Single-Agent Versus Combination Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer and a Performance Status of 2: Prognostic Factors and Treatment Selection Based on Two Large Randomized Clinical Trials

Purpose:Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2.Patients and Methods:Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy.Results:Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival times were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0–2 risk factors had similar outcomes independent of treatment, whereas patients with 3–4 factors had a nonsignificant improvement in median survival with combination chemotherapy.Conclusion:Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy

Randomized Phase III Trial Comparing Single-Agent Paclitaxel Poliglumex (CT-2103, PPX) with Single-Agent Gemcitabine or Vinorelbine for the Treatment of PS 2 Patients with Chemotherapy-Naïve Advanced Non-small Cell Lung Cancer

BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) and impaired performance status (PS >or= 2) have limited life expectancies and decreased tolerance for drug-induced toxicities. Current treatment guidelines indicate that PS 2 patients benefit from systemic therapy. Further refinement of treatment in these patients requires reduction of treatment-associated toxicities while maintaining or improving efficacy. Paclitaxel poliglumex (PPX), a macromolecular polymer-drug conjugate of paclitaxel and poly-l-glutamic acid, may enhance the therapeutic index of paclitaxel. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC randomly received single-agent PPX (175 mg/m) or a comparator (single-agent vinorelbine or gemcitabine). The primary end point of this study was overall survival. RESULTS: Overall survival was similar between treatment arms (hazard ratio [HR] = 0.95; log-rank p = 0.686). Median and 1-year survival were 7.3 months and 26%, respectively, for PPX versus 6.6 months and 26% for the control arm. There was a nonsignificant trend toward improved survival in women in the PPX arm compared with standard single agents (HR = 0.65; p = 0.069). The most frequent grade 3/4 adverse events in the treatment versus control arm were dyspnea (13% versus 17%, respectively) and fatigue (10% versus 9%). Grade 3/4 neutropenia and anemia were reduced in the PPX arm (2% versus 8% and 3% versus 9%, respectively). Neuropathy, a taxane-specific toxicity, was more common in the PPX arm; grade 3 neuropathy was limited to 3%. CONCLUSIONS: Single-agent PPX, dosed at 175 mg/m, is active and well tolerated in PS 2 patients with advanced NSCLC. Patients on PPX required fewer red blood cell transfusions, hematopoietic growth factors, opioid analgesics, and clinic visits than patients receiving gemcitabine or vinorelbine

Sheep Updates 2008 - part 3

This session covers fiveteen papers from different authors: CONTROLLING FLY STRIKE 1. Breeding for Blowfly Resistance - Indicatoe Traits, LJE Karlsson, JC Greeff, L Slocombe, Department of Agriculture & Food, Western Australia 2.A practical method to select for breech strike resistance in non-pedigreed Merino flocks, LJE Karlsson, JC Greeff, L Slocombe, K. Jones, N. Underwood, Department of Agriculture & Food, Western Australia 3. Twice a year shearing - no mulesing, Fred Wilkinson, Producer, Brookton WA BEEF 4. Commercial testing of a new tool for prediction of fatness in beef cattle, WD HoffmanA, WA McKiernanA, VH OddyB, MJ McPheeA, Cooperative Research Centre for Beef Genetic Technologies, A N.S.W. Deptartment of Primary Industries, B University of New England 5. A new tool for the prediction of fatness in beef cattle, W.A. McKiernanA, V.H. OddyB and M.J. McPheeC; Cooperative Research Centre for Beef Genetic Technologies, A N.S.W. Dept of Primary Industries, B University of New England, C N.S.W. Dept of Primary Industries Beef Industry Centre of Excellence. 6. Effect of gene markers for tenderness on eating quality of beef, B.L. McIntyre, CRC for Beef Genetic Technologies, Department of Agriculture and Food WA 7. Accelerating beef industry innovation through Beef Profit Partnerships, Parnell PF1,2, Clark RA1,3, Timms J1,3, Griffith G1,2, Alford A1,2, Mulholland C1 and Hyland P1,4,1Co-operative Research Centre for Beef Genetic Technologies; 2NSW Department of Primary Industries; 3 Qld Department of Primary Industries and Fisheries; 4The University of Queensland. SUSTAINABILITY 8. The WA Sheep Industry - is it ethically and environmentally sustainable? Danielle England, Department of Agriculture and Food Western Australia 9. Overview of ruminant agriculture and greenhouse emissions, Fiona Jones, Department of Agriculture and Food Western Australia 10. Grazing for Nitrogen Efficiency, John Lucey, Martin Staines and Richard Morris, Department of Agriculture and Food Western Australia 11. Investigating potential adaptations to climate change for low rainfall farming system, Megan Abrahams, Caroline Peek, Dennis Van Gool, Daniel Gardiner, Kari-Lee Falconer, Department of Agriculture and Food Western Australia SHEEP 12. Benchmarking ewe productivity through on-farm genetic comparisons, Sandra Prosser, Mario D’Antuono and Johan Greeff; Department of Agriculture and Food Western Australia 13. Increasing profitability by pregnancy scanning ewes, John Young1, Andrew Thompson2 and Chris Oldham2; 1Farming Systems Analysis Service, Kojonup, WA, 2Department of Agriculture and Food Western Australia 14. Targeted treatment of worm-affected sheep - more efficient, more sustainable, Brown Besier, Department of Agriculture and Food Western Australia 15. Improving Weaner Sheep Survival, Angus Campbell and Ralph Behrendt, Cooperative Research Centre for Sheep Industry Innovatio

Randomized Phase III Trial Comparing Single-Agent Paclitaxel Poliglumex (CT-2103, PPX) with Single-Agent Gemcitabine or Vinorelbine for the Treatment of PS 2 Patients with Chemotherapy-Naïve Advanced Non-small Cell Lung Cancer

BackgroundPatients with advanced non-small cell lung cancer (NSCLC) and impaired performance status (PS ≥ 2) have limited life expectancies and decreased tolerance for drug-induced toxicities. Current treatment guidelines indicate that PS 2 patients benefit from systemic therapy. Further refinement of treatment in these patients requires reduction of treatment-associated toxicities while maintaining or improving efficacy. Paclitaxel poliglumex (PPX), a macromolecular polymer–drug conjugate of paclitaxel and poly-l-glutamic acid, may enhance the therapeutic index of paclitaxel.MethodsChemotherapy-naive PS 2 patients with advanced NSCLC randomly received single-agent PPX (175 mg/m2) or a comparator (single-agent vinorelbine or gemcitabine). The primary end point of this study was overall survival.ResultsOverall survival was similar between treatment arms (hazard ratio [HR] = 0.95; log-rank p = 0.686). Median and 1-year survival were 7.3 months and 26%, respectively, for PPX versus 6.6 months and 26% for the control arm. There was a nonsignificant trend toward improved survival in women in the PPX arm compared with standard single agents (HR = 0.65; p = 0.069). The most frequent grade 3/4 adverse events in the treatment versus control arm were dyspnea (13% versus 17%, respectively) and fatigue (10% versus 9%). Grade 3/4 neutropenia and anemia were reduced in the PPX arm (2% versus 8% and 3% versus 9%, respectively). Neuropathy, a taxane-specific toxicity, was more common in the PPX arm; grade 3 neuropathy was limited to 3%.ConclusionsSingle-agent PPX, dosed at 175 mg/m2, is active and well tolerated in PS 2 patients with advanced NSCLC. Patients on PPX required fewer red blood cell transfusions, hematopoietic growth factors, opioid analgesics, and clinic visits than patients receiving gemcitabine or vinorelbine