ACID DERIVATIVE; DEOXYCYTIDINE; HYDRAZINE DERIVATIVE; PYRAZOLE DERIVATIVE;

ADULT; ADVANCED CANCER; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ALOPECIA; ANEMIA; ANXIETY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; CANCER PATIENT; CONSTIPATION; CONTROLLED STUDY; CYSTITIS; DECREASED APPETITE; DEEP VEIN THROMBOSIS; DIZZINESS; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FATIGUE; FEMALE; FEVER; HEADACHE; HUMAN; HYPERCALCEMIA; HYPOALBUMINEMIA; LEUKOPENIA; LIVER TOXICITY; LYMPHOCYTOPENIA; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; MONOTHERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NEPHROTOXICITY; NEUTROPENIA; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SOLID TUMOR; THROMBOCYTE COUNT; THROMBOCYTOPENIA; THROMBOCYTOSIS; URINARY TRACT INFECTION; VOMITING; ANALOGS AND DERIVATIVES; CANCER STAGING; CLINICAL TRIAL; DRUG ADMINISTRATION; MIDDLE AGED; NEOPLASMS; PATHOLOGY; TREATMENT OUTCOME; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENZOATES; DEOXYCYTIDINE; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; HYDRAZINES; MALE; MIDDLE AGED; NEOPLASM STAGING; NEOPLASMS; PLATELET COUNT; PYRAZOLES; TREATMENT OUTCOME;

EID: 85005931189     PISSN: None     EISSN: 20457634     Source Type: Journal    
DOI: 10.1002/cam4.326     Document Type: Article

References (29)

