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

Department Oncology, Finsen Centre/National University Hospital, 9 Blegdamsvej, Copenhagen DK-2100, Denmark.
British Journal of Cancer (Impact Factor: 4.84). 08/2008; 99(1):44-50. DOI: 10.1038/sj.bjc.6604421
Source: PubMed


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.

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Available from: Jens Benn Sørensen, May 22, 2014
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    • "Because of pemetrexed costs is difficult for patients to have it as a standard care. Combinations of cisplatin with other effective drugs (vinorelbine, gemcitabine) have not, to our knowledge, been studied in phase III trials (Sorensen et al, 2008). Doxorubicin have shown efficacy against mesothelioma (Antman, 1980). "
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    ABSTRACT: Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as (99m)Tc-LD distribution in MPM lesions after chemotherapy administration. A total of 38 patients with non-resectable MPM received LD 40 mg m(-2) and cisplatin 60 mg m(-2) every 21 days. Gamma camera images of (99m)Tc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028). In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4-5.9 months), and median overall survival (OS) was 19.6 months (15.2-37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001). The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. (99m)Tc-LD showed higher levels of tumour uptake as compared with surrounding tissues.
    British Journal of Cancer 02/2012; 106(6):1027-32. DOI:10.1038/bjc.2012.44 · 4.84 Impact Factor
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    • "In a 63-patient trial in the second-line setting, a response rate of 16% and a median survival of 9.6 months were achieved [34]. The combination of vinorelbine with cisplatin yielded a response rate of 29.6% and a median survival of 16.8 months [35]. "
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    ABSTRACT: Opinion statementSystemic therapy is the only treatment option for the majority of mesothelioma patients, for whom age, co-morbid medical illnesses, non-epithelial histology, and locally advanced disease often preclude surgery. For many years, chemotherapy had a minimal impact on the natural history of this cancer, engendering considerable nihilism. Countless drugs were evaluated, most of which achieved response rates below 20% and median survival of <1 year. Several factors have hampered the evaluation of systemic regimens in patients with mesothelioma. The disease is uncommon, affecting only about 2500 Americans annually. Thus, most clinical trials are small, and randomized studies are challenging to accrue. There is significant heterogeneity within the patient populations of these small trials, for several reasons. Since all of the staging systems for mesothelioma are surgically based, it is almost impossible to accurately determine the stage of a patient who has not been resected. Patients with very early stage disease may be lumped together with far more advanced patients in the same study. The disease itself is heterogenous, with many different prognostic factors, most notably three pathologic subtypes—epithelial, sarcomatoid, and biphasic—that have different natural histories, and varying responses to treatment. Finally, response assessment is problematic, since pleural-based lesions are difficult to measure accurately and reproducibly. Assessment criteria often vary between trials, making some cross-trial comparisons difficult to interpret. Despite these limitations, in recent years, there has been a surge of optimism regarding systemic treatment of this disease. Several cytotoxic agents have been shown to generate reproducible responses, improve quality of life, or prolong survival in mesothelioma. Drugs with single-agent activity include pemetrexed, raltitrexed, vinorelbine, and vinflunine. The addition of pemetrexed or raltitrexed to cisplatin prolongs survival. The addition of cisplatin to pemetrexed, raltitrexed, gemcitabine, irinotecan, or vinorelbine improves response rate. The combination of pemetrexed plus cisplatin is considered the benchmark front-line regimen for this disease, based on a phase III trial in 456 patients that yielded a response rate of 41% and a median survival of 12.1 months. Vitamin supplementation with folic acid is essential to decrease toxicity, though recent data suggests that there may be an optimum dose of folic acid that should be administered; higher doses may diminish the effectiveness of pemetrexed. There are also several unresolved questions about the duration and timing of treatment with pemetrexed that are the subject of planned clinical trials. It is essential to recognize that the improvements observed with the pemetrexed/cisplatin combination, though real, are still modest. Other active drugs or drug combinations may be more appropriate for specific individuals, and further research is still needed to improve upon these results. Since the majority of mesotheliomas in the United States occur in the elderly, non-cisplatin-containing pemetrexed combinations may be more appropriate for some patients. Now that effective agents have been developed for initial treatment, several classical cytotoxic drugs and many novel agents are being evaluated in the second-line setting. These include drugs targeted against the epidermal growth factor, platelet-derived growth factor, vascular endothelial growth factor, src kinase, histone deacetylase, the proteasome, and mesothelin. Given the progress made in recent years, there is reason to believe that more effective treatments will continue to be developed.
    Current Treatment Options in Oncology 09/2008; 9(2-3):171-9. DOI:10.1007/s11864-008-0071-3 · 3.24 Impact Factor
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    ABSTRACT: Die Chemotherapie ist essenzieller Bestandteil sowohl kurativer als auch palliativer Behandlungskonzepte beim malignen Pleuramesotheliom (MPM). Bei der Mehrzahl der Patienten sind aufgrund des Ausbreitungsgrads der Erkrankung, ihres Alters bzw. vorhandener Komorbiditäten nur palliative Behandlungsoptionen möglich. Standard in der Erstlinientherapie ist die Kombination von Pemetrexed und Cisplatin, die zu einer signifikanten Verlängerung des Überlebens sowie zur Verbesserung der Lebensqualität bei gebesserter Lungenfunktion und tumorbedingter Symptome führt. Mit zunehmender Detektion molekularer Besonderheiten des MPM wächst die Zahl zielgerichteter Substanzen, die erfolgversprechend in Studien geprüft werden. Die Strahlentherapie spielt in der palliativen Behandlung des MPM eine untergeordnete Rolle. Der Stellenwert einer prophylaktischen Stich- oder Drainagekanalbestrahlung ist nicht geklärt. Die Talkumpleurodese zur Beseitigung ausgedehnter, rezidivierender Pleuraergüsse und eine kombinierte analgetische Behandlung sind feste Bestandteile des palliativen Managements beim MPM. Dieser Artikel gibt einen Überblick über Standards in der medikamentösen, insbesondere der palliativen systemischen Therapie des MPM, neue Substanzen und symptomorientierte Behandlungsoptionen. Chemotherapy is an essential part not only for curative but also for palliative treatment concepts for malignant pleural mesothelioma (MPM). For the majority of patients with MPM palliative forms of treatment are the only option due to the extent of the disease, their age or the presence of comorbidities. The standard first line chemotherapy is the combination of pemetrexed and cisplatin which not only leads to a significant extension of survival but also to an improvement of quality of life with better lung function and reduction of tumor-linked symptoms. With increasing detection of molecular characteristics of MPM the number of targeted agents increases which show promising results in trials. Radiotherapy plays a subordinate role in the palliative treatment of MPM. The significance of prophylactic radiation of puncture or drainage canals has not been clarified. Talc pleurodesis for the elimination of extensive, relapsing pleural effusion and a combined analgetic treatment are integral components of the palliative management of MPM. This article provides an overview of standards in medicinal, especially palliative systematic therapy of MPM, new substances and symptom-oriented treatment options.
    Der Pneumologe 01/2009; 7(1):36-42. DOI:10.1007/s10405-009-0351-z
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