A phase II study of the halichondrin B analog eribulin mesylate in gemcitabine refractory advanced pancreatic cancer

详细信息    查看全文

• 作者：Daniel J. Renouf (1)
  Patricia A. Tang (2)
  Pierre Major (3)
  Monika K. Krzyzanowska (1)
  Bindi Dhesy-Thind (3)
  John R. Goffin (3)
  David Hedley (1)
  Lisa Wang (1)
  L. Doyle (4)
  Malcolm J. Moore (15) Malcolm.moore@uhn.on.ca
• 关键词：Pancreatic cancer &#8211 ; Halichodrin B &#8211 ; Eribulin mesylate &#8211 ; Phase II
• 刊名：Investigational New Drugs
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：30
• 期：3
• 页码：1203-1207
• 全文大小：115.3 KB
• 参考文献：1. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96
  2. Glimelius B, Hoffman K, Sjoden PO et al (1996) Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 7:593–600
  3. Moore MJ, Goldstein D, Hamm J et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the national cancer institute of Canada clinical trials group. J Clin Oncol 25:1960–1966
  4. Van Cutsem E, Vervenne WL, Bennouna J et al (2009) Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 27:2231–2237
  5. Burris HA 3rd, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413
  6. Pelzer U, Kubica K, Stieler J, et al (2008). A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study. J Clin Oncol 26:Abstr 4508
  7. Kulke MH, Blaszkowsky LS, Ryan DP et al (2007) Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol 25:4787–4792
  8. Tang P. Gill S, Au HJ et al (2009) Phase II trial of erlotinib in advanced pancreatic cancer. J Clin Oncol 27
  9. Renouf D, Moore M (2010) Evolution of systemic therapy for advanced pancreatic cancer. Expert Rev Anticancer Ther 10:529–540
  10. Cantore M, Rabbi C, Fiorentini G et al (2004) Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer. Oncology 67:93–97
  11. Demols A, Peeters M, Polus M et al (2006) Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer 94:481–485
  12. Xiong HQ, Varadhachary GR, Blais JC et al (2008) Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer 113:2046–2052
  13. Sudo K, Yamaguchi T, Nakamura K et al (2011) Phase II study of S-1 in patients with gemcitabine-resistant advanced pancreatic cancer. Cancer Chemother Pharmacol 67:249–254
  14. Wolpin BM, Hezel AF, Abrams T et al (2009) Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 27:193–198
  15. Katopodis O, Polyzos A, Kentepozidis N et al (2011) Second-line chemotherapy with capecitabine (xeloda) and docetaxel (taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial. Cancer Chemother Pharmacol 67:361–368
  16. O’Reilly EM, Niedzwiecki D, Hall M et al (2010) A cancer and leukemia group B phase II study of sunitinib malate in patients with previously treated metastatic pancreatic adenocarcinoma (CALGB 80603). Oncologist 15:1310–1319
  17. Tempero MA, Arnoletti JP, Behrman S et al (2010) Pancreatic adenocarcinoma. J Natl Compr Canc Netw 8:972–1017
  18. Jordan MA, Kamath K, Manna T et al (2005) The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther 4:1086–1095
  19. Kuznetsov G, Towle MJ, Cheng H et al (2004) Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res 64:5760–5766
  20. Okouneva T, Azarenko O, Wilson L et al (2008) Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase. Mol Cancer Ther 7:2003–2011
  21. Towle MJ, Salvato KA, Budrow J et al (2001) In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res 61:1013–1021
  22. Bekaii-Saab TS, Villalona-Calero MA (2005) Preclinical experience with docetaxel in gastrointestinal cancers. Semin Oncol 32:S3–S9
  23. Saif MW, Syrigos K, Penney R et al (2010) Docetaxel second-line therapy in patients with advanced pancreatic cancer: a retrospective study. Anticancer Res 30:2905–2909
  24. Turrini O, Ychou M, Moureau-Zabotto L et al (2010) Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: new neoadjuvant regimen was safe and provided an interesting pathologic response. Eur J Surg Oncol 36:987–992
  25. Kuznetsov G, TenDyke K, Yu MJ et al (2007) Antiproliferative effects of halichondrin B analog eribulin mesylate (E7389) against paclitaxel-resistant human cancer cells in vitro. Proc Am Assoc Cancer Res 48:275
  26. Konig J, Hartel M, Nies AT et al (2005) Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma. Int J Cancer 115:359–367
  27. (2005) E7389 investigator’s brochure: Eisai medical research INc.
  28. Akada M, Crnogorac-Jurcevic T, Lattimore S et al (2005) Intrinsic chemoresistance to gemcitabine is associated with decreased expression of BNIP3 in pancreatic cancer. Clin Cancer Res 11:3094–3101
  29. Vahdat LT, Pruitt B, Fabian CJ et al (2009) Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 27:2954–2961
  30. Cortes J, Vahdat L, Blum JL et al (2010) Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. J Clin Oncol 28:3922–3928
  31. Cortes J, O’Shaughnessy J, Loesch D et al (2011) Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 377:914–923
  32. Goel S, Mita AC, Mita M et al (2009) A phase I study of eribulin mesylate (E7389), a mechanistically novel inhibitor of microtubule dynamics, in patients with advanced solid malignancies. Clin Cancer Res 15:4207–4212
  33. Tan AR, Rubin EH, Walton DC et al (2009) Phase I study of eribulin mesylate administered once every 21 days in patients with advanced solid tumors. Clin Cancer Res 15:4213–4219
  34. Arnold SM, Moon J, Williamson SK, et al (2009) Phase II evaluation of eribulin mesylate (E7389, NSC 707389) in patients with metastatic or recurrent squamous cell carcinoma of the head and neck: Southwest oncology group trial S0618. Invest New Drugs
  35. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1–10
  36. Zee B, Melnychuk D, Dancey J et al (1999) Multinomial phase II cancer trials incorporating response and early progression. J Biopharm Stat 9:351–363
  37. Dent S, Zee B, Dancey J et al (2001) Application of a new multinomial phase II stopping rule using response and early progression. J Clin Oncol 19:785–791
• 作者单位：1. University Health Network-Princess Margaret Hospital, Toronto, ON, Canada2. Tom Baker Cancer Centre, Calgary, AB, Canada3. Juravinski Cancer Centre, Hamilton, ON, Canada4. CTEP, Washington, DC, USA5. Division of Medical Oncology and Hematology, Princess Margaret Hospital, Rm 5鈥?08, 610 University Avenue, Toronto, M5G2M9 Canada
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Pharmacology and Toxicology
  
