European Journal of Cancer
Volume 43, Issue 1 , Pages 55-63 , January 2007

Results from an in vitro and a clinical/pharmacological phase I study with the combination irinotecan and sorafenib

  • K. Mross

      Affiliations

    • Tumour Biology Center at the Albert-Ludwigs-University, Freiburg, Germany
    • Corresponding Author InformationCorresponding author: Tel.: +49 761 206 1833; fax: +49 761 206 1832.
    • ,
  • S. Steinbild

      Affiliations

    • Tumour Biology Center at the Albert-Ludwigs-University, Freiburg, Germany
    • ,
  • F. Baas

      Affiliations

    • Tumour Biology Center at the Albert-Ludwigs-University, Freiburg, Germany
    • ,
  • D. Gmehling

      Affiliations

    • Tumour Biology Center at the Albert-Ludwigs-University, Freiburg, Germany
    • ,
  • M. Radtke

      Affiliations

    • Bayer HealthCare AG, Wuppertal, Germany
    • ,
  • D. Voliotis

      Affiliations

    • Bayer HealthCare AG, Wuppertal, Germany
    • ,
  • E. Brendel

      Affiliations

    • Bayer HealthCare AG, Wuppertal, Germany
    • ,
  • O. Christensen

      Affiliations

    • Bayer HealthCare AG, Elberfeld, Germany
    • ,
  • C. Unger

      Affiliations

    • Tumour Biology Center at the Albert-Ludwigs-University, Freiburg, Germany

Received 28 July 2006 ,Accepted 4 August 2006.

References 

  1. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral anti-tumor activity and targets the Raf/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–7109
  2. Wilhelm S, Chien DS. BAY 43-9006: preclinical data. Current Pharmaceutical Design. 2002;8:2255–2257
  3. Ostman A, Heldin CH. Involvement of platelet-derived growth factor in disease: development of specific antagonists. Adv Cancer Res. 2001;80:1–38
  4. Lima J, Trovisco V, Soares P, et al. BRAF mutations are not a major event in post-Chernobyl childhood thyroid carcinomas. J Clin Endocrinol Metab. 2004;89:4267–4271
  5. Salvatore G, Giannini R, Faviana P, et al. Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2004;89:5175–5180
  6. Kolch W, Kotwaliwale A, Vass K, Janosch P. The role of Raf kinases in malignant transformation. Expert Rev Mol Med. 2002;2002:1–18
  7. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3:11–22
  8. Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 2005;23:965–972
  9. Moore M, Hirte HW, Siu L, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol. 2005;16:1688–1694
  10. Clark JW, Eder JP, Ryan D, Lee R, Lenz H-J. The safety and pharmacokinetics of the multi-targeted tyrosine kinase inhibitor (including Raf kinase and VEGF kinase), BAY 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res. 2005;11:5472–5480
  11. Awada A, Hendlisz A, Gil T, et al. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer. 2005;92:1855–1861
  12. Escudier B, Szczylik C, Eisen T, et al. Randomized phase III trial of the multi-kinase inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). Eur J Cancer Suppl. 2005;3:226;(abstract 794 and oral presentation)
  13. Ratain MJ, Eisen T, Stadler WM, et al. Final findings from a Phase II, placebo controlled, randomized discontinuation trial (RDT) of sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). J Clin Oncol. 2005;23:388s
  14. Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II study of BAY 43-9006 in patients with advanced hepatocellular carcinoma (HCC). Eur J Cancer. 2004;2:16;Abstract 42
  15. Glimelius B. Benefit-risk assessment of irinotecan in advanced colorectal cancer. Drug Saf. 2005;28:417–433
  16. Heim M, Sharifi M, Hilger RA, Scheulen ME, Seeber S, Strumberg D. Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006. Int J Clin Pharmacol Ther. 2003;41:616–617
  17. Vincent R, Bernando V, Chen C, Zhang X, Carter C. Chemotherapy with BAY 43-9006 in combination with Irinotecan or administered as repeated cycles of therapy against the DLD-1 human tumor xenograft. Clin Cancer Res. 2003;44;Abstract 4469
  18. Haaz MC, Rivory L, Riche C, Vernillet L, Robert J. Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions. Cancer Res. 1998;58:468–472
  19. Lathia C, Lettieri J, Cihon F, Gallentine M, Radtke M, Sundaresan P. Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother Pharmacol. 2006;57:685–692
  20. Radtke M, Schmeer K, Hafner FT, Brendel E, Lathia C. Oxidative metabolism of sorafenib. Drug Metab Rev. 2005;37:67
  21. Iyer L, King CD, Whitington PF, et al. Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest. 1998;101:847–854
  22. Gagne JF, Montminy V, Belanger P, Journault K, Gaucher G, Guillemette C. Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Mol Pharmacol. 2002;62:608–617
  23. Hanioka N, Ozawa S, Jinno H, Ando M, Saito Y, Sawada J. Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin. Xenobiotica. 2001;31:687–699
  24. Villeneuve L, Girard H, Fortier LC, Gagne JF, Guillemette C. Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs. J Pharmacol Exp Ther. 2003;307:117–128
  25. Socinski MA, Sandler AB, Miller LL, et al. Irinotecan (CPT-11) in triplet combinations in patients with advanced non small-cell lung cancer: a review and report of a phase I/II trial. Clin Lung Cancer. 2001;2(Suppl 2):S26–S33
  26. Mathijssen RH, Verweij J, de Jonge MJ, Nooter K, Stoter G, Sparreboom A. Impact of body-size measures on irinotecan clearance: alternative dosing recommendations. J Clin Oncol. 2002;20:81–87
  27. Vincent P, Zhang X, Chen C, et al. Preclinical chemotherapy with the Raf kinase inhibitor BAY 43-9006 in combination with gefitinib, vinorelbine, gemcitabine or doxorubicin. Clin Cancer Res 2003;44(2nd ed):Abstract 719.
  28. Siu LL, Awada A, Takimoto CH, et al. A phase I/II trial of BAY 43-9006 and gemcitabine in advanced solid tumors and in advanced pancreatic cancer. Proc Am Soc Clin Oncol. 2004;23:209;Abstract 3059
  29. Richly H, Kupsch P, Passage K, et al. Results of a phase I trial of BAY 43-9006 in combination with doxorubicin in patients with refractory solid tumors. J Clin Oncol. 2004;23:207;Abstract 3049
  30. Flaherty KT, Brose M, Schuchter L, et al. Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. J Clin Oncol. 2004;22:7507;Abstract
  31. Flaherty KT, Lee RJ, Humphries R, O’Dwyer PJ, Schiller J. Phase I trial of BAY 43-9006 in combination with carboplatin (C) and paclitaxel (P). Proc Am Soc Clin Oncol. 2003;22:710
  32. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–345
  33. Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–237

PII: S0959-8049(06)00803-3

doi: 10.1016/j.ejca.2006.08.032

European Journal of Cancer
Volume 43, Issue 1 , Pages 55-63 , January 2007

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