A randomized phase III study of rubitecan (ORA) vs. best choice (BC) in 409 patients with refractory pancreatic cancer report from a North-American multi-center study
2004; Lippincott Williams & Wilkins; Volume: 22; Issue: 14_suppl Linguagem: Inglês
10.1200/jco.2004.22.14_suppl.4013
ISSN1527-7755
AutoresAndrew Jacobs, H. A. Burris, Saul E. Rivkin, Paul S. Ritch, Peter D. Eisenberg, K.L. Mettinger,
Tópico(s)Neuroendocrine Tumor Research Advances
Resumo4013 Background: Rubitecan (Orathecin), an oral topoisomerase I inhibitor, showed promising activity in pancreatic cancer in previous single-center Phase 2 studies in US and Europe. Our objective was to compare ORA with BC (physicians' best choice of treatment or care). Primary end-point: Median survival (MS) . Secondary endpoints: Response rate (RR), progression- free survival (PFS) and safety. Methods: ORA was administered orally at a dose of 1.5 mg/m2 for 5 consecutive days each week for 8 or more weeks. BC consisted of standard regimens of best alternative chemotherapy (89%) or supportive care (11%). CT scans were followed every 8 weeks. Results: 198 patients (pts) were randomized to ORA and 211 to BC. More than 90% were resistant to prior chemotherapy and 70% were refractory to 2 or more prior regimens. 49% of BC patients crossed over to rescue therapy with ORA at time of failure. No significant difference was noted in MS time (ORA: 108 days, BC 94 days, p =0.626), whereas a significant survival advantage was observed for BC pts crossed over to ORA vs. BC non-rescue pts, 147 days vs. 60 days (P<0.0001). In pts with measurable disease (59%), there were 12 independently verified ( blinded radiology review) responders for ORA (2 CR and 10 PR) for a RR of 11%, compared to one responder (<1%; 1 CR) for BC (p< 0.001). Stable disease (SD) was also more common on ORA (44 pts vs. 27 pts). On an Intent-To-Treat basis, more than 2-fold more pts on ORA (28% vs. 13%) achieved tumor growth control (CR +PR +SD), a primary objective for palliative treatment in this disease (Heinemann et al., Oncology 60:8–18, 2001). Median PFS was significantly longer for ORA, 58 days vs. 48 days (p =0.003). ORA was well tolerated as <5% discontinued treatment due to toxicity. Grade 3–4 toxicity was more common for ORA (neutropenia 28% vs. 14%; anemia 21% vs. 9%; nausea/vomiting 14% vs. 9%; diarrhea 12% vs. 5%). Conclusions: The results of this study support the notion that rubitecan, a new oral medication with an acceptable risk-benefit ratio, is convenient to use, and can achieve tumor growth control in a disease with few treatment options. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Supergen GlaxoSmithKline GlaxoSmithKline
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