1. Oettle, H., S. Post, P. Neuhaus, K. Gellert, J. Langrehr, K. Ridwelski, et al. 2007. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267-277. doi: 10.1001/jama.297.3.267
2. Oettle, H., P. Neuhaus, A. Hochhaus, J. T. Hartman, K. Gellert, K. Ridwelski, et al. 2013. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310:1473-1481. doi: 10.1001/jama.2013.279201
3. Scagliotti, G. V., U. Pastorino, J. F. Vansteenkiste, L. Spaggiari, F. Facciolo, T. M. Orlowski, et al. 2012. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J. Clin. Oncol. 30:172-178. doi: 10.1200/JCO.2010.33.7089
4. Dash, A., J. A. Pettus, H. W. Herr, B. H. Bochner, G. Dalbagni, S. M. Donat, et al. 2008. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 113:2471-2477. doi: 10.1002/cncr.23848
5. Wu, Y., S. Aravind, G. Ranganathan, A. Martin, and L. Nalysnyk . 2009. Anemia and thrombocytopenia in patients undergoing chemotherapy for solid tumors: a descriptive study of a large outpatient oncology practice database, 2000-2007. Clin. Ther. 31(Pt 2):2416-2432. doi: 10.1016/j.clinthera.2009.11.020
6. Cairo, M. S. 2000. Dose reductions and delays: limitations of myelosuppressive chemotherapy. Oncology (Williston Park) 14(9 Suppl. 8):21-31.
7. Afdhal, N. H., G. M. Dusheiko, E. G. Giannini, P. J. Chen, K. H. Han, A. Mohsin, et al. 2014. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology 146:442-452. doi: 10.1053/j.gastro.2013.10.012
8. Olnes, M. J., P. Scheinberg, K. R. Calvo, R. Desmond, Y. Tang, B. Dumitriu, et al. 2012. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N. Engl. J. Med. 367:11-19. doi: 10.1056/NEJMoa1200931
9. Kellum, A., A. Jagiello-Gruszfeld, I. N. Bondarenko, R. Patwardhan, C. Messam, and Y. Mostafa Kamel . 2010. 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. Curr. Med. Res. Opin. 26:2339-2346. doi: 10.1185/03007995.2010.510051
10. Chawla, S. P., A. Staddon, A. Hendifar, C. A. Messam, R. Patwardhan, and Y. M. Kamel . 2013. Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide. BMC Cancer 13:121. doi: 10.1186/1471-2407-13-121
11. Pecci, A., P. Gresele, C. Klersy, A. Savoia, P. Noris, T. Fierro, et al. 2010. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood 116:5832-5837. doi: 10.1182/blood-2010-08-304725
12. Bussel, J. B., A. L. Frelinger III, W. B. Mitchell, M. P. Pinheiro, M. C. Barnard, M. Lampa, et al. 2010. Platelet function and response to thrombopoietin mimetics in Wiskott-Aldrich syndrome/X-linked thrombocytopenia. Blood 116, Abstract 1429.
13. Wroblewski, S., W. Shi, P. Mudd, Jr., and M. Aivado . 2010. Eltrombopag in thrombocytopenic patients with advanced myelodysplastic syndromes (MDS) or secondary myeloid leukemia after MDS: a phase I/II study. J. Clin. Oncol. 28(Suppl. 15), Abstract TPS184.
14. Erickson-Miller, C. L., K. Pillarisetti, J. Kirchner, D. J. Figueroa, L. Ottesen, A. M. Martin, et al. 2012. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors. BMC Cancer 12:405. doi: 10.1186/1471-2407-12-405
15. Bauman, J. W., C. T. Vincent, B. Peng, M. B. Wire, D. D. Williams, and J. W. Park . 2011. Effect of hepatic or renal impairment on eltrombopag pharmacokinetics. J. Clin. Pharmacol. 51:739-750. doi: 10.1177/0091270010372106
16. Hayes, S., P. N. Mudd, Jr., D. Ouellet, B. M. Johnson, D. Williams, and E. Gibiansky . 2013. Population PK/PD modeling of eltrombopag in subjects with advanced solid tumors with chemotherapy-induced thrombocytopenia. Cancer Chemother. Pharmacol. 71:1507-1520. doi: 10.1007/s00280-013-2150-9
17. Sederholm, C., G. Hillerdal, K. Lamberg, K. Kolbeck, M. Dufmats, R. Westberg, et al. 2005. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J. Clin. Oncol. 23:8380-8388. doi: 10.1200/JCO.2005.01.2781
18. Steward, W. P. 1998. Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. Br. J. Cancer 78(Suppl. 3):15-19.
19. Tay, S. K., A. Ilanchadran, and T. Y. Tan . 2006. First-line gemcitabine and carboplatin in advanced ovarian carcinoma: a phase II study. BJOG 113:1388-1392. doi: 10.1111/j.1471-0528.2006.01100.x
20. Zatloukal, P., L. Petruzelka, M. Zemanova, V. Kolek, J. Skrickova, M. Pesek, et al. 2003. Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer 41:321-331. doi: 10.1016/S0169-5002(03)00233-2
21. Gemzar® (gemcitabine HCl for injection). 2014. US prescribing information. Indianapolis, IN: Eli Lilly and Company. Available at http://pi.lilly.com/us/gemzar.pdf (accessed July 7, 2014).
22. Choi, J. H., S. Y. Oh, H. C. Kwon, J. H. Kim, J. H. Lee, S. Lee, et al. 2008. Gemcitabine versus gemcitabine combined with cisplatin treatment locally advanced or metastatic pancreatic cancer: a retrospective analysis. Cancer Res. Treat. 40:22-26. doi: 10.4143/crt.2008.40.1.22
23. Poplin, E., Y. Feng, J. Berlin, M. C. Rothenberg, H. Hochster, E. Mitchell, et al. 2009. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J. Clin. Oncol. 27:3778-3785.
24. Moskowitz, C. H., P. A. Hamlin, J. Gabrilove, J. R. Bertino, C. S. Portlock, D. J. Straus, et al. 2007. Maintaining the dose intensity of ICE chemotherapy with a thrombopoietic agent, PEG-rHuMGDF, may confer a survival advantage in relapsed and refractory aggressive non-Hodgkin lymphoma. Ann. Oncol. 18:1842-1850. doi: 10.1093/annonc/mdm341
25. Kindler, H. L., D. Niedzwiecki, D. Hollis, S. Sutherland, D. Schrag, H. Hurwitz, et al. 2010. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J. Clin. Oncol. 28:3617-3622. doi: 10.1200/JCO.2010.28.1386
26. Lyman, G. H., A. A. Khorana, N. M. Kuderer, A. Y. Lee, J. I. Arcelus, E. P. Balaban, et al. 2013. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J. Clin. Oncol. 31:2189-2204. doi: 10.1200/JCO.2013.49.1118
27. Erhardt, J. A., C. L. Erickson-Miller, M. Aivado, M. Abboud, K. Pillarisetti, and J. R. Toomey . 2009. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp. Hematol. 37:1030-1037. doi: 10.1016/j.exphem.2009.06.011
28. Psaila, B., J. B. Bussel, M. D. Linden, B. Babula, Y. Li, M. R. Barnard, et al. 2012. In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation. Blood 119:4066-4072. doi: 10.1182/blood-2011-11-393900
29. Vadhan-Raj, S., S. Patel, C. Bueso-Ramos, J. Folloder, N. Papadopolous, A. Burgess, et al. 2003. Importance of predosing of recombinant human thrombopoietin to reduce chemotherapy-induced early thrombocytopenia. J. Clin. Oncol. 21:3158-3167. doi: 10.1200/JCO.2003.08.003