Hesdorffer ME, Chabot J, DeRosa C, Taub R.

Mesothelioma Applied Research Foundation, Santa Barbara, CA, USA. mhesdorer@curemeso.org

Abstract

Opinion statement: Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that rapidly spreads within the confines of the abdominal cavity to involve most accessible peritoneal and omental surfaces. Current treatment options are unsatisfactory, and new approaches are needed. Recent publications have reported improved survival with an intensive loco-regional treatment strategy including cytoreductive surgery (CRS) along with hyperthermic intraperitoneal chemotherapy (HIPEC). We have noted at our institution prolonged survival in selected patients after intensive multimodality treatment. Our most recently reported trial included initial laparatomy with omentectomy, resection of peritoneal implants, and placement of bilateral peritoneal Portacath; repeated courses of intraperitoneal chemotherapy with doxorubicin, cisplatin, and interferon gamma; second-look laparotomy; and intraoperative hyperthermic perfusion with mitomycin and cisplatin, followed by whole abdominal radiation. To date there have been no universally accepted treatments for MPM. Unless referred to a specialty center, patients are routinely treated with pemetrexed and cisplatin which has been shown to increase survival in pleural mesothelioma.

Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, Nicholson AG, O’Brien M, Peake M, Rudd R, Snee M, Steele J, Girling DJ, Nankivell M, Pugh C, Parmar MK; on behalf of the MS01 Trial Management Group.

Leeds General Infirmary, Leeds, UK.

Abstract

Background: Malignant pleural mesothelioma is almost always fatal, and few treatment options are available. Although active symptom control (ASC) has been recommended for the management of this disease, no consensus exists for the role of chemotherapy. We investigated whether the addition of chemotherapy to ASC improved survival and quality of life.

Methods: 409 patients with malignant pleural mesothelioma, from 76 centres in the UK and two in Australia, were randomly assigned to ASC alone (treatment could include steroids, analgesic drugs, bronchodilators, palliative radiotherapy [n=136]); to ASC plus MVP (four cycles of mitomycin 6 mg/m(2), vinblastine 6 mg/m(2), and cisplatin 50 mg/m(2) every 3 weeks [n=137]); or to ASC plus vinorelbine (one injection of vinorelbine 30 mg/m(2) every week for 12 weeks [n=136]). Randomisation was done by minimisation, with stratification for WHO performance status, histology, and centre. Follow-up was every 3 weeks to 21 weeks after randomisation, and every 8 weeks thereafter. Because of slow accrual, the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival. Analysis was by intention to treat. This study is registered, number ISRCTN54469112.

Findings: At the time of analysis, 393 (96%) patients had died (ASC 132 [97%], ASC plus MVP 132 [96%], ASC plus vinorelbine 129 [95%]). Compared with ASC alone, we noted a small, non-significant survival benefit for ASC plus chemotherapy (hazard ratio [HR] 0.89 [95% CI 0.72-1.10]; p=0.29). Median survival was 7.6 months in the ASC alone group and 8.5 months in the ASC plus chemotherapy group. Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone (HR 0.80 [0.63-1.02]; p=0.08), with a median survival of 9.5 months. There was no evidence of a survival benefit with ASC plus MVP (HR 0.99 [0.78-1.27]; p=0.95). We observed no between-group differences in four predefined quality-of-life subscales (physical functioning, pain, dyspnoea, and global health status) at any of the assessments in the first 6 months.

Interpretation: The addition of chemotherapy to ASC offers no significant benefits in terms of overall survival or quality of life. However, exploratory analyses suggested that vinorelbine merits further investigation.

Cordony A, Le Reun C, Smala A, Symanowski JT, Watkins J.

M-TAG Pty Ltd, A Unit of IMS Health, St Leonards, NSW, Australia. acordony@au.imshealth.com

Abstract

Objectives: Findings from the largest randomized phase III trial in patients with unresectable malignant pleural mesothelioma (EMPHACIS study; n = 448) were used to examine the cost-effectiveness of pemetrexed plus cisplatin therapy versus cisplatin monotherapy in patients with the disease. The cost-effectiveness of pemetrexed/cisplatin versus alternative treatments was also examined.

Methods: Two cost-effectiveness analyses were designed to model best survival outcome over time for a number of patient cohorts. First, trial-based patient-level data were utilized and resource use was costed for the study arm and comparator. A second cost-effectiveness analysis then compared the mean costs and outcomes associated with pemetrexed/cisplatin with the most commonly used (unlicensed) regimens in the United Kingdom—mitomycin-C, vinblastine, and cisplatin (MVP); vinorelbine; and active symptom control—using trial-based data and data extrapolated from a review of the literature.

Results: The total pemetrexed/cisplatin cost per patient varied between £8779 and £9020 for all cohorts studied in model 1. Average life-years gained per patient were between 0.20 and 0.28. Quality-adjusted life-years, based on mean and median survival, ranged from 0.13 to 0.31. Incremental cost per life-year gained and quality-adjusted life-year ratios, using both mean and median survival, ranged from £20,475 to £68,598. The second cost-effectiveness analysis resulted in ratios ranging from £14,595 to £32,066.

