Phase II trial of vinorelbine and oxaliplatin as first-line therapy in malignant pleural mesothelioma
Lung and Mesothelioma Unit, Department of Medical Oncology, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, United Kingdom.Lung Cancer (Impact Factor: 3.96). 03/2005; 47(2):277-81. DOI: 10.1016/j.lungcan.2004.08.005
The incidence of malignant pleural mesothelioma (MPM) is increasing. Treatment options are limited, although recently published data have offered cause for optimism. We reported a response rate of 24% with low toxicity for single agent vinorelbine. Here we report a phase II trial of vinorelbine with oxaliplatin (VO) in patients with untreated MPM. Chemotherapy consisted of vinorelbine 30 mg/m(2), days 1 and 8 of a 21-day-cycle, and oxaliplatin 130 mg/m(2), day 1. Treatment continued up to six cycles. The primary endpoint was objective response. Secondary endpoints were toxicity, progression-free and overall survival. Responses were assessed by modified RECIST criteria. Twenty-six patients were enrolled. There were six partial remissions, 17 patients with stable disease, and three patients with PD. Response rate was 23% (95% confidence interval 9-44%). Median number of cycles delivered was four. Progression-free survival from first treatment was 4.7 months, and overall survival was 8.8 months. One-year-survival was 27%. Toxicity (% of patients with at least one episode of grade 3 or 4 toxicity): neutropenia 18%, phlebitis 12%, malaise 12%, anorexia 12%, nausea and vomiting 12%, constipation 6%. Quality of life assessed by Rotterdam symptom checklist was associated with stabilization or improvement of psychological well-being and lung symptoms in the majority of patients, but deterioration in physical symptoms. CONCLUSION: VO has activity in MPM with most patients responding or having stable disease, although this doublet is associated with significant toxicity.
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Conference Paper: Fast parallel linear equation solvers based on textured decomposition[Show abstract] [Hide abstract]
ABSTRACT: A fast linear equation solver based on recursive textured decompositions is introduced in this paper. The computational time complexity for solving problems of N unknown variables is in the order of one if N processors are available. It is faster than the multigrid method, so far known as the fastest available method for two dimensional Poisson equation, which has time complexity of O(log N). The basic difference between this approach, and classical iterative algorithms, is that different approximations of the system matrix are used in round-robin fashion while one fixed approximation is used in the classical approach. We show that, with proper choice of approximation compositions, the spectral radius of error dynamic is reduced drastically; and with proper decomposition size, the spectral radius will approach to a constant strictly less than one, even if the dimension of the problem tends to infinity. This enables us to devise a parallel algorithm with order one time complexity.
Article: Prognostic factors in mesothelioma[Show abstract] [Hide abstract]
ABSTRACT: Prognostic factors can help clinicians and patients when deciding a treatment plan. Patients in the best prognostic groups can be considered for more intensive or experimental therapy. Alternatively, patients in the best prognostic groups might prefer a period of observation prior to commencement of therapy. For patients with mesothelioma prognostic factors are potentially especially important because of the lack of a widely applicable anatomical staging system. Both the International Mesothelioma Interest Group (IMIG) and Brigham staging systems are of limited relevance to patients not undergoing radical debulking surgery. Radiological prediction of IMIG or Brigham stage is of little value. Review of the best-known prognostic scoring systems from the EORTC and CALGB has shown that the most important predictors of poor prognosis are: poor performance status; non-epithelioid histology; male gender; low hemoglobin; high platelet count; high white blood cell count; and high lactate dehydrogenase (LDH). The EORTC model was validated at St Bartholomew's Hospital in a group of 145 patients treated in sequential phase II chemotherapy trials. For 70 patients treated with vinorelbine, those having the best EORTC prognosis had a median survival of 19.2 months [95% C.I.=14.7-23.7] compared to 9.9 months [95% C.I.=8.5-11.3] for those in the worst group. The suggestion is that all clinical and biological factors relevant to prognosis should be recorded prospectively in mesothelioma patients selected for clinical trials.
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