Article

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: 3.74). 03/2005; 47(2):277-81. DOI: 10.1016/j.lungcan.2004.08.005
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
70 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor issued from the mesothelial surface of the pleural space. A previous exposure to asbestos is the main risk factor of mesothelioma. Clinical signs are most of the time late and unspecific. Chest CT-scan, a key imaging procedure, usually shows a (unilateral) pleurisy associated with pleural nodular thickening. PET-scan associated with CT-scan may help to differenciate MPM from pleural benign tumors but it is not recommended for the diagnosis of MPM, as well as chest resonance magnetic imaging and blood or pleural fluid biomarkers, including soluble mesothelin still under investigation. The diagnosis of MPM is based on histology using essentially immunohistochemistry on pleural biopsies best obtained by thoracoscopy. The treatment of MPM relies mostly on chemotherapy. Surgery, pleurectomy/decortication or extrapleural pneumonectomy, is not recommended outside a clinical trial, as well as adjuvant chest radiotherapy. Prophylactic irradiation of chest scars and drains, validated by the French guidelines in 2005, is however highly discussed at the international level. Finally, numerous research studies presently assess the value of targeted therapies and biomarkers in MPM, opening new perspectives in the management of this cancer.
    Revue de Pneumologie Clinique 02/2013; 69(1):26–35. DOI:10.1016/j.pneumo.2012.12.003 · 0.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pemetrexed-platinum chemotherapy is the standard first-line treatment of unresectable malignant pleural mesothelioma (MPM). At progression, patients are generally selected to experimental trials, when available, or, in every-day clinical practice, they are offered second-line chemotherapy. The optimal treatment has not yet been defined. The aim of this retrospective, single-center study was to evaluate the activity and toxicity of vinorelbine administered to a consecutive series of pemetrexed-pretreated MPM patients. Vinorelbine 25mg/m(2) was administered intravenously as a single agent on days 1, 8 every three weeks, either as second-line (2L) or further-line (>2L) therapy. Treatment was repeated for a maximum of 6 cycles, until progression, or unacceptable toxicity. Fifty-nine patients were included in this analysis. Vinorelbine was given to 34 patients as 2L, and to 25 as >2L treatment. The median age was 69 years (range 45-80). Forty-two patients (71.2%) had a good EORTC prognostic score. Partial response was observed in 9 (15.2%) cases, stable disease in 20 (33.9%). The overall disease control rate (DCR) was 49.1%. Median progression-free survival (PFS) and overall survival (OS) were 2.3 and 6.2 months, respectively. ECOG performance status (PS) (HR0 vs. 1-2 0.50; 95%CI: 0.3-0.8; p=0.014) and PFS≥6 months following first-line (FL) chemotherapy (HRFL-PFS>6ms vs. <6ms 0.50; 95%CI: 0.3-0.9; p=0.031) were significantly associated to OS in multivariate analysis. No difference was observed in terms of DCR, PFS, and OS in relation to age, histology, sex, line of vinorelbine therapy, or response to FL treatment. Hematological toxicity was acceptable, with grade 3/4 neutropenia occurring in 5 (8.4%) patients, and there were no cases of febrile neutropenia. The main non-hematological toxicities were grade 2 fatigue in 17 (28.8%) and constipation in 7 (11.8%) patients. Vinorelbine was moderately active in pemetrexed-pretreated MPM patients, with an acceptable toxicity profile, particularly in patients with ECOG-PS0 and FL-PFS ≥6 months.
    Lung cancer (Amsterdam, Netherlands) 11/2013; 84(3). DOI:10.1016/j.lungcan.2013.11.011 · 3.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes. Objectives Our objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials. Methods We searched PubMed for “mesothelioma” with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors. Measurements and main results We reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n = 137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review. Conclusion Response rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete responses to systemic therapies appear to be less common among patients with sarcomatoid tumors.
    Lung Cancer 09/2014; 86(2). DOI:10.1016/j.lungcan.2014.08.017 · 3.74 Impact Factor