Paclitaxel for malignant mesothelioma: a phase II study of the EORTC Lung Cancer Cooperative Group

University of Antwerp, Belgium.
British Journal of Cancer (Impact Factor: 4.84). 10/1996; 74(6):961-3. DOI: 10.1038/bjc.1996.465
Source: PubMed


The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma. Paclitaxel was given intravenously at a dose of 200 mg m-2 as a 3 h infusion every 3 weeks, after standard premedication with corticosteroids and antihistamines. This regimen was well tolerated, with < 4% of cycles resulting in severe toxicity. No major objective responses were observed and ten patients had stable disease. Median survival time was 39 weeks and the 1 year survival rate was 30%. In conclusion, paclitaxel at the dose and schedule investigated in this trial had no major activity in the treatment of malignant pleural mesothelioma.

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Available from: Nico van Zandwijk, Oct 03, 2015
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    • "At his last followup, 2 months after his last chemotherapy session, the patient was referred to our department with extensive ascites, despite the stable disease on the thorax. It was decided to initiate chemotherapy with carboplatin AUC 5.5 and docetaxel 100 mg/m 2 , not only based on our center's experience and clinical practice, but also based on previous published trials [28] [29] "
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    Case Reports in Medicine 07/2011; 2011:951732. DOI:10.1155/2011/951732
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    ABSTRACT: Malignant mesothelioma has a poor prognosis and is refractory to many agents. The antitumor effectiveness of cisplatin, paclitaxel, and suramin as single agents and in combination was evaluated in vivo against four lines of human pleural malignant mesothelioma xenografts in athymic nude mice, including one epithelial type and three fibrosarcomatous. After growth of tumors occurred by day 54 or 55, mice were randomized in groups of four each to receive either cisplatin 4 mg/kg intraperitoneally weekly x5, or paclitaxel (Taxol) 12.5 mg/kg subcutaneously daily 5 days/week for 3 consecutive weeks, or suramin 60 mg/kg intraperitoneally daily x4,versus controls treated with normal saline. Cisplatin was very effective against one line and also to a lesser degree against another line. Paclitaxel showed antitumor effects similar to cisplatin, being very effective in one line, and also showed good activity in another line. Suramin was basically inactive in all four lines. Following the results obtained with these single agents, it was decided to evaluate the combination of cisplatin and paclitaxel, which resulted in more pronounced antitumor effect in all four cell lines. These results indicate that the combination of cisplatin and paclitaxel is superior to each agent alone in this model, and that it deserves to be evaluated in patients with malignant mesothelioma.
    Journal of Surgical Oncology 03/1998; 67(2):104-11. DOI:10.1002/(SICI)1096-9098(199802)67:23.0.CO;2-E · 3.24 Impact Factor
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    ABSTRACT: BACKGROUND The purpose of this study was to assess the efficacy and toxicity of a combination of cisplatin and irinotecan (CPT-11) in the treatment of patients with malignant pleural mesothelioma and to characterize the pharmacokinetic profiles of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38).METHODS Fifteen previously untreated patients with malignant pleural mesothelioma were treated with cisplatin (60 mg/m2 on Day 1) and CPT-11 (60 mg/m2 on Days 1, 8, and 15) administered intravenously and followed by a 1-week rest period. The course of treatment was repeated every 28 days. After intravenous administration, the levels of CPT-11 and SN-38 in the plasma and pleural fluid were determined for each histologic subtype of mesothelioma.RESULTSAll patients were evaluable for response and toxicity. Four partial responses (response rate of 26.7%) with a median response duration of 25.9 weeks and 2 regressions of evaluable disease (overall response rate of 40%) were observed. The median survival time after chemotherapy was 28.3 weeks, and the median time to treatment failure was 22.1 weeks. The 1-year survival rate for all patients was 38.5%. Toxicity was well tolerated, and there were no treatment-related deaths. World Health Organization Grade 3 leukopenia occurred in 3 patients (20%), and Grade 1 or 2 diarrhea occurred in 3 patients (20%). There was no excess toxicity in patients with large pleural effusions compared with those with no pleural effusions. CPT-11 and SN-38 were detected in the pleural fluid 1 hour after intravenous administration. The maximum concentrations of CPT-11 and SN-38 in the pleural fluid were 36.5% and 75.8%, respectively, of the corresponding plasma values.CONCLUSIONS The combination of cisplatin and CPT-11 had definite activity against malignant pleural mesothelioma and was well tolerated. The intravenous administration of CPT-11 produced adequate distribution of CPT-11 and its active metabolite SN-38 into the pleural fluid and allowed a higher concentration of the more active SN-38 to make contact with mesothelioma cells in the thoracic cavity. These results warrant further clinical evaluation of this combination chemotherapy for the treatment of malignant pleural mesothelioma in a confirmatory Phase II trial. Cancer 1999;85:2375–84. © 1999 American Cancer Society.
    Cancer 06/1999; 85(11):2375 - 2384. DOI:10.1002/(SICI)1097-0142(19990601)85:11<2375::AID-CNCR12>3.0.CO;2-E · 4.89 Impact Factor
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