• 出版者：Springer Netherlands
• ISSN：1573-0646

文摘

Background Eribulin mesylate is a halichondrin B analog that inhibits microtubule dynamics. Pre-clinical studies have suggested anti-tumor activity in pancreatic cancer. This phase II study of eribulin in patients with advanced pancreatic cancer previously treated with gemcitabine was conducted by the Princess Margaret Hospital Phase II consortium. Patients and Methods Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and previous treatment with gemcitabine. The study was a single arm phase II trial using a Simon 2-stage design. The primary endpoint was response rate, secondary endpoints included time to progression and overall survival. Results Fifteen patients were enrolled, 14 received treatment, and 12 were evaluable for response. The median age was 61, and the majority of patients were ECOG performance status 1. Grade 3 or greater adverse events included neutropenia (29%), fatigue (14%), peripheral neuropathy (7%) and thrombosis (7%). There were no complete or partial responses and therefore the study was closed after the first stage. The best response was stable disease in 5/12 (42%) of patients. Of these five patients, three had stable disease for 9 months or greater. Median time to progression was 1.4 months, and median overall survival was 6.1 months. Conclusion Eribulin was well tolerated but did not result in any objective responses in gemcitabine refractory pancreatic cancer. However, several patients had prolonged stable disease, suggesting that further studies of eribulin in pancreatic cancer may be warranted.