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Malignant pleural mesothelioma (MPM) is a rapidly progressive invariably lethal tumor. Treatment options remain limited and the outcome in relapsed disease is poor warranting new therapeutic options. Following our previous experience in the first-line setting, we conducted a phase 2 open-label non-comparative study to assess the safety and efficacy of weekly vinorelbine chemotherapy, each cycle consisting of 30 mg/m(2) for 6 weeks, in patients with previous exposure to chemotherapy. In 63 individuals with relapsed MPM who had not received previous vinorelbine, we observed an objective response rate of 16% and an overall survival of 9.6 months (95% confidence interval 7.3-11.8 months). The main grade III/IV toxicity observed was neutropenia and toxicity was similar to weekly vinorelbine when used in the first-line setting. Weekly vinorelbine appeared to have a reasonable response rate with an acceptable toxicity profile in the second-line treatment of MPM. Its use should be prospectively evaluated in a randomised trial in the first or second-line therapy of MPM.

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There is no standard therapy for relapsed small cell lung cancer (rSCLC). We evaluated the efficacy and toxicity of a new triplet consisting of irinotecan (100 mg/m(2) Days 1 and 15 q28), cisplatin (40 mg/m(2) Days 1 and 15 q28) and mitomycin (6 mg/m(2) d1 q28) administered to a maximum of 6 cycles in individuals with rSCLC that had relapsed following first line treatment. Partial remissions were observed in 35% and progression in 30% of patients. Progression free survival measured 4.5 months (95% CI 0.8-8.2) and overall survival was 7.8 months (95% CI 5.3-10.3). QoL showed improvement in activity symptoms and stabilization of physical symptoms. As IPM was a well-tolerated regimen with activity in rSCLC, a phase III trial comparing this triplet with other regimens in this setting is warranted.

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BACKGROUND: Malignant pleural mesothelioma (MPM) is a rapidly progressive lethal tumor. Treatment options remain limited and the outcome in recurrent disease is poor. METHODS: A Phase II open-label noncomparative study was conducted to assess the safety and efficacy of the triplet combination irinotecan, cisplatin, and mitomycin-C (IPM) chemotherapy in untreated patients and in those with previous exposure to chemotherapy. RESULTS: In 62 patients an objective response rate of 25% was observed. In the first-line setting progression-free survival measured 6.4 months (95% confidence interval [CI]: 4.5-7.3) and overall survival was 10.8 months (95% CI: 7.9-13.7). In the second-line setting progression-free survival was 7.3 months (95% CI: 3.4-11.2) and overall survival was also 7.3 months (95% CI: 4.8-9.8). Psychosocial well-being improved during chemotherapy and the main toxicity observed was neutropenia (40%). CONCLUSIONS: IPM appeared to have a reasonable response rate with an acceptable toxicity profile in the first- and second-line treatment of MPM.

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Our understanding of malignant mesothelioma has increased rapidly in the last 5 years. The prognosis remains poor for most patients, however. Radical surgery is inappropriate for most, and palliative chemotherapy can be toxic if used without care. Patient selection is crucial, and prognostic factors allow us to predict which patients are likely to benefit from intensive treatment. Longer survival is associated with epithelioid histology, earlier stage, female gender, left-sided primary, nonexposure to asbestos, no history of smoking, and a lack of symptoms at presentation. Numerous genes of significance are identified and many have been shown to correlate with clinical outcome. Molecular data will provide prognostication of exceptional accuracy, biologic insights, and targets for improved treatment.

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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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Prognostic factors in oncology may help physicians give their patients a prognosis for their disease and thus allow them to make plans for the future. These factors also assist in the selection of patients more likely to benefit from intensive treatments, especially in the context of clinical trials. Recently it has become clear that prognostic factors may have an additional benefit: they may provide insight into the biology of the cancer being studied and lead to improved understanding of the molecular pathogenesis. For malignant mesothelioma, the prognostic scoring systems of the Cancer and Leukemia Group B (CALGB) and European Organization for Research and Treatment of Cancer (EORTC) are the most useful of those currently available. These systems rate performance status, age, histological subtype, weight loss, and hematological parameters as the best prognostic factors for malignant mesothelioma. In the future, biological markers may provide additional information on mesothelioma and will help in prognostication.

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