Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0–2. Treatment was vinorelbine 25 mg m−2 i.v. weekly and cisplatin 100 mg m−2 i.v. every 4 weeks with hydration and standard prophylactic antiemetic treatment. Patients gave written informed consent. Characteristics of 54 consecutive patients were: males 85%, epithelial subtype 74%, IMIG stages III and IV 35 and 46%, performance status 0, 1, and 2, 26, 69, and 6%, and median age 63 years (31–78 years). CTC grade 3 or 4 toxicity occurred with respect to leukocytopenia (48% of patients, grade 4 in 13%), nausea (13%), neurotoxicity (11%), nephrotoxicity (4%), and other toxicities (9%). There were no toxic deaths. The median number of cycles was four. The fraction of patients alive at 1-, 2-, and 3-years were 61, 31, and 4%, respectively, and median survival and median time to progression were 16.8 months (0.5 to 46.4 +months) and 7.2 months (1.6 to 40.6 + months). There were two CRs and 14 PRs (response rate 29.6%). Cisplatin and intravenous vinorelbine is a highly active regimen in MPM with a response rate and survival comparable to the most active regimens so far reported

Apoptosis Induced by Piroxicam plus Cisplatin Combined Treatment Is Triggered by p21 in Mesothelioma

BACKGROUND: Malignant mesothelioma (MM) is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing. CONCLUSIONS/SIGNIFICANCE: Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21

Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): Feasibility and results

BACKGROUND: Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma (MPM). A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy. Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM. The aim of our study was to evaluate the feasibility of this protocol and to estimate survival. METHODS: From 2000 to 2003, 21 patients with MPM (14 males and 7 females, median age 59 years) were enrolled in the prospective study. Induction chemotherapy consisted of Carboplatin (AUC 5mg/mL/min on Day 1) and Gemcitabine (1000mg/m(2) on Days 1, 8, 15) for three to four cycles. EPP was performed 3-5 weeks after induction therapy, while post-operative RT was given 4-6 weeks after operation. RESULTS: Ten patients received three cycles of chemotherapy, 10 patients received four cycles and 1 patient had two cycles. Grades 3-4 haematological toxicity occurred in eight (38.1%) patients. Chemotherapy response rate was: complete 0%, partial 33.3% and stable disease 66.7%. Seventeen (80.9%) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4%. Median survival was 25.5 months, with an overall 1, 3 and 5-year survival rate of 71, 33 and 19%, respectively. CONCLUSIONS: In MPM, the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible, with good results in terms of survival and morbidity. Our results are similar to those of other studies using a heavier modality treatment

Effect of induction chemotherapy on lung function and exercise capacity in patients affected by malignant pleural mesothelioma

Objectives: The effect of induction chemotherapy (IC) on lung function and exercise capacity in patients with malignant pleural mesothelioma (MPM) has not been largely examined. The aim of this study was to evaluate the changes in pulmonary function and oxygen consumption following IC in patients with MPM. Methods: Between 2004 and 2009, 36 consecutive patients (mean age 62.1 \ub1 1.5 years, M/F = 25/11) were prospectively investigated. Data concerning medical history, histology, staging and response to chemotherapy were collected. All patients underwent pulmonary function test before (in the absence of pleural effusion) and after chemotherapy (platinum-based agent plus pemetrexed); 23 out of 36 patients also performed a cardiopulmonary incremental exercise test. Results: An epithelioid histotype was documented in 88.8% of patients. A partial response to chemotherapy was observed in 44.5% of cases and 36.1% of patients experienced grade 2\u20133 toxicity. A significant improvement in forced expiratory volume in 1 s (FEV1) (0.13 \ub1 0.30 l; P = 0.01), in VO2 peak (1.76 \ub1 2.91 ml kg 121 min 121; P = 0.005), in PaO2 at rest (4.76 \ub1 9.84 mmHg; P = 0.03) and in PaO2 at peak exercise (6.26 \ub1 12.72 mmHg; P = 0.04) was detected. The diffusion capacity of the lung for carbon monoxide (DLCO) also increased (1.25 \ub1 4.68 ml min 121 mmHg 121), although not significantly (P = 0.20). The stratified analysis based on the response to IC showed a significant improvement in FEV1, forced vital capacity (FVC) and vital capacity (VC) (both absolute and percentage of predicted values) only in patients with a partial response. Conclusions: An improvement in lung function and exercise capacity was seen after IC in patients with MPM. These data suggest that IC does not compromise cardiopulmonary performance in this subset of patients