Conclusions: Pemetrexed/cisplatin demonstrated acceptable cost-effectiveness when compared with cisplatin monotherapy and alternative treatments commonly used in UK clinical practice.

Abstract

Purpose: To evaluate transpulmonary chemoembolization (TPCE) as a symptomatic palliative method for treating inoperable primary lung tumors.

Materials and Method: From 2002 to 2005, 17 patients (17 males, 3 females; average age: 64.5 years) suffering from primary lung tumors were treated in 3.6 sessions (range: 2 to 8) using TPCE. The patients had the following primary tumors: adenocarcinoma (n = 6), pleural mesothelioma (n = 2), squamous cell carcinoma (n = 1), small cell carcinoma (n = 1), and non-small cell carcinoma (n = 7). After femoral vein puncture, tumor-supplying pulmonary arteries were selectively explored, and 5 – 10 mg mitomycin C and 5 – 10 mL lipiodol and microsphere particles (Spherex) (20 – 70 µm in diameter) were applied with balloon protection. Diagnosis and follow-up were performed in 4-week intervals with unenhanced and contrast-enhanced computed tomography (CT). The mean follow-up was 11.3 months.

Results: Treatment
was well tolerated by all patients with no major side effects or complications. The laboratory parameters were not significantly influenced. 11.8 % of the patients (n = 2) showed high or moderate lipiodol uptake, and 76.5 % (n = 13) showed low lipiodol uptake. After evaluation of morphologic criteria, a mean volume regression of 12.1 ml (40.4 %) of the embolized areas was achieved in four patients (23.5 %), while a constant value was identified during follow-up for seven patients (41.2 %). In six patients (35.3 %), progression of the treated lung tumors was recorded. The tumor increased by a mean of 38.37 ml (165.38 %).

Conclusion: TPCE is a well-tolerated palliative treatment option for patients with primary lung tumors.

Keywords: chemoembolization, lung tumors, palliative measures

Guadagni S, Clementi M, Valenti M, Fiorentini G, Cantore M, Kanavos E, Amicucci G.

Department of Surgical Sciences, University of L’Aquila, Italy. stefanoguadagni@interfree.it

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive treatment-resistant tumor with a median survival from diagnosis of 12 months. Although multimodality protocols that combine aggressive surgery and adjuvant chemotherapy or radiotherapy have shown improved survival in selected cases, the majority of patients with MPM are not suitable for radical surgery due to advanced stage and comorbid medical illness. For these patients combination chemotherapy with Pemetrex and Cisplatin should be considered for first line palliative chemotherapy. The therapeutic options available to patients with MPM resistant or refractory to systemic chemotherapy are very limited. Thoracic “stop-flow” perfusion (TSP) is a semi-invasive loco-regional drug delivery system that, limiting the circulation to the thorax during the anticancer agent’s infusion, claims the advantage of reaching high drug concentration at the tumor site while maintaining a low systemic toxicity. The aim of this phase I-II study was to evaluate the toxicity profile and efficacy of two different platinum-based combined regimens–cisplatin plus mitomycin-C (MMC) and cisplatin plus melphalan (L-PAM)–administered using TSP technique in patients with advanced or recurrent MPM who had refractory disease after systemic first line chemotherapy. Patients with histologically proven unresectable stage II-III MPM entered this trial. Between January 1995 and December 2001, 27 patients were enrolled in the study and submitted to TSP using the two different chemotherapy cisplatin based regimens: 12 patients received cisplatin 100 mg/m2 plus MMC 20 mg/m2 (MMC arm) and 15 cisplatin 100 mg/m2 plus L-PAM 50 mg/m2 (L-PAM arm). Objective responses were assessed by CT-scan 30 and 60 days after the end of treatment in all 27 enrolled patients. Two patients (7.4%) achieved a complete response, 2 (7.4%) a partial response and 4 (14.8%) a minor response. The remaining 19 patients (70.3%) showed a stable disease. No patients developed progression of the disease following the first TSP. The overall median time to progression was 8.9 months (range 1-41). The median survival time for all patients from the beginning of regional chemotherapy was 16.6 months, with a 1-year survival rate of 62.9%, a 2-year survival rate of 18.5%, and a 3-year survival rate of 7.4%. Our data show that TSP is a relatively effective second-line treatment in patients with progressive disease after systemic chemotherapy, with a low rate of major complications and treatment-related toxicity.

Fennell DA, Steele JP, Shamash J, Evans MT, Wells P, Sheaff MT, Rudd RM, Stebbing J.

Lung and Mesothelioma Unit, Department of Medical Oncology, St Bartholomew’s Hospital, West Smithfield, London, UK.

Abstract

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.

Keywords: mesothelioma, irinotecan, cisplatin, mitomycin C, phase II, first-line, recurrence