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| |  No Increased Survival With Larotaxel Versus 5-FU in Patients With Advanced Pancreatic Cancer: Presented at ESMO-GI By Chris Berrie BARCELONA, Spain -- July 2, 2010 -- Larotaxel does not increase survival benefit over 5-fluorouracil (5-FU) or capecitabine in previously treated patients with advanced pancreatic cancer, according to a multicentre, randomised, open-label phase 3 study presented here at the European Society for Medical Oncology's 12th World Congress on Gastrointestinal Cancer (ESMO-GI). Larotaxel is a microtubule-interacting agent that has shown promising preclinical activity in a broad spectrum of tumour models. Jean-Luc Van Laethem, MD, co-investigator and clinic chief, Department of Gastroenterology, Hôpital Erasme, Brussels, Belgium, presented this study June 30 on behalf of the PAPRIKA study investigators. The poor survival and lack of a standard second-line treatment for patients with advanced pancreatic cancer led investigators to evaluate if larotaxel prolongs overall survival (OS) in this patient population. Patients were randomised to 5-FU 1,000 mg/m2/day continuous IV over 4 days or capecitabine 1,000 mg/m2 twice daily from day 1 to day 14 (5-FU arm; n = 204), or to larotaxel 75 mg/m2 IV over 1 hour, on day 1 (n = 204). Baseline clinical characteristics were similar between the treatment groups: median age (5-FU, 60 y vs larotaxel, 65 y), Eastern Cooperative Oncology Group Performance Status Scale (ECOG-PS) 0/1 (37.7%/60.8%), largely metastatic disease (92.6% vs 93.1%), with mainly pancreas (69.6% vs 72.5%) and liver (67.2% vs 61.3%) involvement, and advanced prior anticancer treatment (73.5% vs 76.0%) with 2 treatment lines (94.6% for each arm). The primary endpoint was OS in the intent-to-treat patient population, with secondary endpoints of progression-free survival (PFS), overall response rate (ORR), and safety. The median OS for the 5-FU and larotaxel arms was not significantly different: 5.06 versus 4.80 months (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.84-1.30; log-rank P = .69). The same was seen for PFS: 1.91 versus 2.04 months (HR, 1.02; 95% CI, 0.83-1.26). When examined according to patients treated specifically with 5-FU (n = 71) or capecitabine (n = 133), again, no significant differences from larotaxel were apparent (OS: 5.85, 4.40 mo, respectively; PFS: 1.51, 2.20 mo). Treatment-emergent adverse events (AEs) and deaths were similar across the 5-FU and larotaxel arms: any grade, 93.9% versus 98.5%; grades 3/4, 57.4% versus 67.7%; deaths, 16.8% versus 20.0%. The most common all-grade nonhaematological AEs in the 5-FU arm were hand and foot syndrome (22.3% vs 0.5% for larotaxel) and stomatitis/mucositis (27.9% vs 15.7%). Rates of the following AEs were higher in the larotaxel group: fatigue (35.5% vs 55.1%), diarrhoea (29.9% vs 47.0%), nausea (28.9% vs 39.4%), alopecia (3.0% vs 35.4%), constipation (13.7% vs 24.7%), sensory neuropathy (6.6% vs 19.2%), and myalgia (1.0% vs 13.1%). The main grade 3/4 haematological toxicities were neutropenia (6.3% vs 42.1%) and neutropenic complications (0.5% vs 15.7%). For their accompanying univariate prognostic analysis, Dr. Van Laethem noted, "A good ECOG-PS [P = .0003], previous pancreatectomy [P = .0345], an absence of liver involvement [P = .0005], and normal alkaline phosphatase [P = .0003] were good prognosis factors in this setting." Finally, Dr. Van Laethem noted that this PAPRIKA study provides robust results of OS in this setting, while also showing the importance of ECOG-PS and liver involvement as strong prognostic factors. This study was sponsored by sanofi-aventis. [Presentation title: A Phase III Study Comparing Larotaxel to 5-FU (continuous intravenous 5-FU or capecitabine) in Patients With Advanced Pancreatic Cancer (APC) Previously Treated With a Gemcitabine-Containing Regimen. Abstract O-0007]
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