A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) ixabepilone, in patients with advanced pancreas cancer: A Southwest Oncology Group study
Purpose: The purpose of this Phase II multi-institutional study was to define the efficacy and toxicity of ixabepilone in patients with advance pancreatic adenocarcinoma.
Patients and methods: Patients were required to have pancreatic adenocarcinoma and metastatic or recurrent disease that was not amenable to curative resection. Performance status was 0-1, and patients could not have had prior chemotherapy, or chemoradiation therapy for their advanced disease although prior local palliative radiation was allowed. Ixabepilone was administered iv as a 3 hour infusion every 21 days. Initially, the dose was 50 mg/m2 but this was lowered to 40 mg/m2 shortly after the trial opened because of concerns about neurotoxicity.
Results: Sixty-two patients were registered however 2 were ineligible because they did not have recurrent or metastatic disease. For the 60 eligible patients, 22 had performance status of 0 and 38 performance status of 1. The estimated 6-month survival was 60% (95% CI 48%–72%) with a median survival of 7.2 months and an estimated time to treatment failure of 2.3 months. Out of 56 patients with measurable disease there were 5 confirmed partial responses for a confirmed response probability of 9% (95% CI 3%–20%) and 7 unconfirmed partial responses for an overall response probability of 21% (95% CI 12%–34%). Common toxicities were neutropenia/granulocytopenia, nausea and vomiting and neuropathy. There was one death, cause not determined but judged “possibly” related to treatment.
Conclusion: Ixabepilone shows encouraging activity in patients with advanced pancreatic cancer and should be investigated further in this disease.
KeywordsPhase II Epothilone B analogue Ixabepilone Pancreas cancer Southwest Oncology Group
Unable to display preview. Download preview PDF.
- 2.Evans DB, Abbruzzese JL, Willett CG (2001) Cancer of the pancreas. Section 4 of Chapter 33.4, Cancers of the Gastrointestinal Tract. In DeVita VT Jr., Hellman S, Rosenberg SA (eds), Cancer Principles and Practice of Oncology, 6th edn, Lippincott Williams & Wilkins, Philadelphia, pp. 1126–1161Google Scholar
- 3.Burris III HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD (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 15:2403–2413PubMedGoogle Scholar
- 7.Louvet C, Labianca R, Hammel P, Lledo G, de Braud F, Andre T, Cantore M, Ducreux M, Zaniboni A, de Gramont A (2004) GemOx (gemcitabine+oxaliplatin) versus gem (gemcitabine) in non resectable pancreatic adenocarcinoma: Final results of the GERCOR/GISCAD intergroup phase III. J Clin Oncol 22(No 14S) p 315s abstract #4008, (2004 ASCO Meeting Proceedings (Post meeting edition)Google Scholar
- 8.Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schonekas H, Rost A, Neuhaus H, Haag C, Stoffregen C, Clemens M (2003) A phase III trial comparing gemcitabine plus cisplatin vs gemcitabine alone in advanced pancreatic carcinoma. Proceedings ASCO 22: 250, # 1003 (abstract)Google Scholar
- 9.Rocha Lima CM, Green MR, Rotche R, Miller Jr WH, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 22:3776–3783PubMedCrossRefGoogle Scholar
- 13.Whitehead RP, McCoy SA, Rivkin SE, Gross HM, Conrad ME, Abbruzzese JL. (2004) A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) in patients with advanced pancreas cancer: A Southwest Oncology Group Study. Proceedings ASCO 23: p 315, #4012 (abstract)Google Scholar
- 15.Macdonald JS, McCoy S, Whitehead RP, Iqbal S, Wade JL 3rd, Giguere JK, Abbruzzese JL (2005) A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: A Southwest Oncology Group (SWOG-9924) study. Invest New Drugs 23:485–487Google Scholar
- 16.Xiong HQ, Rosenberg A, LoBuglio A, Schmidt W, Wolff RA, Deutsch J, Needle M, Abbruzzese JL (2004) Cetuximab, a monoclonal antibody targeting the epidermal growth factor recptor, in combination with gemcitabine for advanced pancreatic cancer: A multicenter Phase II trial. J Clin Oncol 22:2610–2616PubMedCrossRefGoogle Scholar
- 17.Kindler HL, Friberg G, Stadler WM, Singh DA, Locker G, Nattam S, Kozloff M, Kasza K, Vokes EE (2004) Bevacizumab (B) plus gemcitabine (G) in patients (pts) with advanced pancreatic cancer (PC): Updated results of a multi-center Phase II trial. Proceedings ASCO 23:314, #4009 (abstract)Google Scholar